FDA Approves Talquetamab for Relapsed/Refractory Multiple Myeloma

News
Article

The FDA has granted accelerated approval to talquetamab-tgvs 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.

FDA

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

Related Videos
Hans C. Lee, MD
Ariel Grajales-Cruz, MD
Rahul Banerjee, MD, FACP, assistant professor, Clinical Research Division, Fred Hutchinson Cancer Center; assistant professor, Division of Hematology and Oncology, University of Washington
Jeffrey Zonder, MD
A panel of 5 experts on multiple myeloma
A panel of 5 experts on multiple myeloma
Rachid Baz, MD, section head, Myeloma, Department of Malignant Hematology, Moffitt Cancer Center; co-director, Pentecost Family Myeloma Research Center
Joseph Mikhael, MD, professor, Applied Cancer Research and Drug Discovery Division, Translational Genomics Research Institute, City of Hope, chief medical officer, International Myeloma Foundation
Ricardo D. Parrondo, MD
Jeffrey Zonder, MD