Phase 2 Trial Begins Dosing of Cemsidomide Combo in R/R Multiple Myeloma

Investigators of the phase 2 MOMENTUM trial (NCT07284758) assessing cemsidomide plus dexamethasone in relapsed/refractory multiple myeloma have initiated dosing for the first patient, according to a press release from the developer, C4 Therapeutics.¹

The open-label, single-arm, multicenter study is investigating the anti-myeloma activity, safety, tolerability, pharmacokinetics, and pharmacodynamics of cemsidomide in combination with dexamethasone as treatment in the fourth line or later among those with relapsed/refractory disease. Approximately 100 patients will be assigned to receive cemsidomide at 100 µg for 14 days on and 14 days off as part of each treatment cycle.

“Initiating the phase 2 MOMENTUM trial, which builds upon the compelling anti-myeloma activity and differentiated safety profile established in the phase 1 trial, is a critical step for cemsidomide to become a foundational therapy for [patients with] multiple myeloma, who are in need of a safe, oral, and convenient treatment option,” Len Reyno, chief medical officer at C4 Therapeutics, stated in the press release.¹ “With this milestone accomplished, we are also on track to initiate the phase 1b trial of cemsidomide in combination with elranatamab-bcmm [Elrexfio] in the second quarter [of 2026], as we continue to advance our regulatory strategy that could deliver 2 accelerated approval paths in multiple myeloma.”

Developers engineered cemsidomide as an orally bioavailable molecular glue degrader of IKZF1/3, which are transcriptional factors associated with multiple myeloma biology. According to the press release, previous phase 1 data have demonstrated the agent’s differentiated safety and tolerability profile as well as its potential for yielding enduring outcomes.

The primary end point of the phase 2 MOMENTUM trial is overall response rate (ORR) per independent review committee assessment using International Myeloma Working Group (IMWG) criteria.² Secondary end points include duration of response, complete response rate, time to response, progression-free survival, overall survival, and adverse effects (AEs).

Patients 18 years and older with at least 3 prior lines of anti-myeloma therapy including an immunomodulatory drug, a proteasome inhibitor, an anti-CD38 antibody, and a T-cell engager or CAR T-cell therapy, were eligible for enrollment on the trial. Other eligibility criteria include having adequate organ function and refraining from donating blood during study treatment.

Those with presence of myeloma in the central nervous system or clinically significant impaired cardiac function or cardiac disease were ineligible for enrollment on the trial. Patients were also unsuitable for study entry if they had a thromboembolic event within 3 months of enrollment or uncontrolled active bacterial, fungal, or viral infection.

Investigators anticipate completing enrollment for the phase 2 MOMENTUM trial in the first quarter of 2027. The MOMENTUM trial is one component of a broader development strategy for cemsidomide, which includes a phase 1b study (NCT07280013) evaluating the agent in combination with elranatamab among patients with relapsed/refractory multiple myeloma.

The phase 1b trial is assessing cemsidomide, beginning at 75 µg, but potentially exploring 50 µg and 100 µg, in patients who have received 1 to 4 prior lines of treatment, including at least 1 IKZF1/3 degrader. The trial’s primary end points include the safety and tolerability of cemsidomide plus elranatamab based on dose-limiting toxicities and frequency and severity of AEs.³ Secondary end points include ORR, pharmacokinetics, and immunogenicity.

Patients 18 years and older with measurable disease per IMWG criteria and an ECOG performance status of 0 to 2 are eligible for enrollment on the phase 1b trial. Those with smoldering multiple myeloma, POEMS Syndrome, systemic light chain amyloidosis, or myelodysplastic syndrome are ineligible for study entry.

References

1. C4 Therapeutics announces first patient dosed in phase 2 MOMENTUM trial of cemsidomide, an oral IKZF1/3 degrader, in combination with dexamethasone for relapsed/refractory multiple myeloma. News release. C4 Therapeutics. February 23, 2026. Accessed February 23, 2026. https://tinyurl.com/2s3bmy4w
2. A study to evaluate the efficacy of cemsidomide + dexamethasone in participants with relapsed/​refractory multiple myeloma (MOMENTUM). ClinicalTrials.gov. Updated January 15, 2026. Accessed February 23, 2026. https://tinyurl.com/38xmpdn2
3. A study to learn about the effects of cemsidomide in combination with elranatamab in relapsed/​refractory multiple myeloma subjects. ClinicalTrials.gov. Updated January 29, 2026. Accessed February 23, 2026. https://tinyurl.com/bddnxyzr