Recent Outcomes of Phase 1 Study of Elranatamab for R/R MM Patients

Elranatamab (PF-06863135) is a bispecific molecule that targets B-cell maturation antigen (BCMA) on multiple myeloma (MM) and CD3 on T-cells to activate T-cell proliferation and redirect the immune response against MM. The Phase 1 MagnetisMM-1 study (NCT03269136) evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of elranatamab as monotherapy or in combination with immunomodulatory agents for patients with relapsed or refractory (R/R MM).

Following the patients’ informed consent, elranatamab was administered subcutaneously either once a week or every two weeks at doses ranging from 80 to 1000µg/kg. A subset of patients was given a single priming dose of 600µg/kg or 44mg equivalent, followed by the recommended Phase 2 dose of RP2D, 1000µg/kg or 76mg equivalent, one week later. The adverse events that emerged during treatment were evaluated using the Common Terminology Criteria for Adverse Events (v4.03), and cytokine release syndrome (CRS) was assessed based on the American Society for Transplantation and Cellular Therapy criteria. The researchers analyzed PK, cytokine, soluble BCMA levels, and lymphocyte subsets and evaluated response per IMWG criteria. MRD was also measured through next-gen sequencing with a sensitivity of 1×10-5 per IMWG standards.

As of November 1st, 2021, 55 patients were treated with elranatamab monotherapy at doses of ≥ 215µg/kg. The median age of patients was 64, ranging from 42 to 80. Among the patients, 27% were Black/African American or Asian, and 27% had high-risk cytogenetics at baseline. The median number of prior lines of therapy was 6, ranging from 2 to 15, with 91% of patients being triple-class refractory. A total of 22% of patients received initial BCMA-targeted treatment, and 56% had undergone a prior stem cell transplant.

The most common treatment-emergent adverse events (TEAEs) were cytokine release syndrome (CRS), neutropenia, anemia, injection site reaction, and lymphopenia. The incidence of CRS was 67% at the recommended phase 2 dose (RP2D), with a single priming dose and premedication, evenly split between grades 1 and 2, with no incidents more severe than grade 2. The pharmacokinetic exposure was dose-dependent, and elranatamab at a dose of 1000µg/kg administered every two weeks achieved the direction associated with an anti-myeloma activity.

Elranatamab spurred T-cell growth with a median response time of 36 days (7-73 days). Soluble BCMA levels are reduced with disease response. The overall response rate (ORR) was 64%, with a 95% confidence interval (CI) of 50-75%, with a median follow-up of 8.1 months, ranging from 0.3 to 21 months, and only comprising International Myeloma Working Group (IMWG) confirmed responses. A total of 31% of patients achieved a complete response or better. The study revealed that in patients with R/R MM, elranatamab generates long-lasting clinical and molecular responses and has a tolerable safety profile.

Source: https://library.ehaweb.org/eha/2022/eha2022-congress/357757/andrew.dalovisio.updated.results.from.the.ongoing.phase.1.study.of.elranatamab.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2233%2Aot_id%3D26843%2Amarker%3D1769%2Afeatured%3D17676

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03269136

Dalovisio, A.1,*; Bahlis, N.2; Raje, N.3; Costello, C.4; Dholaria, B.5; Solh, M.6; Levy, M.7; Tomasson, M.8; Dube, H.9; Damore, M.9; Jiang, S.10; Basu, C.10; Skoura, A.11; Chan, E.12; Trudel, S.13; Jakubowiak, A.14; Chu, M.15; Gasparetto, C.16; Sebag, M.17; Lesokhin, A.18. UPDATED RESULTS FROM THE ONGOING PHASE 1 STUDY OF ELRANATAMAB, A BCMA TARGETED T-CELL REDIRECTING IMMUNOTHERAPY, FOR PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA. DOI: 10.1097/01.HS9.0000846460.44039.3d