3 Cancer Drugs Expected to Receive FDA Approval in August 2024

The following are the 3 oncology drugs on which the FDA (United States Food and Drug Administration) is expected to make a decision in August 2024:

1. Afamitresgene autoleucel (afami-cel) for advanced synovial sarcoma,
2. Linvoseltamab for relapsed or refractory multiple myeloma, and
3. Axatilimab for chronic graft-versus-host disease.

Afami-cel for Advanced Synovial Sarcoma

The FDA has accepted the biologics license application (BLA = biologics license application) for afami-cel for priority review for the treatment of advanced synovial sarcoma. Afami-cel is an autologous T-cell therapy developed to target cancer cells in solid tumors that express the MAGE A4 protein.

Autologous T-cell therapy involves collecting a patient's own immune cells (T cells), genetically modifying them in a laboratory, and then returning them to the patient. This treatment enables T cells to recognize and destroy cancer cells more effectively. Although it has been used effectively for blood and lymphatic cancers for years, effective cellular therapies for solid cancers arising in tissues and organs are only just beginning to emerge.

The BLA application is supported by data from the phase 2 SPEARHEAD-1 trial , specifically cohort 1. This study was designed to evaluate afami-cel in 44 patients with metastatic or unresectable synovial sarcoma and 8 patients with myxoid/round-cell liposarcoma who were HLA-A*02 eligible and MAGE A4 positive.

Related topic: Immunotherapy in Sarcoma – Current Evidence and Promising Strategies

Patients had received a median of 3 previous lines of treatment. All patients in the study received a single dose of afami-cel, and 20 patients received bridging therapy.

Among patients with synovial sarcoma

• The response rate was 39% , and the median duration of response was 11.6 months.
• Median progression-free survival was 3.8 months , and
• median overall survival was 16.9 months .

Across the entire patient group, the most common grade 3 or higher treatment-related adverse events were lymphopenia (96%), neutropenia (85%), and leukopenia (81%).

The image below illustrates the cellular process through which an engineered T-cell receptor (TCR) therapy such as afami-cel works.

1. Identifying the target protein: Afami-cel recognizes a target protein such as MAGE A4, which is found particularly in cancer cells and only rarely in normal cells.
2. Processing the protein: The target protein is broken down by the proteasome inside the cell into peptide fragments.
3. Forming the HLA-peptide complex: The processed peptide fragments combine with HLA (Human Leukocyte Antigen) molecules on the cell surface. This complex is transported to the cell surface for recognition by T cells.
4. Recognition and interaction through the TCR: T-cell receptors (TCRs) on the surface of the engineered T cells recognize this HLA-peptide complex and bind specifically to the cancer cells.
5. Action against cancer cells: Binding of TCRs to the HLA-peptide complex triggers the activation of T cells to destroy cancer cells. This activation results in cancer cell death, thereby shrinking or eliminating the tumor.

Linvoseltamab for Relapsed/Refractory Multiple Myeloma

The FDA is reviewing the biologics license application for linvoseltamab for the treatment of adults with relapsed or refractory multiple myeloma. The application is supported by data from the phase 1/2 LINKER-MM1 trial .

This study was designed to evaluate linvoseltamab, a BCMA-CD3–targeted bispecific antibody, in patients with relapsed or refractory multiple myeloma whose disease had progressed after at least 3 prior lines of treatment, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody.

The study included 117 evaluable patients, and the median follow-up was 11.1 months.

• The objective response rate was 71%,
• 46% of patients achieved a complete response or better, and
• 62% achieved a very good partial response or better.
• The median time to complete response was 7.9 months, and the median time to partial response was 2.6 months.

Median duration of response, progression-free survival, and overall survival were not reached. The probability of maintaining a response at 12 months was 78%, the probability of survival at 12 months was 74.5%, and the probability of being alive and progression-free at 12 months was 68.8%.

The most common treatment-related adverse events were cytokine release syndrome (46.2%), neutropenia (41.0%), and anemia (38.5%).

Axatilimab for Chronic GvHD

The FDA is reviewing axatilimab, a monoclonal antibody targeting CSF-1R, for the treatment of chronic GvHD in patients who have received at least 2 previous lines of systemic therapy.

The application is supported by data from the phase 2 AGAVE-201 trial. This study included 241 adult and pediatric patients who had received 4 previous lines of systemic treatment for GvHD.

Patients were randomly assigned to receive axatilimab at 0.3 mg/kg every 2 weeks (80 patients), 1 mg/kg every 2 weeks (81 patients), or 3 mg/kg every 4 weeks (80 patients).

During the first 6 treatment cycles,

• The overall response rate was 74% in the 0.3 mg/kg arm, 67% in the 1 mg/kg arm, and 50% in the 3 mg/kg arm.

The most common adverse events across the arms were fatigue, headache, and COVID-19.