FDA Approves Talquetamab for Relapsed/Refractory Multiple Myeloma

FDA

The FDA has granted accelerated approval to talquetamab-tgvs (Talvey) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.

The regulatory decision was supported by data from the phase 2 MonumenTAL-1 trial (NCT04634552), which showed that patients who had received at least 4 prior lines of therapy and were not exposed to prior T-cell redirection therapy (n = 187) experienced meaningful overall response rates (ORRs). Patients treated with subcutaneous talquetamab at biweekly doses of 0.8 mg/kg achieved an ORR of 73.6% (95% CI, 63.0%-82.4%). Fifty-eight percent of patients experienced a very good partial response (VGPR) or better, including a complete response (CR) or better rate of 33%.

Patients treated at a weekly dose of 0.4 mg/kg expeirenced an ORR of 73.0% (95% CI, 63.2%-81.4%), including 57% with a VGPR or better and 35% with a CR or better. 

The median duration of response (DOR) was not reached in the 0.8 mg/kg cohort, and the median DOR was 9.5 months in the 0.4 mg/kg cohort. Among patients in the 0.8 mg/kg group, an estimated 85% of responders maintained response for at least 9 months.

"The clinically meaningful efficacy and safety profile observed with talquetamab in heavily pretreated patients in this clinical trial, which included patients treated with prior BCMA-targeted bispecific or CAR-T cell therapy, has been notable," Ajai Chari, MD, director of the Multiple Myeloma Program and professor of clinical medicine at the University of California, San Francisco, stated in a news release. "Patients at this stage of disease have a poor prognosis. Talquetamab as a first-in-class therapy is a new option for patients with this difficult-to-treat blood cancer."

MonumenTAL-1 was a single-arm, open-label, multicohort, multicenter, dose-escalation, phase 1 (NCT03399799) and phase 2 (NCT04634552) trial. Phase 1 evaluated the safety and efficacy of talquetamab in adult patients with relapsed/refractory multiple myeloma who received 3 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Patients were excluded if they received prior T-cell redirection therapy within 3 months of enrollment, had prior grade 3 or higher cytokine release syndrome (CRS) related to any T-cell redirection therapy, underwent an autologous stem cell transplant within the past 12 weeks, received an allogenic stem cell transplant within the past 6 months, had an ECOG performance status of 3 or higher, had a stroke or seizure within the past 6 months, had central nervous system involvement, or had clinical signs of meningeal involvement of multiple myeloma.

In phase 2, subcutaneous talquetamab was evalauted in patients with relapsed/refractory multiple myeloma at the recommended phase 2 doses of 0.4 mg/kg per week and 0.8 mg/kg every two weeks.

ORR and DOR were assessed by an independent review committee per International Myeloma Working Group criteria.

Phase 2 also included 32 patients who were exposed to a prior bispecific antibody or CAR-T cell therapy—including 94% who had a prior BCMA-directed therapy—and had received at least 4 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. These patients received talquetamab at 0.4 mg/kg per week, and at a median follow-up of 10.4 months, the ORR was 72% (95% CI, 53%-86%). An estimated 59% of responders maintained response for at least 9 months.

Regarding safety, talquetamab includes a box warning for CRS and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome.

During MonumenTAL-1, the most common adverse effects (AEs) reported in at least 20% of patients included pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. Grade 3 or 4 laboratory abnormalities that occurred in at least 30% of patients consisted of decreased lymphocyte count, decreased neutrophil count, decreased white blood cell , and decreased hemoglobin.

The most common non-hematologic AEs included oral toxicities (any-grade, 80%; grade 3, 2.1%). The most common any-grade oral toxicities consisted of dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%).

Sixty-two percent of patients experienced weight loss, including 29% with grade 2 weight loss and 2.7% with grade 3 weight loss.

The rate of serious infections was 16%, and fatal infections occurred in 1.5% of patients. Seventeen percent of patients experienced grade 3 or 4 serious infections. Thirty-five percent of patients experienced grade 3 or 4 decreased neutrophil count, and 22% had decreased platelet counts. Additionally, skin reactions were obsereved in 62% of patients, including 0.3% with grade 3 skin reactions.

Nine percent of patients permanently discontinued talquetamab due to AEs.

WATCH: Ajai Chari, MD, of UCSF Helen Diller Family Comprehensive Cancer Center, discusses the significance of the FDA approval of talquetamab in patients with relapsed/refractory multiple myeloma.

Reference

U.S. FDA approves Talvey (talquetamab-tgvs), a first-in-class bispecific therapy for the treatment of patients with heavily pretreated multiple myeloma. News release. Janssen. August 10, 2023. Accessed August 10, 2023. https://www.janssen.com/us-fda-approves-talveytm-talquetamab-tgvs-first-class-bispecific-therapy-treatment-patients-heavily