Talquetamab has received accelerated approval for patients with relapsed or refractory multiple myeloma.
The FDA has granted accelerated approval to talquetamab-tgvs (Talvey), a bispecific antibody therapy, to treat patients with relapsed or refractory multiple myeloma who have already received at least 4 lines of treatment, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.
The approval is supported by data from the phase 2 MonumenTAL-1 study (NCT04634552), in which the overall response rate (ORR) among 187 heavily pretreated patients was considered clinically meaningful. For patients who received a biweekly subcutaneous dose of 0.8 mg/kg, the ORR was 73.6% (95% CI, 63.0-82.4). At a median follow-up of nearly 6 months (range, 0-9.5), the very good partial response rate was 58% and the complete response rate was 33%.
For patients who received a weekly subcutaneous dose of 0.4 mg/kg, the ORR was 73.0% (95% CI, 63.2-81.4). At a median follow-up of nearly 14 months (range, 0.8-15.4), the very good partial response rate was 57% and the complete response rate was 35%.
The median duration of response was not estimated in the biweekly treatment group and 9.5 months in the 0.4 mg/kg weekly group. Moreover, among patients who received the 0.8 mg/kg biweekly dose, approximately 85% of responders maintained their 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, said in a press 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."
The MonumenTAL-1 study also included a cohort of 32 patients who had received prior treatment with a bispecific antibody or CAR T-cell therapy, as well as a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. These patients received weekly talquetamab at a dose of 0.4 mg/kg. The median follow-up time was 10.4, at which point 72% of patients experienced a response (95% CI, 53-86). Of note, approximately 59% of responses continued to experience their response for at least 9 months.
The prescribing label for talquetamab comes with a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome. Because of this, the newly approved agent is only available through the Tecvayli and Talvey Risk Evaluation and Mitigation Strategy (REMS).
The most common adverse events (AEs) to emerge in the trial were pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decrease, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. The most common grade 3 or 4 laboratory abnormalities were decreases in lymphocyte counts and neutrophil counts, white blood cell counts, and hemoglobin.
Oral toxicities occurred at a rate of 80%, and grade 3 oral toxicities were reported by 2.1% of patients. Dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%) were the most reported oral toxicities.
Moreover, 62% of patients lost weight while on treatment. Grade 2 weight loss was reported by 29% of patients and grade 3 weight loss occurred in 2.7% of patients. Sixty-two percent of patients experienced weight loss, including 29% with grade 2 weight loss and 2.7% with grade 3 weight loss.
Serious infections occurred in 16% of patients, with 1.5% of infections being fatal. Grade 3 or 4 infections occurred in 17% of patients. The rate of grade 3 and 4 decreased neutrophil counts was 35% and decreased platelet counts occurred in 22% patients. Further, skin reactions were reported by 62% of patients, and 0.3% of patients reported grade 3 skin reactions.
AEs caused 9% of patients on the trial to discontinue treatment.
"Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and, therefore, patients are in need of new treatment options," Michael Andreini, president and chief executive officer of the Multiple Myeloma Research Foundation, said in the release. "Today's approval of talquetamab provides patients with a new treatment approach for relapsed or refractory disease that is a welcome addition to the myeloma community."
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