C4T Advances Oral Myeloma Drug Cemsidomide into Key Phase 2 Trial

WATERTOWN, Mass. – February 23, 2026 – C4 Therapeutics (Nasdaq: CCCC) announced today that it has dosed the first patient in its Phase 2 MOMENTUM trial, a significant step forward for its investigational oral drug, cemsidomide. The study evaluates the therapy in combination with dexamethasone for patients with relapsed/refractory multiple myeloma (RRMM), a persistent and challenging blood cancer.

The initiation of this pivotal trial marks a critical milestone for a drug that aims to provide a safe, convenient, and effective oral treatment for a patient population with dwindling options. Cemsidomide belongs to a novel class of medicines known as targeted protein degraders, which represent a new frontier in oncology.

“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 multiple myeloma patients, who are in need of a safe, oral, and convenient treatment option,” said Len Reyno, chief medical officer of C4 Therapeutics.

A New Mechanism for a Persistent Cancer

Multiple myeloma, a cancer of plasma cells, is the second most common hematologic malignancy. Despite significant therapeutic advances over the past two decades, the disease remains incurable for most patients. A defining characteristic of myeloma is its pattern of remission and relapse, with patients often developing resistance to existing treatments over time, creating a profound and continuous unmet medical need.

Cemsidomide offers a novel approach to combat this. It is an orally bioavailable “molecular glue degrader” designed to destroy specific proteins that fuel the cancer’s growth. The drug targets IKZF1 and IKZF3, transcription factors known to be fundamental to the survival of multiple myeloma cells. By harnessing the body's own cellular machinery—the proteasome, or protein recycling system—cemsidomide effectively tags these cancer-driving proteins for elimination.

This mechanism, while sharing a target with older immunomodulatory drugs (IMiDs), is designed to be more precise. C4 Therapeutics has highlighted cemsidomide’s “differentiated safety and tolerability profile,” a key factor for patients who have undergone multiple rounds of taxing therapies. Data from the completed Phase 1 trial supports this claim, showing promising efficacy with manageable side effects. In that study, cemsidomide demonstrated an impressive 50% overall response rate (ORR) at the 100 µg dose level planned for Phase 2. Notably, one patient achieved a complete response that was also minimal residual disease (MRD)-negative, a deep level of response that is a strong predictor of long-term survival. The safety data was equally encouraging, with low rates of common hematologic toxicities like febrile neutropenia (5%) and severe thrombocytopenia (11%).

The MOMENTUM Trial and Its Strategic Importance

The Phase 2 MOMENTUM trial is an open-label, single-arm study that will enroll approximately 100 patients across multiple centers. It is designed to confirm the anti-myeloma activity of cemsidomide at the 100 µg dose, administered daily for 14 days followed by a 14-day rest period, in combination with weekly low-dose dexamethasone.

The trial’s patient population underscores the high bar cemsidomide aims to clear. Eligibility is restricted to patients with heavily pretreated RRMM who have received at least three prior lines of therapy. Crucially, these patients must have already been treated with the mainstays of modern myeloma care, including a proteasome inhibitor, an anti-CD38 antibody, a prior IKZF1/3 degrader, and an advanced T-cell redirecting therapy like a bispecific antibody or CAR-T. By targeting this post-CAR-T/bispecific population, C4 Therapeutics is testing cemsidomide in a setting where treatment options are exceptionally limited and resistance is common.

The primary goal of the study is to measure the overall response rate, which will be assessed by an independent review committee. The company anticipates completing enrollment for the trial in the first quarter of 2027, with further data analysis from the completed Phase 1 study expected in mid-2026.

A Two-Pronged Attack on Multiple Myeloma

The MOMENTUM trial is just one part of a broader, ambitious strategy for cemsidomide. C4 Therapeutics is simultaneously pursuing a second clinical path that could expand the drug’s use into earlier lines of treatment and in combination with other powerful agents. The company has announced its plan to initiate a Phase 1b trial in the second quarter of 2026 to evaluate cemsidomide in combination with elranatamab (ELREXFIO®).

Elranatamab is an FDA-approved bispecific antibody that works by binding to both the BCMA protein on myeloma cells and the CD3 receptor on T-cells, effectively directing the immune system to attack the cancer. The scientific rationale for combining these two drugs is compelling; they attack the cancer through complementary mechanisms. While cemsidomide directly triggers the destruction of proteins essential for the myeloma cell’s survival, elranatamab unleashes a T-cell-mediated assault. This combination has the potential for synergistic effects, possibly leading to deeper, more durable responses and overcoming resistance.

This second trial will enroll patients who have received one to four prior lines of therapy, a less heavily pretreated population than in the MOMENTUM study. This suggests C4 Therapeutics envisions cemsidomide not just as a last resort, but as a potential cornerstone of myeloma therapy that can be integrated with other treatments across the disease course.

Navigating a Competitive and Evolving Landscape

The field of multiple myeloma treatment is dynamic and increasingly crowded with innovative therapies. In recent years, the FDA has approved several potent T-cell engagers, including bispecific antibodies and CAR-T cell therapies, which have transformed outcomes for some patients. However, these treatments often require complex administration, hospitalization, and management of severe side effects like cytokine release syndrome.

Herein lies cemsidomide’s most significant potential advantage: its oral route of administration. For patients weary of frequent infusions and clinic visits, a safe and effective pill offers a substantial improvement in quality of life. If the MOMENTUM trial confirms the promising safety and efficacy profile seen in Phase 1, cemsidomide could become a highly attractive option for both physicians and patients.

C4 Therapeutics’ dual-track development strategy appears well-aligned with the current regulatory environment. The FDA has recently signaled increased openness to accelerated approval pathways for myeloma drugs based on surrogate endpoints like MRD negativity, an outcome cemsidomide has already produced. By pursuing two distinct clinical programs—one as a late-line oral therapy and another as an earlier-line combination agent—the company is maximizing its chances for success and potentially securing two separate paths to market. With a reported cash runway expected to last through the end of 2028, C4 Therapeutics appears well-funded to execute this strategy and bring this promising therapy closer to the patients who need it.