Phase 2 Studies Investigate Combination Therapies, BCMA in Patients With Relapsed/Refractory Multiple Myeloma

Researchers are conducting phase 2 trials to investigate combination therapies, such as B-cell maturation antigen (BCMA), for patients with multiple myeloma (MM). In the MagnetisMM-4 trial, investigators are running an umbrella study of elranatamab combined with the anticancer treatments nirogacestat or lenalidomide with dexamethasone.¹

The IMPEDE trial involves 3 phases to test isatuximab in combination with pomalidomide, elotuzumab, and dexamethasone in patients with relapsed/refractory MM who have undergone at least 2 prior lines of therapy.²

Finally, another phase 2 study is investigating venetoclax with carfilzomib and dexamethasone in patients with relapsed/refractory MM.³

MagnetisMM-4 Trial: Elranatamab Plus Nirogacestat or Lenalidomide and Dexamethasone

The MagnetisMM-4 trial (ClinicalTrials.gov Identifier: NCT05090566) aims to determine the recommended phase 2 dose and clinical benefit of elranatamab in combination with other anticancer therapies.¹

Elranatamab is a bispecific antibody that targets BCMA and CD3 on T cells, and activates and redirects the T-cell-mediated immune response against MM.⁴ Prior study results have shown that elranatamab induced durable clinical responses for patients with relapsed or refractory MM. The drug is also under investigation in the MagnetisMM-3 (ClinicalTrials.gov Identifier: NCT0469359) and MagnetisMM-5 (ClinicalTrials.gov Identifier: NCT05020236) trials.

This open-label trial is recruiting an estimated 105 patients with relapsed/refractory MM who have undergone at least 3 prior lines of therapy, including at least 1 immunomodulatory drug, 1 proteasome inhibitor, and 1 anti-CD38 antibody.¹ Eligible participants must also have measurable disease, an ECOG performance status of 0 or 1, and no prior treatment with a BCMA-bispecific antibody or BCMA-directed therapy.

The study is divided into 2 parts: Sub-Study A and Sub-Study B. Sub-Study A will administer elranatamab plus nirogacestat, whereas Sub-Study B will treat patients with elranatamab plus lenalidomide and dexamethasone.

The primary endpoint of the study is to determine any dose-limiting toxicities for either combination as well as to assess the objective response rate (ORR). Key secondary outcomes include the complete response rate, time to response, and duration of response.

This trial is sponsored by Pfizer.

IMPEDE Trial Assesses Isatuximab, Pomalidomide, Elotuzumab, and Dexamethasone

The multicenter, open-label IMPEDE trial (ClinicalTrials.gov Identifier: NCT04835129) has 3 phases to assess combination therapy with isatuximab, pomalidomide, dexamethasone, and elotuzumab in patients with relapsed/refractory MM who have undergone at least 2 prior lines of therapy.² The phases include a 28-day screening phase, a treatment phase of 28-day cycles of isatuximab with elotuzumab, pomalidomide, and dexamethasone, and a follow-up phase.

The study is further divided into a safety run-in phase and expansion phase. The safety run-in includes 6 patients to assess any dose-limiting toxicities associated with the combination, and the expansion phase will enroll up to 47 additional participants to determine whether adding isatuximab to elotuzumab, pomalidomide, and dexamethasone would be a safe and effective combination in patients with relapsed/refractory MM.

Adult patients who are eligible for this study must have received at least 2 prior therapies that included lenalidomide and a proteasome inhibitor combined or in different regimens. The primary endpoints for the study include the rates of complete and partial responses.

This trial is sponsored by the Medical College of Wisconsin.

Study of Venetoclax Plus Carfilzomib and Dexamethasone

This open-label dose escalation study (ClinicalTrials.gov Identifier: NCT02899052) is evaluating the safety and efficacy of venetoclax in combination with carfilzomib and dexamethasone in patients with relapsed/refractory MM who have received 1 to 3 prior lines of therapy.³

The investigators aim to enroll 120 participants who have an ECOG performance status of 2 or lower and positive t(11;14) translocation as determined by an analytically validated fluorescent in situ hybridization assay. Eligible patients must also have received at least 1 prior line of therapy without a history of other malignancies.

Primary endpoints of the phase 2 trial include assessing the number of adverse events, the rate of very good partial response or better, and the ORR. The investigators will also determine the complete response or better rate. Key secondary endpoints include progression-free survival, duration of overall response, and time to progression.

The trial is sponsored by AbbVie.

References

1. ClinicalTrials.gov. MagnetisMM-4: umbrella study of elranatamab (PF-06863135) in combination with anti-cancer treatments in multiple myeloma. NCT05090566. Accessed April 4, 2023.
2. ClinicalTrials.gov. Isatuximab, pomalidomide, elotuzumab and dexamethasone in relapsed and/or refractory multiple myeloma (IMPEDE). NCT04835129. Accessed April 4, 2023.
3. ClinicalTrials.gov. Study of venetoclax in combination with carfilzomib and dexamethasone in participants with relapsed or refractory multiple myeloma (MM). NCT02899052. Accessed April 4, 2023.
4. Raje N, Bahlis NJ, Costello C, et al. Elranatamab, a BCMA targeted T-cell engaging bispecific antibody, induces durable clinical and molecular responses for patients with relapsed or refractory multiple myeloma. Presented at ASH 2022. December 10-13, 2022. Abstract 158.