Phase 1b Trial Initiated for Cemsidomide/Elranatamab in R/R Myeloma

The first patient has been dosed in a phase 1b clinical trial evaluating cemsidomide combined with elranatamab (Elrexfio) for the treatment of relapsed/refractory multiple myeloma (R/R MM), according to a news release from C4 Therapeutics.¹

The combination pairs an investigational oral IKZF1/3 degrader with an FDA-approved B-cell maturation antigen (BCMA)–CD3 bispecific antibody, following favorable outcomes of a phase 1 trial of cemsidomide.²

Trial Design and End Points

The open-label, multicenter phase 1b study (NCT07280013) will enroll up to 54 patients across multiple dose cohorts. The trial begins at a cemsidomide dose of 75 µg, with plans to explore 50 µg and 100 µg dose levels simultaneously. Eligible patients must have received 1 to 4 prior lines of therapy, including at least 1 prior IKZF1/3 degrader, but must not have received prior BCMA-directed T-cell engager or chimeric antigen receptor T-cell (CAR-T) therapy.¹

The primary end point is safety and tolerability of the combination. Secondary end points include overall response rate (ORR) and minimal residual disease (MRD)-negative complete response rate per International Myeloma Working Group (IMWG) criteria, duration of response, minimal residual disease negativity, and other measures of anti-myeloma activity. Phase 1b data from all cohorts are anticipated in mid-2027.

The trial is sponsored and conducted by C4 Therapeutics; elranatamab is being provided by Pfizer at no cost under a clinical trial collaboration and supply agreement.

Rationale for the Combination

Bispecific T-cell engagers have rapidly become a cornerstone of R/R MM treatment. Cemsidomide is an orally bioavailable molecular glue degrader of IKZF1/3 that demonstrated robust T-cell activation and cytokine expression across multiple doses, suggesting the drug could amplify the anti-myeloma immune response when combined with a BCMAxCD3 bispecific such as elranatamab.

Len Reyno, MD, chief medical officer of C4 Therapeutics, stated in a news release that cemsidomide's “potent direct anti-myeloma effect and its ability to enhance the immune environment” may “deliver a deeper and more durable therapeutic response for patients, including those in earlier lines of therapy.”

Elranatamab combined with iberdomide, a cereblon E4 ligase modulatory drug that also targets IKZF1/3, showed favorable early outcomes in the phase 1b MagnetisMM-30 trial (NCT06215118).³

Cemsidomide Plus Dexamethasone

The phase 1b trial builds on a completed phase 1 first-in-human study of cemsidomide and dexamethasone in patients with R/R MM. Cemsidomide demonstrated a differentiated tolerability profile and promising efficacy signals across dose levels. In a heavily pretreated R/R MM population (n = 67), the ORR was 34% (n = 23/67) overall, with a clinical benefit rate of 49%. Activity was dose-dependent: at the highest dose level evaluated, 100 µg once daily (n = 14), the ORR reached 50%, with a clinical benefit rate of 64%. Deep responses were observed, including stringent complete responses, and MRD negativity was achieved in 1 patient with a complete response at the 100-µg dose.²

The regimen was well tolerated with only 1 discontinuation and 4 dose reductions related to adverse events. On the basis of these data, 100 µg was identified as the recommended phase 2 dose.

Broader Development Strategy

The phase 1b combination trial is 1 component of a broader program to position cemsidomide across multiple treatment lines. C4 Therapeutics is also conducting the phase 2 MOMENTUM trial (NCT07284758), a single-arm study evaluating cemsidomide plus dexamethasone in patients with R/R MM who have received at least 3 prior regimens, including an IKZF1/3 degrader, a proteasome inhibitor, an anti-CD38 antibody, and a T-cell engager or chimeric antigen receptor T-cell therapy. The primary end point of MOMENTUM is ORR per IMWG criteria assessed by independent review committee, with enrollment of approximately 100 patients planned.¹

C4 Therapeutics has indicated it intends to evaluate cemsidomide with additional anti-myeloma agents and plans to disclose those combination strategies in mid-2026.

REFERENCES

1. C4 Therapeutics Announces First Patient Dosed in Phase 1b Trial of Cemsidomide in Combination with Elranatamab (ELREXFIO®) for Relapsed/Refractory Multiple Myeloma. News release. C4 Therapeutics. March 25, 2026. Accessed March 26, 2026. https://tinyurl.com/2rdpu5xa

2. Dhakal B, Yee AJ, Richardson PG, et al. Updated results of a phase 1 first-in-human study of cemsidomide (CFT7455), a novel MonoDAC® degrader, with dexamethasone in patients with relapsed/refractory multiple myeloma. Presented at: 22nd Annual Myeloma Society Meeting; September 17–20, 2025; Toronto, Canada.

3. Suvannasankha A, Kaufman JL, Badros A, et al. Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: results from the phase 1b MagentisMM-30 trial. Presented at: 2025 ASH Annual Meeting; December 6-9, 2025; Orlando, FL. Abstract #100.