Background: Multiple myeloma (MM) remains an incurable disease. Although new treatment paradigms have increased survival, most patients relapse and treatment in later lines remains a challenge. Prognosis for patients refractory to immunomodulatory drugs, proteasome inhibitors and anti-CD38 antibodies is extremely poor, with an estimated survival of < 1 year (Gandhi et al. 2019). Therefore, patients with relapsed/refractory (R/R) disease represent a high unmet need, and new targets and treatment modalities are needed. Cevostamab is an IgG1-based T-cell-dependent bispecific antibody engineered to target the most membrane-proximal domain of fragment crystallizable receptor-like 5 (FcRH5) on myeloma cells, and cluster of differentiation 3 (CD3) on T cells. This dual binding results in efficient immunological synapse formation and T-cell-mediated killing of myeloma cells. In the ongoing first-in-human Phase I GO39775 study, intravenous (IV) administration of cevostamab monotherapy continues to show clinically meaningful activity and durable responses in patients with heavily pre-treated R/R MM (Trudel et al. ASH 2021), and uses Cycle (C) 1 step-up dosing for the mitigation of cytokine release syndrome (CRS). Subcutaneous (SC) delivery of antibody therapies has been shown to be effective and well tolerated and offers several advantages over IV administration in regards to improved healthcare utilization, including ease of administration, reduced treatment burden and reduced hospitalization. The slower absorption rate observed with SC versus IV antibody therapies may also support the potential for SC cevostamab to provide a further improved CRS profile (Bartlett et al. ASH 2021). CAMMA 3 (GO43227; ISRCTN26168155) is an open-label, multicenter, Phase Ib dose-escalation and dose-expansion trial evaluating the safety, tolerability, pharmacokinetics (PK) and preliminary activity of SC cevostamab monotherapy in patients with R/R MM. Methods: For inclusion, patients must be aged ≥18 years and must have R/R MM for which no established therapies are available or appropriate. Cevostamab is administered by SC injection in 28-day cycles, with step-up dosing in C1, q2w dosing in C2–6, and q4w dosing in C7–13. Patients may receive up to 13 cycles unless there is disease progression or unacceptable toxicity. Patients who respond to cevostamab but develop recurrent or progressive disease after 13 cycles may be eligible for cevostamab re-treatment. Primary objectives are to evaluate the safety and tolerability (including the maximum tolerated dose and dose-limiting toxicities) of SC cevostamab and to identify a recommended Phase II dose. Secondary objectives include assessment of PK, activity, and immunogenicity, and identification of biomarkers associated with response and resistance. Clinical trial information: 26168155.