A phase I monotherapy study assessing the safety and efficacy of GR1803, a BCMA×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma

Abstract

Abstract Background: Outcomes remain poor for patients with relapsed or refractory Multiple Myeloma (RRMM). GR1803 is a BCMA x CD3 bispecific antibody that redirects cytotoxic T cells to BCMA expressing myeloma cells. We report here the initial findings of Part 2 (Dose expansion stage) of the Phase I clinical study of GR1803 administered intravenously in patients with RRMM. Aims: The objective for Part 2 (Dose expansion stage) of the phase 1 study is to assess the efficacy, safety, tolerability, pharmacokinetics (PK), and immunogenicity of GR1803 in RRMM patients. Methods: Adult myeloma patients that relapsed after or were refractory to prior therapies, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody received GR1803 weekly by intravenous injection from week 1 to week 24, bi-weekly from week 24 to week 36, tri-weekly from week 36 to week 52. Patients had measurable disease per the International Myeloma Working Group (IMWG) criteria (2016). The Phase I study is divided into 2 parts: Dose Escalation (Part 1) and Expansion (Part 2). Part 2 (Dose expansion stage) enrolled a total of 3 dose cohorts, including 180 μg/kg without priming dose (n=23), 180 μg/kg with priming dose (n=25) and 240 μg/kg without priming dose (n=12) levels. Results: As of July 1, 2025, Part 2 has enrolled 60 subjects, 48 subjects receiving 180 μg/kg dosage (RP2D). Among RP2D group, 48 (100%) subjects experienced at least one treatment emergent adverse event (TEAE) and 47 (97.9%) subjects had a TEAE grade ≥ 3. Most frequently reported (≥ 5%) grade 3, 4 or 5 TEAEs include hypokalaemia 77.1% (20.9% Gr ≥ 3), cytokine release syndrome 89.6% (6.3% Gr ≥ 3), neutrophil count decreased 87.5% (75.0% Gr ≥ 3), white blood cell count decreased 87.5% (41.7% Gr ≥ 3), platelet count decreased 81.3% (41.7% Gr ≥ 3), aspartate aminotransferase increased 45.8% (6.3% Gr ≥ 3), lymphocyte count decreased 62.5% (60.4% Gr ≥ 3), upper respiratory tract infection 35.4% (6.3% Gr ≥ 3), pneumonia 64.6% (50.0% Gr ≥ 3), diarrhea 58.3% (12.5% Gr ≥ 3), anaemia 72.9% (31.3% Gr ≥ 3). 57 patients had at least one post-baseline efficacy assessment. The overall response rate (ORR) for the 57 evaluable subjects was 89.5% (51/57). The 180μg/kg dose (with or without priming dose) cohort enrolled a total of 48 subjects, with an ORR of 87.5% (42/48), an incidence of VGPR or better of 70.8% (34/48), an incidence of CR or better of 37.5% (18/48) and an incidence of MRD negative rate of 54.2% (26/48). Due to the high rate (50.0%) of patients with extramedullary multiple myeloma (EMM), median time to response (TTR) was 2.1 months. In patients without EMM, median TTR was 0.75 months. Median DOR was not reached. The probability of responders remaining in response at 9 months was 78.8% (95%CI: 60.3% to 89.4%). With a substantial follow-up in responders (median follow-up time: 12.4 month), a majority of responders maintained response and many subjects deepened response over time, suggesting a robust and durable effect. Among 48 patients who received 180μg/kg dose injection, 24 patients (50.0%) had EMM at baseline. The ORR was 83.3% (20/24), with 4 CR or sCRs, 9 VGPRs and 7 PRs. Conclusion: Treatment with GR1803 was well tolerated with excellent anti-myeloma activity, especially in patients with EMM. GR1803 is expected to improve the prognosis of patients with RRMM. Acknowledgments: This study was funded by Chongqing Genrix Biopharmaceutical Co., Ltd.