FDA Approval Sought for Talquetamab in Relapsed/Refractory Multiple Myeloma

FDA

A biologics license application (BLA) has been submitted to the FDA for talquetamab for the treatment of patients with relapsed or refractory multiple myeloma, according to an announcement from Janssen.¹

The BLA for the first-in-class, off-the-shelf T-cell redirecting bispecific antibody is supported by data from the phase 1/2 MonumenTAL-1 trial (NCT03399799). Data presented at the 2022 ASH Annual Meeting showed that patients treated with talquetamab at 0.4 mg/kg every week achieved an overall response rate (ORR) of 74.1%, and those treated at a 0.8 mg/kg dose every 2 weeks experienced an ORR of 73.1%.²

In the 0.4 mg/kg cohort, the stringent complete response (sCR) rate was 23.8%, the CR rate was 9.8%, the very good partial response (VGPR) rate was 25.9%, and the PR rate was 14.7%. In the 0.8 mg/kg cohort, the rates of sCR, CR, VGPR, and PR were 20.0%, 12.4%, 24.8%, and 15.9%.

“Despite the therapies that have been developed for the treatment of multiple myeloma, there remains persistent unmet needs for patients who relapse or become refractory,” Peter Lebowitz, MD, PhD, head, Global Therapeutic Area, Oncology, Janssen Research & Development, stated in a news release. “Through our discovery and development of talquetamab, a novel GPRC5DxCD3 bispecific antibody, we remain relentlessly committed to the investigation of innovative therapies for patients and oncologists. We look forward to working closely with the FDA in their review of the talquetamab submission.”

Talquetamab targets both CD3 and GPRC5D, which is a novel target highly expressed on multiple myeloma cells.

MonumentTAL-1 enrolled adult patients with measurable multiple myeloma. In phase 1, patients were required to have progression on or intolerance to all established therapies, as well as an ECOG performance status of 0 or 1. In phase 2, patients needed to have received at least 3 prior lines of therapy that included a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, and have an ECOG performance status of 0 to 2.

Patients who did not receive prior T-cell redirection therapy were enrolled into 1 of 2 cohorts to receive subcutaneous talquetamab at 0.4 mg/kg every week or 0.8 mg/kg every 2 weeks. Prior treatment with an anti-BCMA antibody-drug conjugate was permitted for patients in these 2 cohorts. Patients who had prior T-cell redirection therapy were enrolled into a third cohort, where they received either talquetamab at 0.4 mg/kg every week or 0.8 mg/kg every 2 weeks.

The primary end point of the study was to determine the efficacy and safety of the 2 doses of talquetamab.

Among patients who were T-cell redirection therapy naïve in the 0.4 mg/kg cohort (n = 143) and the 0.8 mg/kg cohort (n = 145), the median age was 67 years. Most patients were male and White. In the 0.4 mg/kg cohort, 23.1% of patients had extramedullary plasmacytomas and 31.1% had high-risk cytogenetics. In the 0.8 mg/kg cohort, the rates of extramedullary plasmacytomas and high-risk cytogenetics were 26.9% and 24.3%, respectively.

All patients in both cohorts were triple-class exposed, and the majority were penta-drug exposed. Additionally, 74.1% and 69% of patients were triple-class refractory in the 0.4 mg/kg and 0.8 mg/kg cohorts, respectively, and the rates of patients who were penta-drug refractory were 29.4% and 23.4%, respectively.

Additional data showed that the median progression-free survival was 7.5 months (95% CI, 5.7-9.4) in the 0.4 mg/kg cohort and 11.9 months (95% CI, 8.4-not estimable) in the 0.8 mg/kg cohort.

The most common high-grade hematologic adverse effects (AEs) were cytopenias. The most common grade 3/4 hematologic AEs were anemia (31.5% in the 0.4 mg/kg cohort and 24.8% in the 0.8 mg/kg cohort), neutropenia (30.8% and 22.1%), lymphopenia (25.9% and 25.5%), and thrombocytopenia (20.3% and 16.6%).

Infections were reported in 57.3% and 50.3% of patients in the 0.4 mg/kg and 0.8 mg/kg cohorts, respectively, and 16.8% and 11.7% of infections were high-grade.

Most instances of cytokine release syndrome (CRS) were grade 1/2, and they were primarily identified during step-up dosing and the first full dose. Any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 10.7% and 10.1% of patients in the 0.4 mg/kg and 0.8 mg/kg arms, respectively, and the majority of ICANS events were grade 1/2.

In the 0.4 mg/kg arm, the most common any-grade, nonhematologic AEs included CRS (79.0%), skin AEs (55.9%), and nail AEs (51.7%), with high-grade AEs including fatigue (3.5%) and pyrexia (2.8%). In the 0.8 mg/kg cohort, any-grade AEs included CRS (72.4%), skin AEs (67.6%), and dysgeusia (46.2%), with high-grade toxicities including rash (5.5%) and dysphagia (2.1%).

References

1. Janssen submits biologics license application to U.S. FDA for talquetamab for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. December 9, 2022. Accessed December 9, 2022. http://bit.ly/3HLmFMF
2. Chari A, Touzeau C, Schinke C, et al. Talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): phase 1/2 results from MonumenTAL-1. Blood. 2022;140(suppl 1):384-387. doi:10.1182/blood-2022-159707