KarMMa-9 Study of Ide-Cel/Lenalidomide Maintenance in Newly Diagnosed Myeloma Discontinues Enrollment

Chip Baird

Enrollment in the phase 3 KarMMa-9 trial (NCT06045806), which is examining idecabtagene vicleucel (ide-cel; Abecma) plus lenalidomide (Revlimid) as maintenance therapy vs lenalidomide maintenance therapy in patients with newly diagnosed multiple myeloma with a suboptimal response to autologous stem cell transplantation (ASCT), will discontinue enrollment, according to an announcement from 2seventy bio.¹

“With a greatly improved newly diagnosed multiple myeloma treatment landscape and following our rigorous review of the business case for the KarMMa-9 study, we have decided to discontinue enrollment in this phase 3 study,” Chip Baird, chief executive officer of 2seventy bio, stated in a news release. “Ide-cel continues to show encouraging signs of growth with an expanded label in the third line and a differentiated safety profile. Consistent with our focus on capital allocation and creating value for all stakeholders, we anticipate this decision will conserve over $80 million in near-term expenditures and accelerate our path to breakeven in 2025. We will continue to look for ways to optimize our business for growth while remaining true to our mission of delivering more time for patients.”

Ide-cel is a BCMA-targeted genetically modified autologous CAR T-cell therapy. In April 2024, the FDA approved ide-cel for the treatment of adult patients with relapsed or refractory multiple myeloma following at least 2 prior lines of therapy, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody. The regulatory decision was supported by findings from the phase 3 KarMMa-3 trial (NCT03651128).^1,2

KarMMa-9 was an open-label trial that enrolled adult patients with newly diagnosed multiple myeloma who previously received induction therapy followed by high-dose chemotherapy and ASCT without subsequent consolidation or maintenance therapy. To be eligible for the study, patients needed to have received 4 to 6 cycles of induction therapy, including an IMiD and a (PI), with or without an anti-CD38 monoclonal antibody, and a single ASCT 80 to 120 days prior to consent. A documented partial response (PR) or very good PR at time of consent was required. Other key inclusion criteria consisted of an ECOG performance status of 1 or less, and recovery to grade 1 or less for any nonhematologic toxicities.³

Patients with central nervous system involvement and non-secretory multiple myeloma were excluded from the study.

In the experimental arm, lymphodepleting chemotherapy with fludarabine and cyclophosphamide was given prior to ide-cel, and patients then received lenalidomide maintenance. In the control arm, lenalidomide maintenance was given alone.

The primary end point was progression-free survival per independent review committee assessment. Secondary end points included overall survival, 12-month minimal residual disease (MRD) complete response (CR) rate, MRD CR rate, event-free survival, duration of response, CR rate, time to progression, and safety.

“Since we initiated the phase 3 KarMMa-9 study in newly diagnosed multiple myeloma based on the positive data generated in a similar patient population in the [phase 2] KarMMa-2 cohort 2c study [NCT03601078], the newly diagnosed multiple myeloma 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 of 2seventy bio, added in the news release.¹ “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 ide-cel. We would like to extend our deepest gratitude to the patients, their families, and the investigators and study staff who participated in this trial.”

References

1. 2seventy bio Provides Update on KarMMa-9 Study and Previews Anticipated Strong Third Quarter Revenue Performance. News release. 2seventy bioInc. September 25, 2024. Accessed September 25, 2024. https://ir.2seventybio.com/news-releases/news-release-details/2seventy-bio-provides-update-karmma-9-study-and-previews
2. US 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. News release. Bristol Myers Squibb. April 4, 2024. Accessed September 25, 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
3. 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 25, 2024. https://clinicaltrials.gov/study/NCT06045806