Afamitresgene autoleucel

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Afamitresgene autoleucel
Clinical data
Trade names Tecelra
Other namesMAGE-A4C1032T
AHFS/Drugs.com Monograph
License data
Routes of
administration 		Intravenous infusion
ATC code
  • None
Legal status
Legal status
Identifiers
UNII
KEGG

Afamitresgene autoleucel, sold under the brand name Tecelra is a T cell immunotherapy used for the treatment of synovial sarcoma. [1] [2] It is a T cell receptor (TCR) gene therapy. [3] It is administered as a single intravenous dose. [3]

Contents

The most common adverse reactions include cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema. [4]

Afamitresgene autoleucel was approved for medical use in the United States in August 2024. [2] [4] [5] Afamitresgene autoleucel is the first T cell receptor (TCR) gene therapy approved by the US Food and Drug Administration (FDA). [3]

Medical uses

Afamitresgene autoleucel is a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. [1] [4]

Afamitresgene autoleucel is an autologous T cell immunotherapy composed of a recipient's own T cells. [3] T cells in afamitresgene autoleucel are modified to express a T cell receptor that targets MAGE-A4, an antigen (substance that normally triggers the immune system) expressed by cancer cells in synovial sarcoma. [3]

Adverse effects

The US Food and Drug Administration (FDA) prescribing information includes a boxed warning for serious or fatal cytokine release syndrome, which may be severe or life-threatening. [3] [4]

The most common adverse reactions include cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema. [4] The most common grade 3 or 4 laboratory abnormalities include lymphocyte count decreased, neutrophil count decreased, white cell blood count decreased, red blood cell decreased, and platelet count decreased. [4]

Recipients may also exhibit immune effector cell-associated neurotoxicity syndrome (ICANS), an immune system-related syndrome that can occur following some immunotherapies, infections, secondary malignancies, or hypersensitivity reactions, and severe cytopenia (an abnormally low level of blood cells) for several weeks following lymphodepleting chemotherapy and infusion of afamitresgene autoleucel. [3]

History

The safety and effectiveness of afamitresgene autoleucel was evaluated in SPEARHEAD-1, cohort 1, a multicenter, single-arm, open-label clinical trial that enrolled HLA-A*02:01-03 and 06 allele positive participants with inoperable or metastatic synovial sarcoma who had received prior systemic therapy with either doxorubicin and/or ifosfamide and whose tumor expressed the MAGE-A4 tumor antigen. [3] [4] Participants received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. [4] Fifty-two participants with synovial sarcoma were enrolled and underwent leukapheresis, eight of whom did not receive afamitresgene autoleucel due to death (n=3), loss of eligibility prior to lymphodepleting chemotherapy (n=3), withdrawal by patient (n=1), and investigator decision (n=1). [4] Forty-five participants received lymphodepletion and one patient withdrew consent before treatment, for a total of 44 participants who received a single infusion of afamitresgene autoleucel. [4] Effectiveness was evaluated based on overall response rate and the duration of response to treatment with afamitresgene autoleucel. [3] Among the 44 participants in the trial who received afamitresgene autoleucel, the overall response rate was 43.2% and the median duration of response was six months. [3]

Society and culture

Afamitresgene autoleucel was approved for medical use in the United States under the accelerated approval pathway in August 2024. [2] [4] [6] The FDA granted the application for afamitresgene autoleucel regenerative medicine advanced therapy, priority review, and orphan drug designations. [4] The FDA granted the approval of Tecelra to Adaptimmune, LLC. [3]

Names

Afamitresgene autoleucel is the international nonproprietary name. [7]

Related Research Articles

<span class="mw-page-title-main">Soft-tissue sarcoma</span> Malignant tumor that develops in soft tissue

A soft-tissue sarcoma (STS) is a malignant tumor, a type of cancer, that develops in soft tissue. A soft-tissue sarcoma is often a painless mass that grows slowly over months or years. They may be superficial or deep-seated. Any such unexplained mass must be diagnosed by biopsy. Treatment may include surgery, radiotherapy, chemotherapy, and targeted drug therapy. Bone sarcomas are the other class of sarcomas.

This is a list of terms related to oncology. The original source for this list was the US National Cancer Institute's public domain Dictionary of Cancer Terms.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

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<span class="mw-page-title-main">Synovial sarcoma</span> Rare cancer of the extremities, often near joints or tendon sheaths

A synovial sarcoma is a rare form of cancer which occurs primarily in the extremities of the arms or legs, often in proximity to joint capsules and tendon sheaths. It is a type of soft-tissue sarcoma.

<span class="mw-page-title-main">Bi-specific T-cell engager</span> Class of artificial monoclonal antibodies

Bi-specific T-cell engager (BiTE) is a class of artificial bispecific monoclonal antibodies that are investigated for use as anti-cancer drugs. They direct a host's immune system, more specifically the T cells' cytotoxic activity, against cancer cells. BiTE is a registered trademark of Micromet AG.

Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.

Neuvenge, Lapuleucel-T, is a therapeutic cancer vaccine (TCV) in development by Dendreon (DNDN). It uses the "immunotherapy platform approach" first successfully demonstrated on the U.S. Food and Drug Administration (FDA)-approved TCV Provenge. It was first tested on breast cancer patients with tumors expressing HER2/neu, and is now scheduled to be tested on bladder cancer patients.

<span class="mw-page-title-main">Nivolumab</span> Anticancer medication

Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.

<span class="mw-page-title-main">Pembrolizumab</span> Pharmaceutical drug used in cancer treatment

Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody, more specifically a PD-1 Inhibitor, used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.

<span class="mw-page-title-main">Atezolizumab</span> Monoclonal anti-PD-L1 antibody

Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).

Avelumab, sold under the brand name Bavencio, is a fully human monoclonal antibody medication for the treatment of Merkel cell carcinoma, urothelial carcinoma, and renal cell carcinoma.

<span class="mw-page-title-main">Erdafitinib</span> Chemical compound

Erdafitinib, sold under the brand name Balversa, is an anti-cancer medication. It is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) used for the treatment of cancer. FGFRs are a subset of tyrosine kinases which are unregulated in some tumors and influence tumor cell differentiation, proliferation, angiogenesis, and cell survival. Astex Pharmaceuticals discovered the drug and licensed it to Janssen Pharmaceuticals for further development.

Axicabtagene ciloleucel, sold under the brand name Yescarta, is a medication used for the treatment for large B-cell lymphoma that has failed conventional treatment. T cells are removed from a person with lymphoma and genetically engineered to produce a specific T-cell receptor. The resulting chimeric antigen receptor T cells (CAR-Ts) that react to the cancer are then given back to the person to populate the bone marrow. Axicabtagene treatment carries a risk for cytokine release syndrome (CRS) and neurological toxicities.

Lisocabtagene maraleucel, sold under the brand name Breyanzi, is a cell-based gene therapy used to treat B-cell lymphomas, including follicular lymphoma.

<span class="mw-page-title-main">Selpercatinib</span> Chemical compound

Selpercatinib, sold under the brand name Retevmo among others, is a medication for the treatment of cancers in people whose tumors have an alteration in a specific gene. It is taken by mouth.

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Ciltacabtagene autoleucel, sold under the brand name Carvykti, is an anti-cancer medication used to treat multiple myeloma. Ciltacabtagene autoleucel is a BCMA -directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using the recipient's own T-cells, which are collected and genetically modified, and infused back into the recipient.

Tarlatamab, sold under the brand name Imdelltra, is an anti-cancer medication used for the treatment of extensive-stage small cell lung cancer. It is a bispecific T-cell engager that binds delta-like ligand 3 and CD3.

Obecabtagene autoleucel, sold under the brand name Aucatzyl, is an anti-cancer medication used for the treatment of acute lymphoblastic leukemia. It is a CD19-directed genetically modified autologous T-cell immunotherapy.

References

  1. 1 2 3 "Tecelra- afamitresgene autoleucel injection, suspension". DailyMed. 3 August 2024. Retrieved 15 August 2024.
  2. 1 2 3 4 "Tecelra (afamitresgene autoleucel)". U.S. Food and Drug Administration. 1 August 2024. Archived from the original on 5 August 2024. Retrieved 5 August 2024.
  3. 1 2 3 4 5 6 7 8 9 10 11 "FDA Approves First Gene Therapy to Treat Adults with Metastatic Synovial Sarcoma". U.S. Food and Drug Administration (FDA). 2 August 2024. Retrieved 8 August 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  4. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA grants accelerated approval to afamitresgene autoleucel for unresectable or metastatic synovial sarcoma". U.S. Food and Drug Administration (FDA). 2 August 2024. Archived from the original on 4 August 2024. Retrieved 5 August 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  5. ↑ "Adaptimmune Receives U.S. FDA Accelerated Approval of Tecelra (afamitresgene autoleucel), the First Approved Engineered Cell Therapy for a Solid Tumor" (Press release). Adaptimmune. 2 August 2024. Archived from the original on 4 August 2024. Retrieved 5 August 2024– via Business Wire.
  6. ↑ "Cancer Accelerated Approvals". U.S. Food and Drug Administration (FDA). 1 October 2024. Retrieved 6 December 2024.
  7. ↑ World Health Organization (2020). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 84". WHO Drug Information. 34 (3). hdl: 10665/340680 .

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