(OA-14) Cevostamab Plus Pomalidomide (Pom) and Dexamethasone (dex) in Relapsed/Refractory Multiple Myeloma (RRMM): Phase I Dose-Expansion Results from the CAMMA 1 Study

Introduction: Cevostamab, a FcRH5xCD3 T-cell-engaging bispecific antibody, has shown encouraging activity and manageable safety as monotherapy in patients (pts) with late-line RRMM (Richter et al. ASH 2024). Combining cevostamab with anti-myeloma agents that augment T-cell activity could enhance efficacy. In the Arm B safety run-in of the Phase Ib CAMMA 1 study (NCT03275103), cevostamab plus Pom and dex induced deep and durable responses and had manageable safety in pts with RRMM (Spencer et al. COMY 2025). We present initial data from the Arm B1E randomized dose expansion.

Methods: Eligible pts had RRMM and had received ≥1 prior immunomodulatory drug and ≥1 prior proteasome inhibitor as part of ≥1 prior line. Pts were randomized (1:1) to 70mg (low-dose [LD]) or 105mg (high-dose [HD]) cevostamab given Q2W in Cycles (C) 1–6 (28-day cycle) and Q4W in C7+, which was initiated after a pre-phase with 0.3/3.3mg double step-up dosing. From C1+, Pom (2mg) was given on Day (D) 1–21 and dex (20mg) on D1, 8, 15 and 22. Treatment was continued until disease progression (PD) or unacceptable toxicity.

Results:

At cut-off (January 22, 2025), 32 pts (n=16 in LD and n=16 in HD cohorts) were randomized and treated. Among those, 8.3% and 25.0% had a conclusive assay result for high-risk cytogenetics (t(4;14), t(14;16) or del(17p)), and 18.8% and 25.0% had extramedullary disease, respectively. Median number of prior lines was 2 and 3. One and 3 pts in the LD and HD cohorts had received ≥1 prior BCMA-targeted therapy. Triple-class refractory disease was present in 25.0% and 31.3%, and 68.8% in both cohorts were refractory to their last line.

Median follow-up was 8.9 and 7.5 months in the LD and HD cohorts, respectively. Objective response rates were 93.8% and 62.5% and very good partial response or better rates were 81.3% and 62.5%. At cut-off, 13/15 (86.7%) and 9/10 (90.0%) responders were still in response, with responses deepening over time.

Grade (Gr) 3–4 adverse events (AEs) occurred in 68.8% and 87.5% of LD and HD pts, respectively. Gr 3–4 AEs in ≥20% were neutropenia (56.3%; 62.5%), anemia (31.3%; 12.5%), thrombocytopenia (12.5%; 37.5%), and infections (12.5%; 25.0%). Cytokine release syndrome occurred in 13 pts (81.3%) in each cohort (LD: Gr 1, 56.3%; Gr 2, 18.8%; Gr 3, 6.3%; HD: Gr 1, 56.3%; Gr 2: 25.0%). Rash occurred in 4 (25.0%) and 9 (56.3%) pts; all events were Gr 1–2. Gr 5 (fatal) AEs excluding PD occurred in 2 pts (LD: cardiac arrest in a patient with pre-existing risk factors; HD: parainfluenzae pneumonia); both AEs were considered unrelated to treatment.

Conclusions: Cevostamab plus Pom and dex induces deep responses and has manageable safety in RRMM. Updated data from the Arm B dose expansion will be presented, including initial data from 32 additional pts in Arm B3E who received triple step-up dosing, and emerging biomarker analyses, including minimal residual disease, which will confirm the pattern of response and AEs with the LD and HD regimens.