News|Articles|March 18, 2026
Varsetatug Masetecan Exhibits Early Efficacy, Safety in Late-Line Colorectal Cancer
Author(s)Andrea Eleazar, MHS
Fact checked by: Sabrina Serani
Listen
0:00 / 0:00
Key Takeaways
- Confirmed objective responses were observed at 8.6 and 10 mg/kg q3w, with a high overall disease control rate in late-line metastatic colorectal cancer.
- Progression-free survival estimates near 7 months suggest potentially durable benefit in a setting with limited effective options after multiple prior metastatic lines.
Phase 1 expansion shows Varseta-M delivers notable response rates and manageable safety in heavily pretreated metastatic colorectal cancer, with FDA registrational planning underway.
New dose-expansion data from the phase 1 CTMX-2051-101 study (NCT06265688) indicate encouraging efficacy and safety with the investigational antibody-drug conjugate (ADC) varsetatug masetecan (CX-2051; Varseta-M) in patients with late-line metastatic colorectal cancer (CRC).1
As of the data cut-off on January 16, 2026, there were 56 patients evaluable for efficacy at the expansion doses of 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg administered every 3 weeks, with the latter 2 dose levels prioritized for dose optimization. Notably, the confirmed overall response rate (ORR) was 20% at the 8.6-mg/kg dose level, whereas the ORR was 32% at the 10-mg/kg dose level. The disease control rate was 88% across the entire expansion cohort.
Furthermore, survival analysis showed an estimated progression-free survival (PFS) of 6.8 months (95% CI, 2.6-not estimable [NE]) at 8.6 mg/kg and 7.1 months (95% CI, 3.9-NE) at 10 mg/kg.
After evaluation of 93 total enrolled patients, the safety profile of Varseta-M was determined to be consistent with data presented from the dose-escalation phase. Most treatment-related adverse events were grade 1 or grade 2 in severity, with the most common event being diarrhea. Among those receiving the optimized doses and prophylactic regimens for diarrhea, the rate of grade 3 diarrhea was 10%.
“Patients with late-stage metastatic CRC face a poor prognosis and have very limited treatment options,” said Kimmie Ng, MD, MPH, associate chief of the Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute, in a news release.1“These exciting clinical data demonstrate that Varseta-M can drive consistent and durable responses with a manageable tolerability profile in patients with heavily pretreated CRC, supporting its promise as a potential new treatment option for advanced CRC.”
Mechanistic Rationale: The PROBODY Platform
Varseta-M is an EpCAM PROBODY® ADC consisting of an EpCAM-directed monoclonal antibody masked with a peptide that prevents binding to healthy tissue. EpCAM is highly expressed across several epithelial malignancies, including colorectal, gastric, and ovarian cancers.
While an attractive target, EpCAM’s expression on normal epithelial tissues has traditionally led to dose-limiting toxicities in clinical trials involving standard ADCs. Varseta-M utilizes the PROBODY® platform to address this therapeutic challenge. Once the mask is removed, the antibody binds to the tumor cell, is internalized, and releases its cytotoxic payload: masetecan, a potent topoisomerase-1 inhibitor. This conditional activation is intended to minimize systemic off-tumor toxicity while maximizing on-target efficacy.
Phase 1 Trial Design
The ongoing phase 1 study, initiated in 2024, is a first-in-human study designed to assess the safety, tolerability, and preliminary antitumor activity of Varseta-M monotherapy in adult patients with advanced solid tumors.2 The study consists of dose-escalation and -expansion portions in indication-specific patient cohorts.
The study is currently active at 4 sites in the US and is recruiting an estimated total enrollment of 160 patients. Patients are eligible for enrollment if they have a metastatic or locally advanced solid tumor that has progressed after standard therapy. Those currently enrolled in the study have received a median of 3 prior lines of therapy in the metastatic setting.
Next Steps in Development
Based on the positive interim data from phase 1, the sponsor plans to meet with the FDA in mid-year 2026 to discuss a potential registrational study design for Varseta-M monotherapy in advanced CRC.
A phase 1 study is underway to characterize the agent’s efficacy and safety in combination with bevacizumab (Avastin). A phase 1b/2 study slated for the end of 2026 will also investigate Varseta-M in combination with bevacizumab and chemotherapy.
REFERENCES
1. CytomX’s varsetatug masetecan (EpCAM PROBODY® ADC) continues to demonstrate positive data supporting potential as a new treatment option in late-line colorectal cancer. News release. CytomX Therapeutics. March 16, 2026. Accessed March 16, 2026. https://tinyurl.com/mtxhy6t7
2. First in human study of CX-2051 in advanced solid tumors. ClinicalTrials.gov. Updated February 20, 2026. Accessed March 16, 2026. https://clinicaltrials.gov/study/NCT06265688
Related Content
Advertisement
