BMS and 2seventy bio Axe Trial for Ide-Cel in Newly Diagnosed Multiple Myeloma
Enrollment difficulties were cited as the reason for discontinuing recruitment activities for KarMMa-9.
Bristol Myers Squibb (BMS) and 2seventy bio have discontinued recruitment activities for the phase 3 KarMMa-9 clinical trial (NCT06045806), which was intended to evaluate idecabtagene vicleucel (ide-cel; marketed as Abecma) in combination with lenalidomide maintenance against lenalidomide maintenance alone for the treatment of newly diagnosed multiple myeloma (NDMM) in patients who had a suboptimal response following autologous stem cell transplant.1
The companies cited enrollment difficulties as the main reason for the decision, pointing out that the study has been open for recruitment in 18 countries for more than 1 year, but has only gathered 10%of the planned study population in that time, even in the face of actions meant to facilitate enrollment that were taken with support from investigators and study staff. Furthermore, the companies explained that although the trial was originally designed with reference to ide-cel's favorable benefit/risk profile seen in cohort 2c of the phase 2 KarMMa-2 clinical trial (NCT03601078), changes in the treatment landscape since then may have rendered this approach obsolete. Namely, NDMM has begun to be treated with more intense and prolonged induction therapies, leaving a smaller eligible patient population for a design like that of KarMMa-9.
“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, MD, the senior vice president and head of late clinical development, hematology, oncology, and cell Therapy, at BMS, said in a statement.1 “We celebrate this progress for patients while also recognizing that it reduces the eligible patient population for, and viability of, the KarMMa-9 trial.”
The companies stated their intent to collaborate with investigators on a plan for how to move forward with the patients already enrolled and participating in the trial. In addition, they reaffirmed their position that ide-cel still has an important place in the landscape of care for MM and that efforts to bring the therapy to more patients in general will continue.
In November 2023, BMS reported that the Prescription Drug User Fee Act (PDUFA) action date for a supplemental biologics license application (sBLA) for ide-cel was pushed back by the FDA’s Oncologic Drugs Advisory Committee (ODAC) from December 16, 2023, to an unspecified later date.2 The sBLA was submitted with the intention of expanding ide-cel from its then-current FDA-approved indication, which covered adults with triple-class exposed relapsed/refractory (r/r) MM who have received 4 or more previous lines of treatment, to earlier-line settings. The pushing of the PDUFA date was made to accommodate advisory committee (AdComm) meeting.
On April 5, 2024, the FDA approved ide-cel for an expanded indication for patients with r/r MM who have been treated with 2 or more prior lines of therapy including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.3 The agency’s decision was made based on data from the phase 3 KarMMa-3 clinical trial (NCT03651128). Patients treated with ide-cel in the study had progression-free survival (PFS) ranging from 11.8 to 16.1 months (median, 13.3) compared with patients treated with standard of care (SOC) who had PFS ranging from 2.4 to 5.9 months (median, 4.4; hazard rate, 0.49 [95% CI, 0.28-0.65]; P <.0001), according to data presented at the 2023 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Orlando, Florida, February 15-19, 2023. Furthermore, patients in the ide-cel arm had an overall response rate of (95% CI, 66-77) while the ORR for patients in the SOC arm was 42% (95% CI, 33-50).
“The results of the KarMMa-3 study are remarkable, especially given the historic outcomes with standard regimens for these patients with relapsed or refractory disease,” Al-Ola A. Abdallah, MD, a clinical associate professor and the clinical director of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas, and the chair of the US Myeloma Innovations Research Collaborative, said in an April 2024 statement.3 “With this approval, these patients now have an opportunity to be treated at an earlier line of therapy with a potentially transformative therapy that offers significantly improved progression-free survival for this difficult-to-treat disease that has had no established treatment approach.”
