PHASE 1/2 FIH STUDY OF REGN5458 (ANTI-BCMA X ANTI-CD3 BISPECIFIC ANTIBODY) IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 8
- 主要终点
- Phase 1: Incidence and severity of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
PHASE 1 • Part 1 (Intravenous Dose Escalation): To assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine one or more recommended phase 2 dose regimens (RP2DRs) of REGN5458 as intravenous (IV) monotherapy in patients with relapsed or refractory multiple myeloma (RRMM) • Part 2 (Subcutaneous Administration): To assess the safety, tolerability, and dose-limiting toxicities (DLTs), and pharmacokinetic (PK) properties, and to determine a dosing regimen of subcutaneous REGN5458 monotherapy in patients with RRMM. PHASE 2 • Cohorts 1 and 2: To assess the anti-tumor activity of IV REGN5458 separately in cohorts 1 and 2, as measured by objective response rate (ORR) and as determined by an Independent Review Committee (IRC), in patients who have progressed on or after 3 prior lines of therapy or who are triple-refractory (defined as refractory to a(n) proteasome inhibitor (PI), immunomodulatory imide drug (IMiD), and anti-CD38 monoclonal antibody). • Cohort 3: To assess the safety and efficacy of anti-IL-6R pre-treatment in preventing CRS in patients treated with IV REGN5458, and to assess anti-tumor activity in patients who receive anti-IL-6R pre-treatment as measured by investigator assessed ORR in patients who had previously progressed on or after 3 prior lines of therapy or who are triple-refractory (defined as refractory to a(n) PI, IMiD, and anti-CD38 monoclonal antibody), and in patients who had previously relapsed after receiving BCMA directed chimeric antigen receptor (CAR)-T cellular therapy.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria
- •Patients must have myeloma that is response-evaluable according to the 2016 IMWG response criteria as defined in the protocol.
- •Phase 1, Part 1 (Dose Escalation): Patients with MM who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease or intolerance of the therapy and including either: a. Progression on or after at least 3 lines of therapy, or intolerance of therapy, including a PI, an IMiD, and an anti-CD38 antibody, OR b. Progression on or after an anti-CD38 antibody and have disease that is "double refractory" to a proteasome inhibitor and an IMiD, or intolerance of therapy. The anti-CD38 antibody may have been administered alone or in combination with another agent such as a proteasome inhibitor (PI). Refractory disease is defined as lack of response or relapse within 60 days of last treatment.
- •Phase 1, Part 2 (SC Administration): Patients with MM whose disease meets the following criteria: a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple-refractory, defined as being refractory to prior treatment with at least 1 anti-CD38 antibody, a PI, and an IMiD.
- •Phase 2 (Cohorts 1 and 2): Patients with MM whose disease meets the following criteria: a. Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR b. Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody. *Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.
- •Phase 2 (Cohort 3): Patients with MM whose disease meets the following criteria: Progression on or after at least 3 prior lines of therapy including a(n) PI, IMiD, and anti-CD38 antibody, OR Patients must be triple- refractory, defined as being refractory* to prior treatment with at least 1 PI, 1 IMiD, and an anti-CD38 antibody. * Refractory disease is defined as progression during treatment or within 60 days after completion of therapy, or <25% response to therapy.
- •AND, if patients have relapsed after a BCMA-directed CAR-T cellular therapy then: • Treatment with a CAR-T must have been associated with a response of PR or better, and • If CAR-T cellular therapy was the most recent prior therapy, excluding corticosteroids, then treatment must have been a minimum of 60 days prior to treatment with REGN
- •Other protocol defined inclusion criteria apply
排除标准
- •Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis, (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Patients with known MM brain lesions or meningeal involvement
- •Cardiac ejection fraction <40% by echocardiogram or multi-gated acquisition scan (MUGA)
- •Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific antibodies and BiTEs. Note: BCMA antibody-drug conjugates are not excludedand BCMA-directed CAR-T treatment is not excluded in Phase 2 Cohort
- •History of allogeneic stem cell transplantation at any time, or autologous stem cell transplantation within 12 weeks of the start of study treatment
- •Other protocol defined exclusion criteria apply
结局指标
主要结局
Phase 1: Incidence and severity of treatment-emergent adverse events (TEAEs)
Phase 1: Incidence and severity of treatment-emergent adverse events (TEAEs)
Phase 1: Incidence and severity of adverse events of special interest (AESI)
Phase 1: Incidence and severity of adverse events of special interest (AESI)
Phase 2, cohorts 1 and 2: Objective response rate (ORR) as determined by an Independent Review Committee (IRC)
Phase 2, cohorts 1 and 2: Objective response rate (ORR) as determined by an Independent Review Committee (IRC)
Phase 2, cohort 3: Incidence and severity of cytokine release syndrome (CRS) with REGN5458
Phase 2, cohort 3: Incidence and severity of cytokine release syndrome (CRS) with REGN5458
Phase 2, cohort 3: ORR of IV REGN5458 as assessed by investigator
Phase 2, cohort 3: ORR of IV REGN5458 as assessed by investigator
次要结局
- Phase 1 and Phase 2: Titer of anti-drug antibodies (ADAs) to REGN5458 over time
- Phase 1 and Phase 2: Incidence of neutralizing antibodies (Nab) to REGN5458 over time
- Phase 2, cohorts 1 and 2: Duration of response (DOR) as determined by an IRC, measured using the IMWG criteria
- Phase 1 part 1 and Phase 2: Concentrations of REGN5458 in the serum over time
- Phase 1 and Phase 2: Incidence over time of anti-drug antibodies (ADAs) to REGN5458
- Phase 1 and Phase 2, cohorts 1 and 2: DOR as determined by an investigator, measured using the International Myeloma Working Group (IMWG) criteria
- Phase 2, cohorts 1 and 2: Progression-free survival (PFS) as determined by an IRC, measured using the IMWG criteria
- Phase 1 and Phase 2, cohorts 1 and 2: PFS as determined by an investigator, measured using the IMWG criteria
- Phase 1: Rate of minimal residual disease (MRD) negative status using the IMWG criteria
- Phase 2: Rate of MRD negative status
- Phase 1 and Phase 2: Overall survival (OS)
- Phase 1, part 1 dose level 7 (DL7): ORR as measured as determined by blinded IRC, as measured using the IMWG criteria
- Phase 1 and Phase 2, cohorts 1 and 2: ORR as determined by the investigator, measured using the IMWG criteria
- Phase 2: Effects of REGN5458 on health-related quality of life (HRQoL) and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
- Phase 2: Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])
- Phase 2: Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])
- Phase 2: Change in patient-reported global health status/QoL per EORTC QLQ-C30
- Phase 2: Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
- Phase 2: Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30
- Phase 2: Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20
- Phase 2: Incidence and severity of TEAEs with REGN5458
- Phase 2: Incidence and severity of AESIs with REGN5458
研究者
Medical Affairs
Scientific
Regeneron Pharmaceuticals Inc.