SC Cevostamab Highly Active in BCMA-Naive R/R Multiple Myeloma

Initial results from the phase 1b CAMMA 3 study (EUDRACT: 2021-002307-36) shared during the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition showed that subcutaneous (SC) cevostamab achieved clinically meaningful activity in patients with relapsed/refractory multiple myeloma.¹

Results were presented by Phoebe Joy Ho, MBBS, DPhil, of Royal Prince Alfred Hospital and University of Sydney. Cevostomab was found to have induced deep, durable antitumor responses at target doses of 120 mg or greater. Of 52 efficacy-evaluable patients, the overall response rate (ORR) was 38.8% (95% CI, 24.1%–53.4%) across all tested dose levels. Further, the agent demonstrated a stringent complete response (sCR) in 14.3% of patients, complete response (CR) in 6.1%, very good partial response (VGPR) in 10.2%, and partial response in 8.2%. The median duration of response (DOR) was 12.3 months (95% CI, 8.3–not estimable).

Notably, responses were particularly pronounced among those patients who were B-cell maturation antigen (BCMA) therapy-naive, achieving an ORR of 52.0% (95% CI, 30.4%–73.6%) vs 25.0% (95% CI, 5.6%–44.4%) among those who were BCMA-exposed (n = 26, each group). The median DOR was not reached (95% CI, 11.7-not evaluable [NE]) in BCMA-naive patients and 8.3 months (95% CI, 4.9-NE) in BCMA-exposed patients, suggesting greater durability of response in BCMA-naive patients.

When asked about the markedly lower ORR in BCMA-exposed patients during the following question-and-answer session, Ho noted that while there are no definitive data to confirm drivers of these differences, several considerations regarding response duration, prior lines of therapy, and treatment timing may be relevant and are the subject of ongoing investigation.

“We did look at the timing of treatment between the BCMA-targeting agent and cevostamab. And while we don’t have absolutely clear data, it would be fair to mention that those patients who received another bispecific therapy and then received cevostamab had a shorter duration,” Ho responded. “One could hypothesize whether there is evidence of perhaps T-cell exhaustion in those patients with a short duration as low as approximately 7 weeks, whereas [in] the other 2 categories of antibody-drug conjugates [ADCs] as well as [chimeric antigen receptor T-cell (CAR T) therapy], the durations were much longer, and I believe, are unlikely to have affected the results.”

Further, among the 12 patients who achieved sCR/CR, a majority (n = 8) exhibited minimal residual disease (MRD) negativity. The remaining 4 patients were either MRD-positive or had baseline calibration failure (n = 2 each).

Except for the observed low-grade injection site reactions (ISRs), the safety and efficacy figures were noted to be generally comparable with that of intravenously (IV) administered cevostamab monotherapy, supporting the potential of SC cevostamab to offer a more convenient treatment option for providers and patients and advancement in further studies.

“On the basis of these data showing a clinical[ly] active compound given in the [SC] route, cevostamab is the subject of an ongoing development program aiming to establish its efficacy and safety, either IV or [SC], when given alone or in combination with standard-of-care novel therapies,” Ho said.¹

Adverse Events

Adverse events (AEs) were mainly grades 1 or 2. The most common any-grade AEs observed in the total dose-escalation population (n = 58) included cytokine release syndrome (CRS; 69.0%), ISR (58.6%), neutropenia (31.0%), anemia (29.3%), pyrexia (25.9%), and rash (17.2%). CRS events were mostly low-grade and effectively managed with tocilizumab (Actemra), steroids, or both. ISR events were also mainly mild and low-grade and occurred early in the treatment course.

Treatment-related AEs led to cevostamab discontinuation in 3 patients. Fatal AEs occurred in 3 patients, although none were deemed related to the treatment.

“Overall, the majority of [AEs] were mild and cytopenias were generally reversible, while treatment-related [AEs] leading to discontinuation were infrequent,” Phoebe Joy Ho, MBBS, DPhil, of Royal Prince Alfred Hospital and University of Sydney, said during the presentation of results.¹

About CAMMA 3: Rationale and Methodology

Findings from a phase 1 study (NCT03275103) presented at the 66th ASH Annual Meeting previously demonstrated the efficacy and safety of IV cevostamab in heavily pretreated patients with relapsed/refractory multiple myeloma.² The CAMMA 3 study was motivated by the need to develop a more convenient formulation that could expand treatment access and utilization.

Accordingly, the objective of the study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of SC cevostamab in late-line relapsed/refractory multiple myeloma.

As of February 24, 2025, 58 patients were enrolled and received at least 1 dose of SC cevostamab. Patients were heavily pretreated, with a median of 5 prior lines of therapy (range, 2–11). Nearly half (48.3%) had received prior BCMA-targeted therapy, including CAR T (10.3%), ADCs (32.8%), and bispecific antibodies (8.6%).

Like the IV regimen, the CAMMA 3 treatment regimen was administered on a fixed-duration schedule. Patients received cevostamab via SC injection for 13 28-day cycles over approximately 12 months or until disease progression. In cycle 1, patients received stepped-up dosing on days 1 and 8, during which hospitalization was mandatory; the target dose, ranging between 40 and 300 mg, was then administered on day 15. Target doses were subsequently administered every 2 weeks for 5 more cycles, followed by every 4 weeks until cycle 13. Patients were premedicated with IV corticosteroids during the first 2 cycles, as well as acetaminophen and diphenhydramine for all cycles.

DISCLOSURES: Ho declared consulting roles with Gilead Sciences, Janssen Pharmaceuticals, and Pfizer; she also declared receiving research funding from Novartis and honoraria from GSK.

References

1. Ho, PJ. Subcutaneous cevostamab demonstrates manageable safety and clinically meaningful activity in relapsed/refractory multiple myeloma (RRMM): First results from the Phase Ib CAMMA 3 study. Presented at: 67^th American Society of Hematology Annual Meeting and Exposition; December 6–9, 2025; Orlando, Florida. Abstract 700.‌
2. Richter J, Thomas SK, Krishnan AY, et al. Cevostamab in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM): Updated results from an ongoing phase I study demonstrate clinically meaningful activity and manageable safety and inform the doses and regimen for combination studies. Blood. 2024;144(Supplement 1):1021-1021. doi:10.1182/blood-2024-199542