Bristol Myers Squibb and 2seventy bio Halt KarMMa-9 Trial in Patients with Newly Diagnosed Multiple Myeloma

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Bristol Myers Squibb (BMS) and 2seventy bio announced the discontinuation of enrollment in the Phase III KarMMa-9 trial (NCT06045806) evaluating Abecma (idecabtagene vicleucel) in newly diagnosed multiple myeloma (NDMM) patients. The companies stated that changes in treatment protocols have reduced the eligible patient population for the trial, as an evolving therapeutic landscape has produced stronger and more prolonged induction therapies for the disease.¹

In a press release, BMS stated that the KarMMa-9 trial has been open for more than a year in 18 countries; however, just 10% of the study population has been enrolled to date.

“Investigators indicate that due to advances in induction therapies, a significant majority—upwards of 70%—of patients with [NDMM] are now achieving a complete response or better following transplant,” Anne Kerber, senior vice president, head of Late Clinical Development, Hematology, Oncology and Cell Therapy, BMS, said in a press release. “We celebrate this progress for patients while also recognizing that it reduces the eligible patient population for, and viability of, the KarMMa-9 trial.”¹

Abecma is a chimeric antigen receptor (CAR) T-cell therapy that attaches to BCMA on the surface of multiple myeloma cells, which prompts the proliferation of the CAR T cells, leading to cytokine secretion and cytolytic elimination of BCMA-expressing cells.

In March 2024, the FDA Oncologic Drugs Advisory Committee (ODAC) voted that Abecma shows a favorable benefit/risk profile for patients with triple-class exposed relapsed or refractory multiple myeloma.² The vote was based on positive findings from the pivotal Phase III KarMMa-3 study.

In April 2024, the FDA approved Abecma to treat adult patients with relapsed or refractory multiple myeloma who were previously administered two or more lines of therapy that included an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.³ The approval expanded the indication for Abecma to earlier lines of treatment in patients with disease that relapsed or became refractory after receiving three primary treatment classes after two prior lines of therapy.

The open-label KarMMa-9 trial enrolled adults with NDMM previously administered induction therapy followed by high-dose chemotherapy and ASCT without subsequent consolidation or maintenance therapy. Eligibility criteria for the study included having received four to six cycles of induction therapy, including an IMiD and a PI, with or without an anti-CD38 monoclonal antibody, and a single autologous stem cell transplant (ASCT) 80 to 120 days before consent. Patients were also required to have a documented partial response (PR) or very good PR at the time of consent, an ECOG performance status of 1 or less, and recovery to grade 1 or under for nonhematologic toxicities.⁴

BMS and 2seventy bio stated that they will work with trial investigators to evaluate appropriate next steps for those currently enrolled in KarMMa-9.

“Since we initiated the Phase III KarMMa-9 study in NDMM based on the positive data generated in a similar patient population in the KarMMa-2 cohort 2c study, the NDMM treatment landscape has improved considerably with the increasing use of quadruplet therapy induction, incorporation of more aggressive consolidation therapies, and the ongoing optimization of maintenance therapy regimens,” Anna Truppel-Hartmann, chief medical officer, 2seventy bio, said in a press release. “As a result, there are considerably fewer eligible patients than when the study was first designed. We celebrate this progress in treatment options for patients and will continue to focus on serving patients with a high unmet need who will benefit most from Abecma. We would like to extend our deepest gratitude to the patients, their families, and the investigators and study staff who participated in this trial.”⁵

References

1. Bristol Myers Squibb and 2seventy bio Provide Update on KarMMa-9 Trial of Abecma in Patients with Newly Diagnosed Multiple Myeloma. News release. Bristol Myers Squibb. September 25, 2024. Accessed September 26, 2024. https://news.bms.com/news/details/2024/Bristol-Myers-Squibb-and-2seventy-bio-Provide-Update-on-KarMMa-9-Trial-of-Abecma-in-Patients-with-Newly-Diagnosed-Multiple-Myeloma/default.aspx

2. FDA Advisory Committee Votes in Favor of Bristol Myers Squibb’s and 2seventy bio’s Abecma for Triple-Class Exposed Multiple Myeloma in Earlier Lines of Therapy. News release. March 15, 2024. Accessed September 26, 2024. https://news.bms.com/news/details/2024/FDA-Advisory-Committee-Votes-in-Favor-of-Bristol-Myers-Squibbs-and-2seventy-bios-Abecma-for-Triple-Class-Exposed-Multiple-Myeloma-in-Earlier-Lines-of-Therapy/default.aspx

3. U.S. FDA Approves Bristol Myers Squibb and 2seventy bio’s Abecma for Triple-Class Exposed Relapsed or Refractory Multiple Myeloma After Two Prior Lines of Therapy. Bristol Myers Squibb. News release. April 5, 2024. Accessed September 26, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-FDA-Approves-Bristol-Myers-Squibb-and-2seventy-bios-Abecma-for-Triple-Class-Exposed-Relapsed-or-Refractory-Multiple-Myeloma-After-Two-Prior-Lines-of-Therapy/default.aspx

4. A study to compare the efficacy and safety of idecabtagene vicleucel with lenalidomide maintenance therapy versus lenalidomide maintenance therapy alone in adult participants with newly diagnosed multiple myeloma who have suboptimal response after autologous stem cell transplantation (KarMMa-9). ClinicalTrials.gov. Updated September 5, 2024. Accessed September 26, 2024. https://clinicaltrials.gov/study/NCT06045806

5. 2seventy bio Provides Update on KarMMa-9 Study and Previews Anticipated Strong Third Quarter Revenue Performance. News release. September 25, 2024. Accessed September 26, 2024. https://ir.2seventybio.com/news-releases/news-release-details/2seventy-bio-provides-update-karmma-9-study-and-previews