Category Archives: Cell Therapy

Investigators identified that in pivotal clinical trials supporting FDA approvals of CAR T-cell therapies for patients with hematologic cancer, Black patients were significantly underrepresented.

Notable disparities with regard to Black patients have been observed in CAR T-cell therapy clinical trials that have led to FDA approvals in hematologic cancers, according to findings from a study published in JAMA Network Open.1

Between studies, about 2% to 5% of Black patients were enrolled in clinical trials, received CAR T therapies, and reported efficacy. Using an adjusted prevalence measure, investigators reported that the lowest participation to prevalence ratio was 0.2 for multiple myeloma and 0.6 for large B-cell lymphoma (LBCL). The lowest number of Black patients was observed in the clinical trial that led to the approval of brexucabtagene autoleucel (Tecartus) in mantle cell lymphoma, with only 1 Black patient included.

The findings of this study suggest that low enrollment of Black persons exists in trials for CAR T therapy and that the disparity is substantial and ongoing, especially for therapies to treat [multiple myeloma]. Efforts should be made to understand and overcome barriers that lead to decreased enrollment of Black participants in clinical trials that include novel, potentially beneficial, and/or curative CAR T therapies in difficult-to-treat hematological malignant neoplasms with otherwise limited treatment options, Samer Al Hadidi, MD, assistant professor of medicine at the University of Arkansas for Medical Sciences, said in a press release.2

Between August 2017 and March 2021, 5 CAR T products were approved across 7 indications. A total of 1057 patients were enrolled, 746 of whom received CAR T-cell therapies and 729 reported efficacy.

In the study that led to the approval of tisagenlecleucel (Kymriah) in acute lymphoblastic leukemia, patients who were Black were put in a racial category designated as other, otherwise, their enrollment was specified mainly in the demographic subgroups information available under the FDA product labeling information.

Investigators noted that most of the studies included in FDA approvals did not report the proportions of racial and ethnic groups. Eighteen Black patients with diffuse LBCL who were treated with CAR T-cell therapy reported efficacy per disease category. Additionally, in one CAR T-cell therapy approval study for multiple myeloma, only 6 Black patients participated, comprising 6% of the total patient population.

The incidence of [multiple myeloma] is more than 2 times higher among Black persons than among non-Hispanic White persons, the investigators wrote. Black patients with [multiple myeloma] face multiple disparities, including lower use of hematopoietic stem cell transplantation, palliative care, and novel therapeutics, which may result in worse outcomes. Lack of access to novel therapies that disproportionately affect Black persons may result in further widening of the existing established disparities.

On April 13, 2022, the FDA initiated a plan to increase clinical trial diversity by employing the Race and Ethnic Diversity Plan.3 This has gone into effect for companies submitting applications for investigational new drugs, biologics license application, or investigation device exemption. This new plan recommends that companies define their enrollment goals for underrepresented populations so that they may be a part of pre-specified protocol objectives.

Read more:
Dearth of Participation From Black Patients Noted in CAR T Clinical Trials Supporting FDA Approvals - Cancer Network

Investigators of the phase 1/2 IMAGINE study (NCT05138458), evaluating MT-101 in patients with refractory or relapsed peripheral T-cell lymphoma (PTCL), have dosed its first patient, according to Myeloid Therapeutics Inc.

MT-101 is made with myeloid cells collected from the patient's blood which are then modified and later infused back into the patients veins. The modified myeloid cells are able to recognize the tumor cells and are designed to target and kill them.

The agent targeting the surface receptor, CD5, is the first mRNA engineered chimeric antigen receptor (CAR) monocyte (CAR-M) created by the company's proprietary ATAK platform. The ATAK CAR is designed to specifically promote broad anti-tumor activity.

"We are pleased to announce the initiation of dosing in the IMAGINE clinical trial, which represents a major milestone in our efforts to provide treatment with CD5 ATAK cells for patients with relapsed or refractory PTCL," said Michele Gerber, MD, MPH, chief medical officer of Myeloid, in a press release. "Currently, we are continuing through the dose-escalation cohorts of IMAGINE, which [are] designed to assess the safety and tolerability, optimal dose regimen, tumor penetration and preliminary efficacy of MT-101 in patients with PTCL. Following the conclusion of phase 1, we expect to expand quickly into the phase 2 portion of this study, which we designed to support registration of MT-101."

This open-label, first-in-human, multiple-ascending dose, multicenter, phase 1/2 study looks to test the safety, tolerability, and efficacy of MT-101 in patients with PTCL.

The research study is divided into 2 parts with the first looking to determine the safety and tolerability of the study drug product. Throughout this portion of the study, 3 groups of study patients will be examined with the first group receiving a low dose of cells, the second group receiving a higher dose of cells, and the third group receiving the higher dose of cells and lymphodepleting chemotherapy in order to reduce the number of T cells that are in the blood. The second part of the study will then administer cells with or without chemotherapy based on results of part 1. Safety, tolerability, and efficacy of MT-101 will be assessed within this portion of the study, and all patient groups will receive 6 doses of drug product over 3 weeks.

Enrollment is open to adults aged 18 and older with refractory or relapsed pathologically confirmed PTCL. Patients must have a CD5-expressing tumor by IHC or flow cytometry of tumor biopsy within 3 months of or at the time of screening, an ECOG performance status of 2 or less, and adequate organ function.

The primary end point is examining the safety and tolerability of MT-101, with secondary end points including MT-101 cell kinetics in blood and objective response rate. Other outcome measures of the trial consist of duration of response, progression-free survival, and overall survival.

According to the press release, at day 28, which is the primary end point for safety and tolerability, the dosed patient showed no dose-limiting toxicities, no cytokine release syndrome, and no immune effector cell-associated neurotoxicity syndrome. Additionally, the company achieved a reduced vein-to-vein time of 8 days with the dosing of this patient.

Currently, the dose-escalation portion of this study is open and enrolling patients. When the recommended phase 2 dose is found, a phase 2 trial will be initiated to support registration in this patient population.

"MT-101, Myeloid's leading mRNA-engineered monocyte, was advanced from conception and preclinical proof of concept to our first dose in humans in just 18 months. Importantly, this is the first instance of an engineered monocyte cell product delivered to a patient with a significantly reduced vein-to-vein time of just 8 days," stated Daniel Getts, PhD, chief executive officer of Myeloid, in the release. "Overall, this achievement highlights Myeloid's ability to produce scalable cell therapy products in an efficient manner, and we are optimistic about the impact this program can provide to PTCL patients and their families going forward."

Read more from the original source:
First Patient Dosed in IMAGINE Trial Evaluating MT-101 in Patients With PTCL - Targeted Oncology

With the recent FDA approvals of belantamab mafodotin (BLENREP), ciltacabtaene autoleucel (cilta-cel; Carvykti), and idecabtagene vicleucel (ide-cel; Abecma), the multiple myeloma treatment landscape is hub for BCMA-directed therapies.

Each of the FDA-approved BCMA-directed therapies, and targets are being explored in ongoing studies examining response rates in patients with or without prior BCMA-directed CAR T-cell therapy.

The BCMA CAR products currently approved for patients with myeloma are specifically for those who have had at least 4 prior lines of therapy, including a proteasome inhibitor image and a CD38 antibody. While there is no age limit, patients should be in good enough condition to withstand cytokine release syndrome and are typically those without advanced heart failure, uncontrolled cardiac conditions, oxygen independence, or other severe pulmonary conditions.

During the 3rd Summit of the Americas on Immunotherapies for Hematologic Malignancies, Adam Cohen, MD, director, Myeloma Immunotherapy, and associate professor of Medicine at the Hospital of the University of Pennsylvania, presented clinical data supporting the approved agents. He noted the positive findings of the exciting new immunotherapies for myeloma which have shown high response rates, even in patients who have had prior BCMA-directed CAR T cells.

In an interview with Targeted OncologyTM, Cohen further discussed the recent updates and advancements in BCMA-directed therapies for multiple myeloma.

TARGETED ONCOLOGY: Can you discuss your presentation on the topic of BCMA-directed therapies for patients with multiple myeloma?

Cohen: The bulk of my talk is presenting the clinical data that supports the use of both belantamab mafodotin, as well as ide-cel, and cilta-cel, which are FDA approved products. I also go through some of the exciting data coming out with the bispecific antibodies and other immune therapy that's showing a lot of promise in myeloma as well as in other cancers.

I reviewed some of the most mature data from the BCMA-targeted bispecifics as well as from 2 bispecifics hitting other targets, 1 called GPRC5D and 1 [called] FCRH5. So, there's really a lot of exciting new immunotherapies for myeloma, and these are showing high response rates, even in patients who have already had prior CAR T cells or prior BCMA-directed therapy in some cases.

Then, I finished up with a little bit of discussion of correlative analysis trying to understand mechanisms of resistance, which patients might be likely to respond, and which patients might not. I think that's going to hopefully help frame the next generation of trials if we really understand why some patients are not going to respond to these current products that are either better products that we can use, or can we combine these currently available therapies with some of our other therapies in myeloma to really start getting deeper and more durable remissions for more patients and maybe even eventually get to a cure? That's really what we're all hoping [for].

What survival response rates are being seen with other therapies for this disease?

Unfortunately, once patients had become refractory to some of our standard upfront treatments, proteasome inhibitors, IMiDs and CD-38 antibodies, we know that relapse in that relapsed refractory population, that response rates, PFS, and survivals are fairly poor. There was a large study called the MAMMOTH study that was a retrospective look back at multiple different regimens from multiple centers. Regardless of the regimen, the response rates were somewhere in the order of 30%, the PFS was only 3 to 4 months, and survival was generally in the order of 6 to 8 months. It really was an area of unmet need, and fortunately, the BCMA targeted therapies are trying to fill that niche.

Can you discuss some of the FDA approved agents? What was exciting about the study supporting these approvals?

The first BCMA-targeted drug that was approved was called belantamab mafodotin. This is an anti-BCMA antibody drug conjugate. It's a monoclonal antibody that has a microtubule poison on the end of it called MMAF, and it's given as an IV infusion every 3 weeks. It was approved based on the DREAMM-2 study which looked at 2 different doses of the drug and found that the 2.5 milligram per kilogram dose was sort of the optimal one going forward, and that's the one that got approved.

The response rate, again in that heavily refractory population of a median 6-7 prior lines of therapy was around 32%. Median PFS was only about 3 months, but the median duration of response was 11 months, meaning if you did get a response, those responses tended to be fairly durable. We've had patients on this drug going on more than 2 and a half years. So that's the first one that got approved in 2020.

The next one that was approved was ide-cel, which is a CAR T-cell product targeting BCMA, which was approved in the summer of 2021. This was based on the KARMA study, which was a multi-institution, single-arm, phase 2 study giving these BCMA-targeted CAR T cells to patients with heavily refractory myeloma. In that study, the overall response rate was 73%, with almost 40% of patients getting a CR [complete response]. The median progression-free survival for all patients was around 9 months, but in the group that got the highest dose of 450 million cells, which is the target dose approved by the FDA, median PFS was close to 12 months. This was unprecedented activity in this heavily pretreated population of patients.

The final product, that just got approved at the end of February 2022, is cilta-cel. This is another CAR T-cell product targeting BCMA. It has a distinct CAR construct compared with ide-cel cell and was also tested in a multi-institution. phase 2 study in the United States called CARTITUDE-1. In this study at 97 patients, the overall response rate was 98% with over 80% of patients achieving a complete remission. Median progression-free survival has not yet been reached with about 2 years of follow up. There are remarkable response rates, depth of response, and PFS with these CAR T-cell products in particular. I think that's what's generating a lot of excitement in the field right now, and now we have 2 different CAR products that are approved and available for our patients, which is great.

Are there currently any concerns with using BCMA-directed therapies?

Each of these approaches have their own toxicities that we need to watch out for. Belantamab, which is the antibody drug conjugate, shows one of the primary toxicities is corneal toxicity, keratopathy. The MMAF chemotherapy agent can lead to epithelial damage in the cornea that can cause blurred vision or dry eye. This is reversible, if you hold the drug and let it wash out, it does resolve and there's no permanent visual loss. It does require co-management with an eye care specialist, either an ophthalmologist or optometrist, to do eye exams and does require some dose modifications and dose holds in order to get patients through this. That's the one thing for the belantamab to keep an eye out for.

The main risks with the CAR T-cell products are similar to CAR T cells for other diseases, namely cytokine release syndrome and neurotoxicity. This tends to occur within the first week of treatment. Patients are typically hospitalized either during the CAR infusion, or shortly thereafter for monitoring for this. We've learned how to really manage these with aggressive, supportive care, and in some cases, tocilizumab or steroids to try to minimize the risk of these becoming severe. That's something we definitely need to keep an eye out for, with the CAR T-cell products, at least in the immediate post treatment period.

I think the key thing that we're learning is that these certainly can be very immune suppressive. Targeting BCMA can lead to hypogammaglobulinemia and increased risk of infections that can persist for months. These patients often need IVIG replacement, they need to be monitored closely with prophylactic antimicrobials as needed, and prompt treatment of any signs of infection.

Who is the ideal candidate for this type of treatment? What advice do you have for oncologists whose patient may not be the ideal candidate?

Right now, both BCMA CAR products in myeloma are approved for patients who have had at least 4 prior lines of therapy, which must include a proteasome inhibitor image and a CD38 antibody. There's no real upper age limit for CAR T-cell therapy. We've treated patients in their early 80s, but they do need to be robust to be able to withstand cytokine release syndrome. Typically, we would exclude patients with advanced heart failure or uncontrolled cardiac conditions, oxygen independence, COPD, or other severe pulmonary conditions or very poor performance status. We don't think renal failure necessarily is an exclusion, they were excluded from the trials, but we have been able to treat patients with commercial products even with profound renal dysfunction, just modifying the lymphodepleting chemotherapy.

I think the time to think about sending your patient into the CAR T-cell center should be when they're progressing on their third line therapy and you're thinking about starting a fourth line treatment. It would be helpful if you're thinking there would be a CAR T-cell candidate to get them into the center so we can assess them at the same time and add them to the waitlist for CAR T cells. Unfortunately, there's still limited manufacturing slots for these, so there can be a several month waitlist. That way, that patient is already in the system and if they don't respond to fourth-line treatment, or even if they are responding well but it's not a deep response, we may be able to take them to CAR T cells while they're under good disease control.

We're learning that patients who are really progressing rapidly while we're trying to collect T cells and then manage them with bridging therapy during the manufacturing process has been challenging. Some of those patients unfortunately never make it to their CAR T cells because their disease just takes off. I think it's better to send them in while they're still under some control and while we have good bridging options.

See the rest here:
Increasing Use of BCMA-Directed Therapies in Multiple Myeloma - Targeted Oncology

Company Logo

Global Microcarrier Market

Global Microcarrier Market

Dublin, May 11, 2022 (GLOBE NEWSWIRE) -- The "Global Microcarrier Market, Size, Share, Forecast 2022-2027, Industry Trends, Growth, Impact of COVID-19, Opportunity Company Analysis" report has been added to ResearchAndMarkets.com's offering.

This report provides a detailed analysis of Microcarriers Industry. The global microcarrier market is estimated to reach US$ 2.24 Billion by 2027, from S$ 1.48 Billion in 2021.

Globally, a microcarrier is a non-toxic finely particulate material used to grow cells in a suspension or a support matrix, which facilitates the growth of adherent cells in a bioreactor. Recently, microcarrier-based cell culture has attracted significant attention from scientists and technologists worldwide. Besides, microcarrier technology has advantages for producing significant numbers of functional cells and maintaining their unique phenotypes as a powerful source of cell therapy and tissue engineering. With improved microcarrier materials, especially purely natural-material microcarriers, tissue engineering has a bright future.

Global Microcarrier Is Expected to Expand at a CAGR of 7.1% During 2021-2027:

Over the years, factors such as the increasing incidence of diseases demanding cell therapy and boosting R&D funding by research institutes and biopharmaceutical companies have played a critical role in market expansion. Further, the rising demand for monoclonal antibodies for the targeted treatment of cancer and other chronic disorders is expected to create significant opportunities for market growth during the forecast period. In addition, the increasing prevalence of cancer cases is playing an essential role in developing the microcarrier market. Also, the growing demand for cell-based vaccines is fuelling the market's growth over the forecast period.

COVID-19 Is Anticipated to Have a Noteworthy Impact On the Microcarrier Market:

In our report, we have closely observed the impact of COVID-19 on the global microcarrier market. After WHO officially announced COVID-19 as a pandemic, several renowned pharmaceutical companies, research institutes, and start-ups geared their R&D efforts to devise drugs and vaccines for infectious diseases. Further, due to advanced R&D activities and funding, the need for cell culture products, including microcarrier products, is anticipated to grow over the subsequent years. This will provide a significant stimulus to the global market for microcarriers. As per this research report, Global Microcarrier Market was US$ 1.48 Billion in 2021.

Consumables Segment Is Expected to Gain Traction by Grappling Market:

Story continues

By Product, the global microcarrier market is segmented into equipment and consumables. The consumables segment is expected to gain market share by grappling the market through 2021, and the trend is likely to persist during the forecast period. As per our analysis, the blossoming of this segment can be attributed to the rising adoption of microcarrier beads, media, and reagents for various applications, including cell culture procedures.

A Surge in Usage in Research Institutes as End-Users:

Over the past decades, microcarriers of a broad range with various physicochemical properties have been utilized and commercialized amongst end-users. As per our analysis, Pharmaceutical and Biotechnology Companies, Research Institutes, and CROs are the major end-user segments of the microcarriers market. As per our analysis, microcarriers are utilized in various research institutes to help manage patient health. Innovation, discovery, and development in the microcarriers segment, which are helping in making patient management more efficient, are creating a demand for microcarriers.

By Application, Cell and Gene Therapy Show Fastest Growth over the Forecast Period:

Microcarriers are helping in cost-effective cell and gene therapy, i.e., they reduce fixed and variable costs during large-scale manufacturing. The current scenario has changed with technological advancements, and the significance of microcarriers in cell therapy has increased. Along with the statements mentioned above, another factor liable for the expansion of cell therapy applications of microcarriers is that companies are presently focusing on the requirement of microcarriers that donate to large-scale and cost-effective production.

North America is Envisioned to Dominate the Market Over the Forecast Period:

As per our analysis, the North American region is believed to have the largest share in the microcarrier market. The rising gene and cell therapy analysis in the area and the associations sponsoring this research are the major factors supporting its growth. For instance, the American Society of Gene and Cell Therapy are liable for funding the research; this society is compelling the biopharmaceutical and biotech companies to improve their R&D. Besides, the United States is also glimpsing high and rapid augmentation in the biologics and biosimilar Industry. It is one of the influential factors propelling the microcarrier market in the North American region.

Competitive Landscape:

The Microcarrier market is primarily inclusive of the global players, and few companies that are currently dominating the market. The companies working in the sector are Thermo Fisher Scientific, Merck KGaA, Eppendorf AG, Danaher Corporation, Sartorius AG, Lonza Group, Getinge AB Series B, GE Healthcare, Corning Inc and Becton, Dickinson, and Company.

The competition in the market is anticipated to increase as new companies are also coming up in the market. These companies prioritize diverse stages of organic development, such as brand releases, patents, product approvals, and research and development activities. Acquisitions, alliances, and agreements are all considered inorganic growth strategies in this sector.

Key Topics Covered:

1. Introduction

2. Research & Methodology

3. Executive Summary

4. Market Dynamics4.1 Growth Drivers4.2 Challenges4.3 Opportunities

5. Global Microcarriers Market

6. Market Share - Global Microcarriers Analysis6.1 By Product Type6.2 By Application6.3 By End Use6.4 By Region

7. Product - Global Microcarriers Market7.1 Equipment7.2 Consumables

8. Application - Global Microcarriers Market8.1 Biopharmaceutical Production8.2 Cell and Gene Therapy8.3 Tissue Engineering and Regenerative Medicine8.4 Other Applications

9. End Use - Global Microcarriers Market9.1 Pharmaceutical & Biotechnology Companies9.2 Contract Research Organizations & Contract Manufacturing Organizations9.3 Academic and Research Institutes

10. Region - Global Microcarriers Market10.1 North America10.2 Europe10.3 Asia-Pacific10.4 Rest of World

11. Merger and Acquisitions

12. Value Chain Analysis

13. Porters Five Forces

14. Key Players14.1 Thermo Fisher Scientific14.1.1 Overview14.1.2 Recent Development14.1.3 Revenue14.2 Merck KGaA14.2.1 Overview14.2.2 Recent Development14.2.3 Revenue14.3 Eppendorf AG14.3.1 Overview14.3.2 Recent Development14.3.3 Revenue14.4 Danaher Corporation14.4.1 Overview14.4.2 Recent Development14.4.3 Revenue14.5 Sartorius AG14.5.1 Overview14.5.2 Recent Development14.5.3 Revenue14.6 Lonza Group14.6.1 Overview14.6.2 Recent Development14.6.3 Revenue14.7 Getinge AB Series B14.7.1 Overview14.7.2 Recent Development14.7.3 Revenue14.8 GE Healthcare14.8.1 Overview14.8.2 Recent Development14.8.3 Revenue14.9 Corning Inc14.9.1 Overview14.9.2 Recent Development14.9.3 Revenue14.10 Becton, Dickinson and Company14.10.1 Overview14.10.2 Recent Development14.10.3 Revenue

For more information about this report visit https://www.researchandmarkets.com/r/g5q6nl

Attachment

Follow this link:
$2+ Billion Worldwide Microcarrier Industry to 2027 - Rising Demand for Monoclonal Antibodies for Targeted Treatment of Cancer is Expected to Create...

The treatment landscape continues to expand across nonsmall cell lung cancer (NSCLC), with the FDA approvals of multiple agents, including targeted therapies such as sotorasib (Lumakras) and lorlatinib (Lorbrena), according to faculty from an OncLive State of the Science Summit on lung cancer.

The event, chaired by Christine Bestvina, MD, assistant professor of medicine, hematology and oncology (cancer), University of Chicago Medicine Comprehensive Cancer Center, highlighted updates across the lung cancer landscape, including the use of frontline immunotherapy in NSCLC, plus the role CTLA-4 inhibitors could play in this patient population.

Bestvina was joined by her colleagues:

Below, Fidler, Weinberg, Bestvina, Feldman, and Vokes summarize the main messages from their presentations.

Fidler: Comprehensive next-generation sequencing [NGS] is essential for [patients with] stage IV adenocarcinoma. [NGS] should include RNA sequencing and circulating tumor DNA [ctDNA] assays, [which] can maximally capture targeted alterations. We saw that with a [2018 report by Charu Aggarwal, MD, MPH, of Penn Medicine,] where some of the alterations were only captured in the ctDNA assays.

Perioperative PD-L1 [testing] could be useful to guide multimodality therapy, and EGFR testing should be performed on resectable patients that may pursue a neoadjuvant chemotherapy [plus] immunotherapy approach, given the overwhelming disease-free survival benefit with osimertinib [Tagrisso] for [patients with EGFR mutations].

Weinberg: Sotorasib received [FDA] approval in May 2021 for patients with KRAS G12C[mutated] metastatic NSCLC in the second-line setting or later. Adagrasib is a KRAS G12C inhibitor, but it is not yet approved.

In general, [KRAS G12C inhibitors] are tolerated well. Gastrointestinal [adverse] effects [AEs] and liver abnormalities are the largest treatment-related AEs. There is emerging data in studies that we should keep an eye on in terms of combination treatment thats ongoing.

Lorlatinib was approved in March 2021 for the treatment of patients with ALK fusionpositive metastatic NSCLC. Alectinib [Alecensa], for most [clinicians], is still our go-to first-line [treatment] for patients with ALK fusionpositive metastatic NSCLC. But I would consider lorlatinib in the first line if the patient has significant central nervous system metastasis. [It is important to] be aware of the unique [AE] profile of lorlatinib.

Selpercatinib [Retevmo] was FDA approved in May 2020 [for the treatment of patients with RET alterationpositive NSCLC]. Pralsetinib [Gavreto] was approved in September 2020 for the first-line treatment of patients with metastatic NSCLC with RET fusions. [Notably], selpercatinib has less myelosuppressive [AEs].

Larotrectinib [Vitrakvi] was approved in November 2018 [for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment]. Entrectinib [Rozlytrek] was approved in August 2019 for the first-line treatment of solid tumors harboring NTRK fusions without resistance mutations. [Additionally], there are emerging second-generation inhibitors to overcome on-target resistance.

Bestvina: Immune monotherapy is whats preferred for patients [with NSCLC] who have high PD-L1 [expression], although chemotherapy [plus] immunotherapy may be preferred in never smokers or patient [who present with more aggressive disease]. Chemotherapy [plus] immunotherapy is whats recommended to for [patients with] a [PD-L1 tumor proportion score of] less than 50%.

The addition of a CTLA-4 [inhibitor] may be helpful for certain patient subgroups. But stay tuned, because lots of combination trials [are expected] to read out soon.

Feldman: In the paradigm of treatment for extensive-stage SCLC, we want to consider clinical trials. In the first-line setting, [treatment options include] etoposide [and] platinum [chemotherapy combined with] either atezolizumab [Tecentriq] or durvalumab [Imfinzi]. In the second-line setting, we have an FDA approval for topotecan and lurbinectedin [Zepzelca]. Many investigators prefer [liposomal] irinotecan instead of topotecan, although that is an off-label usage.

In the third-line setting for patients who havent had a checkpoint inhibitor, one can consider pembrolizumab [Keytruda] or nivolumab [Opdivo]. Otherwise, we still have agents such as paclitaxel and temozolomide [Temodar] to consider in the third-line setting.

Vokes: Survival [rates] in resectable lung cancer are still too low. Although we should be happy with the [current] results, we shouldnt be content and say we dont have to look any further. Targeted therapies and immune checkpoint inhibitors have significantly improved treatment outcomes, and resection is the key. [Treatment can be given before or after surgery], but the key is to cut [the disease] out, [if possible].

[The use of] adjuvant and neoadjuvant chemotherapies are evidence based. Osimertinib is [FDA] approved [as an adjuvant treatment following tumor resection in EGFR-mutated NSCLC], and atezolizumab [is approved for use as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA NSCLC with a PD-L1 expression on 1% or moreof tumor cells]. Moreover, neoadjuvant nivolumab and [platinum-doublet chemotherapy was recently approved for adult patients with resectable NSCLC].

Continued here:
Targeted Therapies Continue to Expand the Treatment Paradigm in NSCLC - OncLive

- AUTO4: oral presentation on initial clinical experience in peripheral T cell lymphoma- AUTO1/22: oral presentation on initial experience in r/r pediatric B-cell acute lymphoblastic leukemia- obe-cel: poster presentation in r/r primary CNS lymphoma- obe-cel: poster presentation in r/r B-non-Hodgkins lymphoma and chronic lymphoblastic leukemia- Conference call to be held on June 13, 2022 at 7:30 am EST/12:30 pm BST

LONDON, May 12, 2022 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc(Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today announces the online publication of four abstracts submitted to the European Hematology Association (EHA) Congress to be held June 9-12, 2022. Autolus plans to present more detail on these programs and the next steps in a conference call following the EHA presentations, on June 13, 2022, details below.

We are delighted to be presenting encouraging early clinical data from four of our pipeline programs, including important additive safety and efficacy data from our lead asset obe-cel in indications beyond adult r/r B-ALL. These data demonstrate the inherent value in both our pipeline and our technology base from which it originates, said Dr. Christian Itin, Chief Executive Officer of Autolus. With oral presentations on the early safety, tolerability, feasibility and preliminary efficacy of AUTO4 and AUTO1/22, were in a great place to evaluate the next strategic steps for these candidates and further build on the data presented here.

Abstracts to be presented:

Conference Call

Management will host a conference call and webcast on June 13, 2022 at7:30 am ET/12:30 pm BST to discuss the EHA data. To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus website.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID: 6594553. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID: 6594553.

About Autolus Therapeutics plcAutolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the Company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information, please visit http://www.autolus.com.

About obe-cel(AUTO1)Obe-cel is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies.Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, obe-cel may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the ability of the programmed T cells to engage in serial killing of target cancer cells. In collaboration with Autolus academic partner, UCL, obe-cel is currently being evaluated in a Phase 1 clinical trials for B-NHL. Autolus has progressed obe-cel to the FELIX trial, a potential pivotal trial for adult ALL.

About obe-cel FELIX clinical trialAutolus Phase 1b/2 clinical trial of obe-cel is enrolling adult patients with relapsed / refractory B-precursor ALL. The trial had a Phase 1b component prior to proceeding to the single arm, Phase 2 clinical trial. The primary endpoint is overall response rate, and the secondary endpoints include duration of response, MRD negative CR rate and safety. The trial is designed to enroll approximately 100 patients across 30 of the leading academic and non-academic centers in the United States,United KingdomandEurope. [NCT04404660]

About AUTO1/22AUTO1/22 is a novel dual targeting CAR T cell based therapy candidate based on obe-cel. It is designed to combine the enhanced safety, robust expansion & persistence seen with the fast off rate CD19 CAR from obe-cel with a high sensitivity CD22 CAR to reduce antigen negative relapses. This product candidate is currently in a Phase 1 clinical trial called CARPALL for patients with r/r pediatric ALL. [NCT02443831]

About AUTO4AUTO4 is a programmed T cell product candidate in clinical development for T cell lymphoma, a setting where there are currently no approved programmed T cell therapies. AUTO4 is specifically designed to target TRBC1 derived cancers, which account for approximately 40% of T cell lymphomas, and is a complement to the AUTO5 T cell product candidate, which is in pre-clinical development. AUTO4 has been tested in a Phase 1 clinical trial, LibRA1 for patients with peripheral T cell Lymphoma.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus development of the obe-cel program; the future clinical development, efficacy, safety and therapeutic potential of its product candidates, including progress, expectations as to the reporting of data, conduct and timing and potential future clinical activity and milestones; expectations regarding the initiation, design and reporting of data from clinical trials; expectations regarding regulatory approval process for any product candidates; the collaboration between Autolus and Blackstone; the discovery, development and potential commercialization of potential product candidates including obe-cel using Autolus technology and under the collaboration agreement; the therapeutic potential for Autolus in next generation product developments of obe-cel in B-cell malignancies; the potential and timing to receive milestone payments and pay royalties under the strategic collaboration; and the Companys anticipated cash runway. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in such statements. These risks and uncertainties include, but are not limited to, the risks that Autolus preclinical or clinical programs do not advance or result in approved products on a timely or cost effective basis or at all; the results of early clinical trials are not always being predictive of future results; the cost, timing and results of clinical trials; that many product candidates do not become approved drugs on a timely or cost effective basis or at all; the ability to enroll patients in clinical trials; possible safety and efficacy concerns; and the impact of the ongoing COVID-19 pandemic on Autolus business. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Autolus actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 10, 2022, as well as discussions of potential risks, uncertainties, and other important factors in Autolus' subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Autolus undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Contact:

Olivia Manser+44 (0) 7780 471568o.manser@autolus.com

Julia Wilson+44 (0) 7818 430877j.wilson@autolus.com

Susan A. NoonanS.A. Noonan Communications+1-917-513-5303susan@sanoonan.com

Original post:
Autolus Therapeutics to Present Four Clinical Data Updates at the European Hematology Association Congress - GlobeNewswire

On April 25, Nkarta, a biopharmaceutical company developing off-the-shelf engineered natural killer (NK) cell therapies, announced highly promising results from two Phase I trials. The trials were investigating Nkartas two lead chimeric antigen receptor (CAR) NK cell therapy candidates, NKX101 and NKX019.

In the first trial, NKX101, which is engineered to target the NKG2D ligand on cancer cells, was administered to 21 patients, 17 with relapsed/refractory acute myeloid leukaemia (AML), and four with myelodysplastic syndrome (MDS). Three of the five patients with heavily pretreated AML, who received the three-dose regimen of 1-1.5 billion cells, achieved a complete response (CR), with two of these responses being minimal residual disease negative, a good predictor for a durable response. Neither of the two MDS patients who received this dose level had any response. There were responses in AML patients treated with lower dosing regimens; however, no complete responses were reported. The overall response rate (ORR) for AML patients across dosing levels was 47%.

In the second trial, NKX019, which is engineered to target the B-cell antigen CD19, was administered to ten patients with heavily pretreated non-Hodgkin lymphoma (NHL), and three patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (B-ALL). Three of the six NHL patients who received three doses of 1 billion cells achieved a CR, and the ORR was 83%. The ORR across dosing levels for NHL patients was 70%. No responses were reported in the three patients with B-ALL.

CAR T-cells are the first class of engineered immune cells to have received regulatory approval. CAR T-cell therapies, both marketed and in development for the treatment of haematological malignancies, have demonstrated very impressive response rates. While this class of therapeutics has provided a cure for some patients, significant challenges of utilising CAR T-cells remain. The toxicities associated with CAR T-cell treatment are serious and sometimes fatal, including cytokine release syndrome, graft-versus-host disease (GvHD) and neurotoxicity. The cost associated with CAR T-cell treatment is also significant, with the expansion and engineering of autologous cells required for each patient. The autologous nature of these products also means that it takes several weeks from T-cell collection until the product is ready for infusion, with this delay increasing the risk of disease progression. The drawbacks associated with CAR T-cells have driven the development of CAR NK-cells, with no dose-limiting toxicities reported for either NKX101 or NKX019. No cases of cytokine release syndrome, neurotoxicity or GvHD occurred in either trial. With no human leukocyte antigen (HLA)-matching restrictions, CAR-NK therapies can be off-the-shelf products, reducing the cost of therapy and enabling rapid treatment initiation.

The findings reported by Nkarta demonstrate the potential of this novel therapy class. However, it remains to be seen whether the responses are durable and provide curative treatment, as has been observed with CAR T-cell therapies. Nkarta will face competition from other biotech companies developing CAR-NK cells, including Fate Therapeutics, Affimed and Asclepius Technology. Breakthroughs in the development of allogeneic CAR T-cells mean that off-the-shelf CAR T therapies with reduced toxicity may also enter this treatment landscape.

Pharmaceutical Translations from English into Balkan Languages

The development of cell therapies is changing healthcare, delivering new hope to thousands of patients around the world. The vein-to-vein workflow for these therapies, however, is not without challenges, many of which will increase as we scale up to treat more patients. Download this free guide from Cytiva to learn more about the challenges and risks associated with the cryogenic supply chain for cell therapies, and how supply chain disruptions can best be mitigated.

By clicking the Download Free Whitepaper button, you accept the terms and conditions and acknowledge that your data will be used as described in the Cytiva Thematic privacy policy

By downloading this Whitepaper, you acknowledge that we may share your information with our white paper partners/sponsors who may contact you directly with information on their products and services.

Visit our privacy policy for more information about our services, how we may use, process and share your personal data, including information on your rights in respect of your personal data and how you can unsubscribe from future marketing communications. Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address.

More:
Complete responses reported for Nkarta's off-the-shelf NK cell therapies - Clinical Trials Arena

Investigators observed low enrollment of Black patients on CAR T-cell therapy clinical trials that supported FDA decisions in hematologic malignancies, especially in multiple myeloma.

Enrollment on CAR T-cell clinical trials supporting FDA approvals was notably low among Black patients with hematologic cancers, especially those with multiple myeloma, according to a findings from a study presented at the 2022 Tandem Meeting.

Investigators noted that efficacy data were reported for 74% of the 1051 patients who enrolled on a clinical trial and received treatment with a CAR T-cell therapy. Of the 782 patients who were treated in the trials, only 28 (3.6%) were Black.

As the participation of Black patients in clinical trials that support CAR T-cell therapies has not been well described, investigators launched an analysis to assess and identify any relevant disparities. FDA approvals examined in the analysis took place from August 3, 2017, to March 26, 2021. Almost all patients (96%) who enrolled resided within the United States.

The analysis included 7 clinical trials that led to the approval of several CAR T-cell therapies across different indications:

Investigators calculated the prevalence-corrected estimates for enrollment of Black patients by dividing the percentage of Black patients within a clinical trial population by the percent of Black patients in the disease population.

The most common disease types represented include diffuse large B-cell lymphoma (DLBCL; 58%) and multiple myeloma (16%). Of the 7 studies included in the analysis, 2 did not report racial or ethnic information. Of the overall trial populations, 4% of patients with DLBCL, 6% of patients with multiple myeloma, and 1% of patients in other indications were Black. After adjusting for disease prevalence, investigators reported that participation to prevalence ratio was 0.2 for multiple myeloma, 0.4 for mantle cell lymphoma, 0.6 for DLBCL, and 0.8 in follicular lymphoma.

Al Hadid S, Schinke C, Thanendrarajan S, et al. Enrollment of Black Americans in pivotal clinical trials supporting Food and Drug Administration (FDA) chimeric antigen receptor (CAR)-T cell therapy approval in hematological malignancies. Presented at: 2022 Tandem Meeting; April 23-26, 2022; Salt Lake City, UT. Abstract 248.

Original post:
Enrollment Low for Black Patients With Hematologic Malignancies On Trials Supporting FDA Approvals of CAR T-Cell Therapy - Cancer Network

Docket Number: FDA-2009-D-0132-0016 Issued by:

Guidance Issuing Office

Center for Biologics Evaluation and Research

Since the issuance of the "Points to Consider (PTC) in Human Somatic Cell Therapy and Gene Therapy"in 1991, the range of gene therapy proposals has expanded to include additional classes of vectors and use of vectors in vivo via direct vector administration to patients. This guidance document updates and replaces the 1991 PTC with new information intended to provide manufacturers with current information regarding regulatory concerns for production, quality control testing, and administration of recombinant vectors for gene therapy; and of preclinical testing of both cellular therapies and vectors. These guidances are not regulations, but rather represent issues that the Center for Biologics Evaluation and Research (CBER) staff believes should be considered at this time.

You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))

If unable to submit comments online, please mail written comments to:

Dockets ManagementFood and Drug Administration5630 Fishers Lane, Rm 1061Rockville, MD 20852

All written comments should be identified with this document's docket number: FDA-2009-D-0132-0016.

04/21/2021

Read more here:
Guidance for Human Somatic Cell Therapy and Gene Therapy | FDA

DUBLIN, April 25, 2022--(BUSINESS WIRE)--The "Adoptive Cell Therapy Market, by Type, By Application, by End User, and by Region - Size, Share, Outlook, and Opportunity Analysis, 2022 - 2030" report has been added to ResearchAndMarkets.com's offering.

Adoptive cell therapy (ACT) is a type of immunotherapy in which T cells (a type of immune cell) are given to a patient to help the body fight diseases, such as cancer. Types of adoptive cell therapy include chimeric antigen receptor (CAR) T cells, T cell receptor (TCR) T cells, tumor infiltrating lymphocytes (TILs), and natural killer (NK) cells.

Adoptive cell therapy involve use of immune cells that are grown in the lab in large numbers followed by administering them to the body to fight cancer. Sometimes, immune cells that naturally recognize melanoma are used, while other times they are modified to make them recognize and kill the melanoma cells. Adoptive cell therapy is also called T-cell transfer therapy, and cellular immunotherapy.

Key players operating in the global adoptive cell therapy market are focusing on adoption of growth strategies such as product launch, collaboration, and fundraise which are expected to drive the market growth during the forecast period.

Key features of the study:

This report provides an in-depth analysis of the global adoptive cell therapy market, and provides market size (US$ Mn) and compound annual growth rate (CAGR%) for the forecast period (2022-2030), considering 2021 as the base year

It elucidates potential revenue opportunities across different segments and explains attractive investment proposition matrices for this market

This study also provides key insights about market drivers, restraints, opportunities, new product launches or approval, market trends, regional outlook, and competitive strategies adopted by key players

It profiles key players in the global adoptive cell therapy market based on the following parameters - Company Highlights, Products Portfolio, Key Highlights, Financial Performance, Strategies

Insights from this report would allow marketers and the management authorities of the companies to make informed decisions regarding their future product launches, type up-gradation, market expansion, and marketing tactics

The global adoptive cell therapy market report caters to various stakeholders in this industry including investors, suppliers, product manufacturers, distributors, new entrants, and financial analysts

Stakeholders would have ease in decision-making through various strategy matrices used in analyzing the global adoptive cell therapy market

Story continues

Market Segmentation:

Global Adoptive Cell Therapy Market, By Type:

Global Adoptive Cell Therapy Market, By Application:

Global Adoptive Cell Therapy Market, By End User:

Hospitals

Cancer Treatment Centers

Global Adoptive Cell Therapy Market, By Region:

North America

U.S.

Canada

Latin America

Brazil

Mexico

Argentina

Rest of Latin America

Europe

Germany

U.K.

France

Italy

Spain

Russia

Rest of Europe

Asia Pacific

China

India

Japan

Australia

South Korea

ASEAN

Rest of Asia Pacific

Middle East

GCC

Israel

Rest of Middle East

Africa

South Africa

Central Africa

North Africa

Company Profiles

Novartis AG.

Gilead Sciences, Inc.

Castle Creek Biosciences, Inc

Lineage Cell Therapeutics, Inc.

Transgene SA

Cellectis

ImmunityBio, Inc

Sorrento Therapeutics

bluebird bio, Inc.

Arcellx

Sana Biotechnology, Inc.

Biodesix, Inc

Laurus Labs

For more information about this report visit https://www.researchandmarkets.com/r/kffwgd

View source version on businesswire.com: https://www.businesswire.com/news/home/20220425005562/en/

Contacts

ResearchAndMarkets.comLaura Wood, Senior Press Managerpress@researchandmarkets.com For E.S.T Office Hours Call 1-917-300-0470For U.S./CAN Toll Free Call 1-800-526-8630For GMT Office Hours Call +353-1-416-8900

Read the original here:
Worldwide Adoptive Cell Therapy Industry to 2030 - Featuring Novartis, Gilead Sciences and Cellectis Among Others - ResearchAndMarkets.com - Yahoo...