Higher Doses of Subcutaneous Elranatamab Show Efficacy in Relapsed/Refractory Myeloma

Treating patients with relapsed/refractory multiple myeloma with subcutaneous elranatamab (PF-06863135), a BCMA-targeting humanized bispecific monoclonal antibody, was efficacious in higher doses, according to findings from a phase 1 clinical trial (NCT03269136) presented at the 2021 ASCO Annual Meeting.

“We recently reported on the intravenous dosing of elranatamab and demonstrated evidence of anti-myeloma activity in heavily pretreated relapsed/refractory multiple myeloma. We now extend these findings and report the results of subcutaneous elranatamab,” said Nizar J. Bahlis, MD, of the Arnie Charbonneau Cancer Institute at the University of Calgary, while reporting the findings.

“The primary objective was to assess the safety [and] tolerability of elranatamab administered, and determine recommended phase 2 doses. The secondary objectives include the evaluation of anti-myeloma activity, as well as the duration of response,” he added.

The trial tested weekly subcutaneous elranatamab in 30 patients across the following doses:

• 80 μg/kg (n = 6)
• 130 μg/kg (n = 4)
• 215 μg/kg (n = 4)
• 360 μg/kg (n = 4)
• 600 μg/kg (n = 6)
• 1000 μg/kg (n = 6)

On average, patients had received 8 prior treatments. The majority (87%) had triple-refractory disease, with nearly all patients (97%) having received prior anti-CD38 therapy. Twenty-three percent of patients received BCMA-directed antibody drug conjugate or chimeric antigen receptor (CAR) T-cell therapy.

Response was measured by IMWG criteria, and the data cutoff was February 4, 2021.

Doses at or above 215 μg/kg had the best outcomes, with an overall response rate (ORR) of 70% (n = 14). Out of the 215-, 360-, 600-, and 1000-μg/kg dose groups, the highest dose had the best outcomes, with an 83.3% ORR, including 16.7% of patients with a complete response, 50% with a very good complete response, and 16.7% with a partial response. Median time to response was 22 days, ranging from 21 to 50 days.

There were 14 patients with IMWG-confirmed response; in this cohort, median duration of response was not reached. There was a 92.3% probability (95% CI, 56.7-98.9) of responders being event-free at 6 months.

Within the entire study population, the most common all causality treatment-emergent adverse events (AEs) were lymphopenia (83.3%; grade 3, 20% and grade 4, 60%), cytokine release syndrome (CRS; 73%; all grade 1 and 2); anemia (57%; grade 3, 43% and grade 4, 3%); injection site reaction (53%; none above grade 2); thrombocytopenia (53%; grade 3, 23% and grade 4, 17%); and neutropenia (40%; grade 3, 17% and grade 4, 17%). There were no dose-limiting toxicities.

The researchers also found that body weight or baseline soluble BCMA were not a significant variant on total exposure, “therefore, this supports a fixed-dosing approach,” Bahlis said.

Ultimately, he added, that these findings should lead to future studies of elranatamab alone and in combination with other drugs.

“These results clearly support the further development of elranatamab, both as monotherapy or in combination with other anti-myeloma agents,” he said.

Reference

Bahlis NJ, Raje NS, Costello C, et al. Efficacy and safety of elranatamab (PF-06863135), a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MM). Presented at: 2021 ASCO Annual Meeting. June 4-8, 2021. Virtual. Abstract 8006.