FDA Oncologic Drugs Advisory Committee (ODAC) will review Abecma (idecabtagene vicleucel) and Carvykti (ciltacabtagene) applications to broaden the labels for use in multiple myeloma early lines of treatment
On March 15, 2024, FDA Oncologic Drugs Advisory Committee (ODAC) will review BLA for Bristol Myers Squibb/2seventybio’s Abecma (idecabtagene vicleucel) and Johnson & Johnson/Legend’s Carvykti (ciltacabtagene) to broaden the labels for use of the agents in multiple myeloma to early lines of treatment.
Summary:
The focus of the discussion will be on the overall survival data in the pivotal trials (CARTITUDE-4 and KarMMa-3) for each application. Both sponsors, Bristol/2seventybio for Abecma and J&J/Legend for Carvykti, had planned ODAC reviews to expand the labels for early lines of treatment in multiple myeloma. The FDA's mention of a "general discussion focused on the overall survival data" suggests an examination of issues raised in a recent public workshop on the role of overall survival analysis in studies where it is not the primary endpoint. Additionally, the reviews will address uncertainties in overall survival in the context of relatively short-term trials and recent label updates in the CAR-T class regarding the risk of secondary malignancies. The formal scheduling of the meeting ensures that the reviews should not face further delays even in the event of a partial government shutdown in early March.
From the most recent FDA-AACR-ASA Workshop: Overall Survival in Oncology Clinical Trials, the FDA suggested that regardless of exploratory evaluation or formal testing for OS, studies should be designed to adequately assess OS to inform evaluation of patient safety and product benefit-risk. The agency adds that trials can include thresholds for harm and may be used to inform decision-making, based on a variety of considerations such as disease setting, feasibility for obtaining long-term OS data, rate of mortality, physician/patient input, known toxicities and other available data. It would be interesting to see how this ODAC will discuss the clinical benefit of Abecma and Carvykti's primary endpoint despite the lack of sufficient OS data and how it can inform benefit or harm to patients.
Background:
Abecma –
- Indicated for the treatment of adult patients with r/r multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.
- sBLA - The proposed indication is for the treatment of adult patients with relapsed or refractory multiple myeloma who have received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
Carvykti –
- Indicated for the treatment of adult patients with r/r multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.
- sBLA - The proposed indication for this product is for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least one prior line of therapy, including a proteasome inhibitor, and an immunomodulatory agent, and are refractory to lenalidomide.
This ODAC meeting will provide learnings for conducting confirmatory studies to support an sBLA for a new indication, which is relevant to Gilead/Kite’s product development of CAR-T therapy. In both cases, overall survival data will be the focus of the discussions. The benefits and risks of CAR-T class concerning secondary malignancies may also be discussed in the meeting.
Source:
FDA-AACR-ASA Workshop: Overall Survival in Oncology Clinical Trials