CytomX Reports Positive Phase 1 Study Data for CX-2051 in Advanced Colorectal Cancer

CytomX Therapeutics, Inc., based in South San Francisco, recently announced promising interim results from its Phase 1 trial evaluating CX-2051, a novel therapeutic agent for advanced, late-line colorectal cancer (CRC). The study, known as CTMX-2051-101, is focused on assessing the efficacy of CX-2051, a masked, conditionally activated antibody-drug conjugate (ADC) targeting the epithelial cell adhesion molecule (EpCAM). As of the April 7, 2025 data cutoff, the trial showed significant potential in both efficacy and safety, providing new hope in the fight against a notoriously challenging cancer.

EpCAM, a target expressed in various cancers, has historically been difficult to drug due to its presence in normal tissues. However, CytomX's innovative approach has shown that CX-2051 could lead to improved treatment outcomes for CRC patients. CEO Sean McCarthy highlighted the breakthrough nature of these findings, noting that CX-2051 demonstrated impressive, durable anti-tumor activity in late-line metastatic CRC. This marks a significant advancement in addressing a high unmet need within the oncology community.

The Phase 1 trial, initiated in April 2024, included dose escalation across seven levels. By April 2025, 25 patients with advanced metastatic CRC had been treated with CX-2051 at various dose levels. Of these, 18 patients were eligible for efficacy evaluation after receiving at least one post-baseline tumor assessment. Notably, 28% of these patients exhibited confirmed partial responses according to RECIST v1.1 criteria, a significant improvement compared to currently approved third-line CRC therapies that typically show low single-digit response rates. Specifically, at the highest dose of 10 mg/kg, 43% of evaluable patients achieved partial responses, demonstrating the compound's promising efficacy.

The trial also reported a median progression-free survival of 5.8 months, with over half of the patients still undergoing treatment at the time of data cutoff. Safety assessments revealed that CX-2051 was generally well-tolerated with no dose-limiting toxicities observed. Most adverse events were of low severity, with diarrhea, nausea, vomiting, and fatigue being the most commonly reported. No severe adverse events were noted, underscoring the manageable safety profile of CX-2051.

As the study progresses, CytomX is initiating dose expansions at 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg to further refine the optimal dose for future trials. This expansion aims to enroll 20 patients at each dose level to better inform the Phase 2 recommendations. Anticipated milestones include a comprehensive Phase 1 data update by early 2026 and the launch of a Phase 2 study within the first half of that year. Additionally, CytomX is considering the initiation of combination studies with CX-2051 in earlier lines of CRC treatment and exploring its potential application in other EpCAM-expressing tumors.

CytomX Therapeutics continues to pioneer the development of conditionally activated biologics through its PROBODY® therapeutic platform. By focusing on localized treatments within the tumor microenvironment, the company seeks to create safer and more effective cancer therapies. With strategic collaborations in place with industry leaders such as Amgen and Bristol Myers Squibb, CytomX is well-positioned to advance its clinical pipeline and redefine the standard-of-care in oncology.