Ide-Cel to Be Evaluated in Newly Diagnosed Multiple Myeloma

2seventy bio’s idecabtagene vicleucel (ide-cel; Abecma), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy which was previously approved by the FDA for adults with relapsed or refractory (r/r) multiple myeloma (MM) who have been treated with at least 4 prior lines of therapy, will be tested in a new clinical trial (KarMMa-9) for patients with newly diagnosed MM who have a suboptimal response to transplant.

The announcement came after 2seventybio, which is working in partnership with Bristol Myers Squibb, announced top-line results from KarMMa-3, a phase 3 clinical trial (NCT03651128) evaluating the efficacy and safety of ide-cel in comparison to standard combination regimens for patients with r/r MM who received 2 to 4 prior lines of therapy and were refractory to the last regimen. The results, which were provided by an independent review committee that conducted a pre-specified interim analysis, demonstrated that ide-cel was associated with a statistically significant improvement in progression-free survival (PFS) and an improvement in overall response rate (ORR) compared with standard regimens. Safety-related results were consistent with ide-cel’s previously established safety profile demonstrated in the earlier phase 2 KarMMa(NCT03361748)clinical trial. The data from KarMMa-3 will be presented at a future medical meeting.

“Our focus at 2seventy is giving as much time as possible to patients who are battling cancer,” Steve Bernstein, chief medical officer, 2seventy bio, said in a statement. "We are moving rapidly to expand our clinical study program to determine utility of Abecma in newly diagnosed MM patients with suboptimal response to transplant. This population currently makes up more than half of MM patients receiving transplant. Given the efficacy data from our collective KarMMa studies and well-established and predictable safety profile seen in studies replicated in the real-world, we believe there is tremendous potential for Abecma to help some of these patients earlier in their treatment path.”

The on-going multicenter, open-label, 2-arm KarMMa-3 trial is estimated to enroll 381 patients aged 18 years or older with r/rMM who have received at least 2 but no more than 4 prior regimens of therapy for MM, and who were refractory to the last treatment regimen. Prior treatment is required to have included daratumumab, a proteasome inhibitor, and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles. Additionally, participants must have achieved at least a minimal response to at least 1 prior treatment regimen, have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and have recovered to grade 1 or baseline from non-hematologic toxicities that resulted from prior treatment, with the exception of alopecia and grade 2 peripheral neuropathy.

Patients in Arm A receive a dose of ide-cel between 150x10⁶ and 450x10⁶ cells following lymphodepleting chemotherapy. Patients in Arm B receive 1 of 5 standard regimens based on the patient’s most recent treatment and the investigator’s discretion. Approximately 2 thirds of participants are randomly assigned to Arm A while approximately 1 third are assigned to Arm B. The primary end point is PFS. Secondary end points include overall survival, event-free survival, ORR, minimal residual disease, complete response rate, duration of response, time to response, the number of participants who experience adverse events, time to next antimyeloma treatment, PFS after next line therapy, pharmacokinetic analyses, and patient-reported outcomes. The study’s estimated completion date is September 22, 2026.

"Given the performance over other treatment options, autologous stem cell transplant will most likely continue to be the standard of care in patients newly diagnosed with multiple myeloma who are eligible,” Nikhil Munshi, MD, director of Basic and Correlative Science, Jerome Lipper Multiple Myeloma Center, Kraft Family Chair, senior physician, Dana-Farber Cancer Institute, professor of medicine, Harvard Medical School, added to the statement. “However, a high unmet clinical need remains, specifically in patients who have a suboptimal response to transplant. The investigation of a well-established CAR T cell therapy, such as Abecma, in the newly diagnosed multiple myeloma treatment paradigm will be an important next step.”

REFERENCE

2seventy bio announces plans to initiate KarMMa-9 study of Abecma (idecabtagene vicleucel) in newly diagnosed multiple myeloma patients. News release. 2seventy bio, Inc. September 7, 2022. https://ir.2seventybio.com/news-releases/news-release-details/2seventy-bio-announces-plans-initiate-karmma-9-study-abecma