Taiga Nishihori, MD, senior member in the Blood & Marrow Transplant and Cellular Immunotherapy Department at Moffitt Cancer Center, discusses a study in which investigators evaluated patients with relapsed and/or refractory (R/R) multiple myeloma who were hospitalized and treated with commercial ciltacabtagene autoleucel (cilta-cel; Carvykti) at Moffitt Cancer Center between May 2022 and May 2023.

Patients in the initial group to be evaluated were given lymphodepleting chemotherapy as outpatient, followed by chimeric antigen receptor (CAR) T-cell infusion as inpatient. Patients were also monitored, then discharged to an outpatient immune cell therapy service. The first 30 days post-infusion was the focus of the study.

Transcription:

0:09 | We wanted to look at our experience on treating patients with multiple myeloma who received cilta-cel, which is a CAR T-cell [therapy]. We started looking at this in 2022. Initially, we started doing an outpatient model, which was the beginning of it, and then we changed it to inpatient. The chemotherapy was given, lymphodepletion in particular, and chemotherapy was given as an outpatient; they readmitted patients. But then, we quickly realized that patients who are in the hospital were basically spending a lot of time waiting for toxicity to occur. We changed our approach entirely outpatient. And then we looked at over 20 patients who received those. We also demonstrated that the amount of time they spend in a hospital has been cut down from 11 days to a median of 4 days.

1:11 | We wanted to look at the hospital duration. We also wanted to look at the outcomes of this approach. We have established our system to take care of patients, mostly on the outpatient side. The patients are seen daily in what is called 3 central outpatient areas, and we have managed to conduct this safely as an outpatient.

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Study Focuses on Outpatient CAR T-Cell Therapy in Multiple Myeloma - Targeted Oncology

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Designing drug delivery systems for cell therapy - Nature.com

Once a month, Talaya Reid wakes up early to board a flight from Philadelphia to Boston, in hopes of impacting research into lupus and the potential benefits of chimeric antigen receptor (CAR) T cell therapy to treat the chronic autoimmune disease.

Reid travels to UMass Chan Medical School in Worcester to participate in an individualized clinical research study exploring the use of CAR T cell treatment in lupus nephritis for severe or nonresponsive lupus. The Lupus Center at UMass Chan is one of five national sites participating in the trial sponsored by Kyverna Therapeutics. Reid is one of a dozen patients in the United States to have undergone CAR T cell treatment for lupus.

Ive participated in treatments before that have calmed my lupus symptoms down, but the symptoms were still there, or the treatments did nothing at all. When I heard it was possible to live without lupus symptoms or flare ups anymore, I was very interested in participating in this trial, Reid said.

Roberto Caricchio, MD, theMyles J. McDonough Chair in Rheumatology, professor of medicine, chief of the Division of Rheumatology in the Department of Medicine and director of the Lupus Center at UMass Chan, is principal investigator of the CAR T cell therapy trial in lupus at UMass Chan.

This treatment is not for everyone. It is for those patients who unfortunately have gone through several treatments that we have available and somehow the lupus does not seem to be matched by them. Its a significant, but restricted group of patients. And within that group of patients, it takes a special individual who is looking for something different and commits to something new, Dr. Caricchio said.

Lupus is a chronic autoimmune disease that involves multiple organ systems and often requires lifelong treatment with immunosuppressive or immunomodulatory drugs, which are not effective for all patients. Lupus nephritis is a complication of lupus that causes inflammation of the kidneys, impacting the bodys ability to remove waste from the blood or regulate body fluids.

"Ive participated in treatments before that have calmed my lupus symptoms down, but the symptoms were still there, or the treatments did nothing at all. When I heard it was possible to live without lupus symptoms or flare ups anymore, I was very interested in participating in this trial."

CAR T cell therapy has been recognized as a significant advancement in treating cancers such as leukemia, lymphoma and more recently, multiple myeloma. CAR T cells are created by removing some of a patients white blood cells, including immune system T cells, and genetically altering them in a lab to produce CARs. These changes help the patient's T cells identify and kill antigens on the outside of the harmful cells once they are put back into the body.

Reids first treatment in March required a two-week hospital stay, during which she underwent lymphodepletion chemotherapy and an infusion of her CAR T cells and was monitored by medical personnel in the Blood and Marrow Transplant program at UMass Memorial Medical Center. She stayed in the Worcester area for three weeks after her discharge from the hospital before transitioning to monthly visits.

Each monthly visit to the Lupus Center at UMass Chan requires an assessment by a trained provider and extensive bloodwork at UMass Memorial Medical Center-Memorial Campus. During her day-long visit, Reid has more than 15 vials of blood taken. The blood samples are separated into two categories: for future Lupus research and for understanding what the CAR T cell therapy treatment is doing for her.

Once her bloodwork is completed, Reid travels back to Boston to catch a plane home to Philadelphia.

If her lupus symptoms havent flared up again, she will only need to come to Worcester for one visit in 2025. She will continue to be observed by the Lupus Center at UMass Chan for at least two years.

As of now, I can say that this is the best I've ever felt. I feel really good, said Reid, 28, a pharmaceutical scientist from Fairless Hills, Pennsylvania, who was diagnosed with lupus at 22. She said her flares previously ranged from minimalfatigue or discomfortto major, with joint pain and/or migraines that impacted her ability to attend college classes or work.

According to Caricchio, the Lupus Center has enrolled a second patient in the CAR T cell therapy trial who is expected to begin treatment in July.

This treatment not only helps the patients currently participating in these trials, but also future patients, Caricchio said. It has been a very strong learning experience. The plus is that this type of treatment isnt only groundbreaking but will also teach us a lot about lupus itself as a disease and we will be able to capitalize on that and find better ways to help patients.

Caricchio cautioned that all results are preliminary, saying, It is important to remember that this is an experimental treatment and therefore only upon completion of the clinical trial will we know if this approach is truly transformative for lupus patients.

The Lupus Center is led by Caricchio and Elena Gkrouzman, MD, assistant professor of medicine, and includes a team of dedicated experts, including rheumatologists, dermatologists and nephrologists, as well as clinical research coordinators.

The CAR T cell therapy clinical trial at the Lupus Center at UMass Chan is conducted in collaboration with the Cancer Research Office at the UMass Cancer Center; the Blood Cancer Center physicians and teams, including Jan Cerny, MD, PhD, associate professor of medicine; Muthalagu Ramanathan, MD, professor of medicine; and Poorva Bindal, MD, assistant professor of medicine; and the Divisions of Hematology/Oncology and Renal Medicine/Nephrology.

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Lupus Center at UMass Chan investigating CAR T cell therapy for severe or nonresponsive lupus nephritis - UMass Medical School

FDA Grants Fast Track Designation to ADI-270 for Pretreated Advanced ccRCC

A fast track designation has been granted by the FDA to ADI-270 as a potential therapy option for patients with metastatic or advanced clear cell renal cell carcinoma (ccRCC) previously treated with an immune checkpoint inhibitor and a VEGF inhibitor.1

ADI-270 is an allogeneic, off-the-shelf, CD70-targeted gamma delta CAR T-cell therapy candidate. It is directed toward CD70 using the natural CD27 receptor and features a dominant negative form of the transforming growth factor- receptor II intended to deliver functional resilience to the immunosuppressive tumor microenvironment. Furthermore, ADI-270 is intended to increase exposure and persistence by reducing susceptibility to graft-vs-host elimination.

We are pleased that ADI-270, our first ever gamma delta 1 CAR T-cell therapy candidate to enter clinical trials for solid tumors, has been granted fast track designation by the FDA, Chen Schor, president and chief executive officer of Adicet Bio, stated in a news release. ccRCC is the most common type of kidney cancer, and this significant milestone underscores our commitment to advancing innovative treatments to these patients as quickly as possible.

Findings from preclinical studies presented at the 2023 American Society of Gene + Cell Therapy Annual Meeting showed that ADI-270 successfully generated and expanded without indications of fratricide. The agent also displayed a less-differentiated T-cell memory phenotype with low expression of exhaustion markers; potent in vitro cytotoxicity; and favorable cytokine and chemokine profiles.2

Additionally, ADI-270 generated highly potent tumor growth inhibition via xenografts in immunodeficient mice. Furthermore, selective T-cell infiltration, proliferation, and activation were observed within the tumor.

A phase 1/2 trial (NCT06480565) will investigate ADI-270 in patients at least 18 years of age with histologically or cytologically confirmed ccRCC who have documented evidence of advanced or metastatic disease. Prior treatment with an immune checkpoint inhibitor and a VEGF inhibitor is required; notably, the VEGF inhibitor must have been given in the advanced/metastatic setting. Other key inclusion criteria include at least 1 measurable target lesion per RECIST v1.1 criteria and a Karnofsky performance status of at least 70. Patients will need to be at least 3 weeks or 5 half-lives removed from their last dose of prior therapy.3

The study will exclude patients with central nervous system (CNS) metastases or spinal cord compression, unless they have finished treatment and discontinued corticosteroids for at least 8 weeks and remain stable prior to enrollment. Other key exclusion criteria include clinically significant CNS dysfunction; prior radiation therapy within 21 days prior to start of study treatment, except for palliative radiotherapy to bone lesions completed at least 2 weeks prior to the first study treatment; prior gene therapy, genetically modified cell therapy, or adoptive T-cell therapy within 6 weeks of enrollment; and any prior treatment with a CD70-targeted therapy.

The trial will also exclude patients with an active malignancy within the past 24 months, other than RCC; definitively treated basal or squamous cell carcinoma of the skin; or carcinoma in-situ of the cervix or bladder. Patients with any primary immunodeficiency or active autoimmune disease requiring ongoing systemic immunosuppressive therapy will also be excluded.

Enrolled patients will undergo lymphodepletion with fludarabine plus cyclophosphamide prior to receiving a single dose of ADI-270. During dose escalation, ADI-270 will be given at ascending dose levels to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD). Dose expansion will further evaluate the CAR T-cell therapy at the MTD/MAD.

The primary end points of the study are the incidence of dose-limiting toxicities and the proportion of treatment-emergent and -related adverse effects.

References

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FDA Grants Fast Track Designation to ADI-270 for Pretreated Advanced ccRCC - http://www.oncnursingnews.com/

Pluris newly launched CMDO business will manufacture two novel cell therapy product candidates for Kadimastem.

On July 18, 2024, Israel-based biotechnology company, Pluri, announced that it has signed a tech transfer and manufacturing agreement with Kadimastem, an Israel-based clinical stage biotechnology company developing therapeutic cells to treat amyotrophic lateral sclerosis (ALS) and diabetes. Under the agreement, PluriCDMO, Pluris contract development and manufacturing organization (CDMO) business launched in January 2024 (1), will manufacture two cell therapy product candidates for Kadimastem at its 47,000-ft2 good manufacturing practice (GMP) cell production facility at its MATAM Advanced Technology Park site in Haifa, Israel (2).

The two cell therapy product candidates from Kadimastem are AstroRx, clinical-grade human astrocytes (nervous system supporting cells) for the treatment of ALS, and IsletRx, clinical-grade pancreatic islet cells that produce and secrete insulin and glucagon in response to blood glucose levels. The material PluriCDMO produces for AstroRx will supply an upcoming FDA Phase II study. Meanwhile, IsletRx is in development for treating diabetes.

Working with Pluri marks a pivotal milestone, enhancing Kadimastems capacity to manufacture our products under GMP conditions, said Ronen Twito, executive chairman and president of Kadimastem, in a company press release. This collaboration is integral to our strategy as we prepare for clinical trials and expand into the US market with our AstroRx product candidate.

Kadimastems decision in selecting PluriCDMO is based on Pluris expertise and experience in developing and manufacturing GMP-grade cell-based products for clinical use. The CDMO has the capacity to scale up from initial clinical trial batches to mass-scale commercial production, according to Pluri in the press release.

Pluris CDMO division offers access to its patented bioreactor system, which enables 3D cell expansion at mass scale using a fully controlled, automated, and validated process. The companys 3D cell expansion technology supports the large-scale growth of cells and offers unique batch-to-batch consistency in a scalable, cost-effective manner that can support late-stage clinical trials in key jurisdictions, including FDA, the European Medicines Agency, Israelis Ministry of Health, Japans Pharmaceuticals and Medical Devices Agency, and the Ministry of Food and Drug Safety of the Republic of Korea. In addition, the companys PluriMatrix technology enables industrial-scale production of cell-based products (1).

We are excited to work with Kadimastem and support their development of cell therapies, potentially improving the lives of patients with ALS and diabetes, said Yaky Yanay, chief executive officer and president of Pluri, in the press release. This collaboration underscores the versatility of our PluriCDMO platform and our commitment to aiding innovative companies in advancing their life-saving therapies. We look forward to a successful collaboration with Kadimastem as they make progress with their clinical development programs.

Kadimastem specializes in developing allogeneic (i.e., off-the-shelf) proprietary cell products based on its technology platform, which enables the expansion and differentiation of human embryonic stem cells (hESCs) into functional cells.

1. Pluri. Pluri Launches Advanced Global Cell Therapy Contract Development and Manufacturing Organization. Press Release, Jan. 8, 2024. 2. Pluri. 10KAnnual 2023 Financial Report. http://www.sec.gov. Sept. 12, 2023.

Source: Pluri

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Pluris CDMO Business to Manufacture Cell Therapy Candidates from Kadimastem - BioPharm International

Six months after winning fast track status for multiple sclerosis, Kyverna Therapeutics KYV-101 has secured another US Food and Drug Administration (FDA) designation; this time, a regenerative medicine advanced therapy (RMAT) tag for the treatment of stiff-person syndrome.

An RMAT designation includes those benefits included in the fast track and breakthrough therapy pathways such as a priority review, along with early and enhanced FDA interactions. The RMAT tag also permits the use of surrogate endpoints in clinical trials studying the therapy, which can lead to accelerated approval.

Shares in the US biotech rose 9.5% at market open compared to a pre-announcement 15 July market close. Kyverna has a market cap of $427m.

Kyvernas KYV-101 is a CD19 chimeric antigen receptor (CAR)-T cell therapy designed for B cell-driven autoimmune disorders. It is currently being evaluated in a Phase II trial in patients with treatment-refractory stiff-person syndrome. The study, named KYSA-8, received the FDA greenlight last month.

The RMAT applications success was based on the positive clinical outcomes of KYV-101 in patients treated in Germany under a named patient treatment option, according to a 16 July press release.

Kyverna has not revealed further information about the US trial, with the biotechs CEO Peter Maag saying we are eager to begin generating data.

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Stiff-person syndrome is a progressive autoimmune disorder that causes muscle stiffness and spasms in the torso and limbs. Many patients can break bones from falling as they lack the necessary muscle reflexes for correction. It is not known what causes the disease.

Kyverna is considering cell therapy treatments beyond blood cancers, the space in which many CAR-T treatments are currently approved to treat. KVY-101 is being evaluated in sponsored Phase I/II and Phase II trials in the US and Germany in indications such as refractory lupus nephritis (NCT05938725), multiple sclerosis, and myasthenia gravis. The biotech reported positive Phase I results for the cell therapy in multiple sclerosis patients in April this year, the indication for which the drug has fast track status from the FDA.

In total, Kyverna says that 50 patients with cancer or autoimmune conditions have been treated with KYV-101 so far.

Kyverna went public earlier this year, raising $319m in the process. The initial public offering (IPO), which was larger than expected, saw the company sell 14.5 million shares for $22 each.

Cell & Gene Therapy coverage on Pharmaceutical Technology is supported byCytiva.

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Kyverna wins RMAT designation for stiff-person syndrome for cell therapy candidate - Pharmaceutical Technology

Francisco Hernandez-Ilizaliturri, MD

As bispecific antibodies gain traction in the diffuse large B-cell lymphoma (DLBCL) treatment paradigm, patient characteristics such as frailty, fitness, and disease risk influence how Francisco Hernandez-Ilizaliturri, MD, selects and sequences treatment with bispecific antibodies and CAR T-cell therapies.

Version 2.2024 of the NCCN Clinical Practice Guidelines in Oncology for B-Cell Lymphomas, which were released in April 2024, include axicabtagene ciloleucel (Yescarta) and lisocabtagene maraleucel (Breyanzi) as recommended second-line therapies, and bispecific antibodies, such as epcoritamab-bysp (Epkinly), are recommended in the third- and subsequent-line settings.1

Bispecific antibodies are another form of T-cell engager therapy, and their activity has been proven in clinical trials not only in relapsed/refractory large-cell lymphoma, but also in follicular lymphoma, [and] to a lesser degree in other types of lymphomas, Hernandez-Ilizaliturri said in an interview with OncLive. Some of them are approved for patients with relapsed/refractory large-cell lymphoma, so in this context we are trying to weigh the choice of CAR T-cell therapy [vs a] bispecific antibody.

In the interview, Hernandez-Ilizaliturri detailed how he selects and sequences treatments for patients with DLBCL, and also provided insights into the multiple myeloma space regarding how the FDA approvals of the CAR T-cell therapies ciltacabtagene autoleucel (cilta-cel, Carvykti) and idecabtagene vicleucel (ide-cel, Abecma) have provided more options for patients in earlier lines of treatment. Hernandez-Ilizaliturri is the director of Lymphoma Research, head of the Lymphoma Translational Research Laboratory, a professor of oncology, and an associate professor in the Department of Immunology at Roswell Park Comprehensive Cancer Center in Buffalo, New York.

Hernandez-Ilizaliturri: The approval of CAR T-cell therapy in multiple myeloma highlights the principle that these novel forms of immunotherapy can be applied to cancers beyond B-cell lymphomas. They provide therapeutic strategies for patients who are youngwhen they have good kidney function[and] need to have disease control.

The activity [observed] in the 2 clinical trials with each of the CAR T-cell therapy products also highlights the need to develop new treatments because in contrast with what we see with B-cell lymphoma, the duration of the activity is not as long. Sometimes we should not wait too long to implement these treatments because the more damaged the immune system is in a patient from prior treatments, the less likely it is that these kinds of immunotherapies are going to [be effective] for a long time.

[The data] also stressed the need to learn how those myeloma cells may be further affecting CAR T-cell function, so we can develop a better way to apply this technology to have better clinical activity. [These are] encouraging data that are going to change the way that we practice, but it opens a lot of questions and is forcing industry to partner with academic centers to develop better CAR T-cell products for myeloma.

In general, we have longer follow-[up] data with CAR T-cell therapy; we can be comfortable assuming that CAR T-cell therapy can cure [approximately] 30% to 40% of patients with relapsed or refractory LBCL. Whereas the follow-up of patients treated with bispecific antibodies is not long enough to see if patients are being cured with this intervention. For a patient who is younger and fit, it may be better to start with a CAR T-cell therapy product because there is longer follow-up data and we have become more proficient in treating acute toxicitiesthat mitigates some of the concerns about that treatment.

If a patient is frailer, a bispecific antibody may be more suitable. [Treatment selection] also has to do with the geographic location of the patient and their access to CAR T-cell therapy. One of the benefits of bispecific antibodies is that they can be administered close to the patients home, as long as the physician is comfortable using the bispecific antibody and monitoring the adverse effects.

Its encouraging that bispecific antibodies have shown activity in patients previously treated with CAR T-cell therapy. A way to sequence these treatments would be to first start with CAR T-cell therapy and then [administer] a bispecific antibody in patients with high-grade lymphoma. This may change, as there are some interesting emerging data [regarding] combining bispecific antibodies with rituximab [Rituxan] or CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] in patients with high-risk DLBCL or large cell lymphoma.

There are data looking at combining the bispecific antibody [epcoritamab] with R-CHOP [rituximab plus CHOP] and the ORR [was] 100% [in 31 patients with high-risk DLBCL treated in the phase 1/2 EPCORE NHL-2 (NCT04663347) trial]. There are ongoing randomized trials in the first-line setting combining a bispecific antibody with R-CHOP vs R-CHOP in DLBCL [as well].

We dont know if bispecific antibodies will move into the first-line setting at [some] point, but in the relapsed/refractory setting the most logical treatment sequence will be to do CAR T-cell therapy followed by a bispecific antibody; that thought process may be different in follicular lymphoma because patients tend to be elderly, have medical problems, and, in general, the disease is not pacing too aggressively. [Therefore], patients may be more suited to receive a bispecific antibody first and followed by CAR T-cell therapy, but this is a moving field. We have to be open-minded [with] the capacity of these 2 technologies to see how were going to learn to sequence them better in the future.

NCCN. Clinical Practice Guidelines in Oncology. B-Cell Lymphomas, version 2.2024. Accessed July 12, 2024. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf

Link:
Sequencing of Bispecific Antibodies vs CAR T-Cell Therapies is Dependent on Several Factors in DLBCL, Multiple Myeloma - OncLive

Sarcoma is a type of cancer that affects the body's connective tissue, and as such can appear in any part of the body where this type of tissue is found.1 According to the Sarcoma Foundation of America, sarcoma constitutes 15% to 20% of all cancers in children, but is relatively rare in adults, for whom it constitutes 1% of cancers.

In about half of cases, sarcoma is incurable with currently available treatments, including surgery, chemotherapy, and radiation therapy. As such, great unmet need remains for patients with sarcoma.

An important area of interest for new therapeutic development in sarcoma is cell/gene therapy, which a number of companies and academic institutions are now pursuing. In honor of Sarcoma Awareness Month, observed annually in July by the patient and clinician communities, CGTLive is taking a look back at the progress that has been made for cell/gene therapy candidates in sarcoma over the past year. Click the "READ MORE" buttons for more details and information about each item.

June 5, 2024 The IGNYTE-ESO (NCT03967223)substudy 2 evaluating letetresgene autoleucel (lete-cel; Adaptimmune) in patients with synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) met its primary endpoint of safety and efficacy at a planned interim analysis, with a 40% overall response rate in evaluable participants.

Data from the substudy were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31 - June 4, in Chicago, Illinois, by Sandra P. DAngelo, MD, sarcoma oncologist, cellular therapist, and associate attending physician, Memorial Sloan Kettering Cancer Center.

[These data] support the potential of lete-cel as a novel therapy for patients with advanced or metastatic SS and MRCLS. The primary analyses will be presented late 2024 (sic). Further analyses of translational correlates are pending, DAngelo said during her presentation.

May 11, 2024 CCNG1-targeted Deltarex-G gene therapy plus an FDA approved drug (Deltarex-G+) showed some evidence of response in patients tumors, including pancreatic cancer, breast cancer, and sarcoma. All tested tumors had enhanced CCNG1 expression.

Data from the BLESSED expanded access study (NCT04091295) were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, by Erlinda Gordon, MD, founder and president, Aveni Foundation, and director, biological and immunological therapies, and chairman, institutional biosafety committee director, Cancer Center of Southern California/Sarcoma Oncology Center, and founder, chief operating officer, and FDA liaison, Counterpoint Biomedica.

Deltarex-G is the only tumor targeted gene therapy that can be injected intravenously and it in vivo gets into the tumor microenvironment by binding to abnormal signature proteins in the tumor. So, it's unlike the ex vivo gene therapies for cancer... it's an off the shelf gene therapy product that has a navigation system that goes to the tumor itself, Gordon told CGTLive during the meeting. We tested that... CCNG1 is present in all the tumor types that we have tested including sarcoma, pancreatic cancer, breast cancer, testicular cancer, bladder cancer, so that we think it's a tumor agnostic therapy, rather than looking for a very rare oncogene to target."

February 22, 2024 Modified natural killer (NK) cells (IL1RAP CAR NK, TGFi-NK, IL1RAP CAR CXCR2 NK) demonstrated enhanced antitumor activity alone and combined with NKTR-255 and dinutuximab against Ewing Sarcoma (ES) tumor cells in vitro, providing rationale for further preclinical study of these cells.

The preclinical data were presented by Wen Luo, PhD, assistant professor, Pediatrics and Pathology, New York Medical College, at the 2024 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in San Antonio, Texas, February 21-24, 2024.

ES is a malignant pediatric bone associated sarcoma and it is characterized by fusion oncogene in EWS/FLI. Patients with localized ES have around 75% 5-year overall survival (OS) but for patients with metastatic disease, they only have a dismal outcome of around 30% 5-year OS, and patients with relapsed/refractory disease have only 5% 6-month event-free survival. Current treatment including surgery, radiation, and chemotherapy have failed to improve patient outcomes for decades, so novel therapeutics strategies are urgently needed, Luo said during her presentation.

February 2, 2024 Adaptimmune Therapeutics biologics license application for afamitresgene autoleucel (afami-cel, formerly ADP-A2M4), an investigational T-cell receptor (TCR) T-cell therapy intended to treat SS, has been accepted by the FDA with priority review. The Prescription Drug User Fee Act (PDUFA) target action date has been set for August 4, 2024.

The FDAs acceptance of the BLA submission brings us onestep closer to redefining treatment for people with SS, Adrian Rawcliffe, BSc, the chief executive officer of Adaptimmune, said in a statement.Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-celthe first engineered T-cell therapy on the market for a solid tumor cancer.

Afami-cel targets MAGE-A4-expressing solid tumors. It is delivered as a single-dose, and intended to treat patients with advanced SS. The majority of patients who are treated with current standard of care therapy for advanced SS experience disease relapse and in many cases they are left with no further FDA-approved treatment options after receiving multiple lines of therapy.

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Sarcoma Awareness Month 2024: Looking Back at a Year of Progress for Cell and Gene Therapy - CGTLive

The FDA has granted priority review of the biologics license application (BLA) for tabelecleucel (tab-cel) as a monotherapy to treat adult and pediatric patients two years of age and older with Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD). The Prescription Drug User Fee Act (PDUFA) target action date is Jan. 15, 2025.

Lymphoproliferative disease is a rare but life-threatening complication after organ or stem-cell transplants. Many cases are associated with Epstein-Barr virus, accounting for more than 75% of post-transplant lymphoproliferative disease, according to one estimate. Most people have been infected with Epstein-Barr at some point in their lives. The immune suppression used after a transplant can reactivate the virus, causing B cells to grow uncontrollably.

There is no treatment available specifically for Epstein-Barr virus related post-transplant lymphoproliferative disease, but Rituxan (rituximab) and chemotherapy are often used to treat the disease.

Developed by Atara Biotherapeutics, tab-cel is an allogeneic, T-cell immunotherapy designed to target and eliminate cells infected with Epstein-Barr virus. If approved, it would be indicated for those patients who been treated with at least one other therapy.

The FDAs granting of priority review highlights the high unmet need in EBV+ PTLD, which is a devastating disease with limited treatment options and a poor overall survival rate, Pascal Touchon, president and CEO of Atara, said in a news release.

The BLA is supported by data from more than 430 patients treated with tab-cel across multiple life-threatening diseases, including the pivotal ALLELE study that met its primary endpoint. Interim data from this study found that 22 of 43 (51.2%) Epstein-Barr virus related post-transplant lymphoproliferative disease patients achieved an objective response rate (ORR). The median duration of response was 23 months and the median overall survival was 18.4 months.

Tab-cel was well tolerated with no reports of tumor flare reaction, cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, and there were no events of graft-versus-host disease or solid organ transplant rejection related to treatment. These data werepreviously presentedat the 2022 American Society of Hematology (ASH) Annual Meeting.

An updated analysis from the October 2023 data cut off of the ALLELE study continued to demonstrate a statistically significant 49% ORR. These data were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

Tab-cel is approved in Europe with the brand name Ebvallo.

Atara has partnered with Pierre Fabre Laboratories for development, manufacturing, and commercialization rights in Europe and the United States. The FDAs BLA acceptance has triggered a $20 million milestone payment from Pierre Fabre Laboratories to Atara, with an additional $60 million milestone payment if approved by the FDA.

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FDA Sets Review Date for Cell Therapy for Post-Transplant Complication - Managed Healthcare Executive

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Exploring treatment options in cancer: Tumor treatment strategies - Nature.com