CytomX reports promising Phase 1 expansion data for its EpCAM-targeting PROBODY ADC varsetatug masetecan (Varseta-M) in heavily pretreated metastatic colorectal cancer, showing up to 32% response rate and median PFS of 7.1 months in the CTMX-2051-101 trial.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
CytomX Therapeutics has reported encouraging Phase 1 expansion data for its EpCAM-targeting PROBODY® antibody-drug conjugate (ADC), varsetatug masetecan (Varseta-M), in patients with heavily pretreated metastatic colorectal cancer (CRC). The preliminary findings are based on data from the ongoing CTMX-2051-101 Phase 1 study (NCT06265688), with a cutoff date of January 16, 2026.
The data suggest that Varseta-M may offer a potential new treatment option for patients with advanced CRC who have limited therapeutic choices. CytomX noted that the results support further development of the therapy and discussions with the U.S. Food and Drug Administration regarding a potential registrational path.
In the Phase 1 study, a total of 93 patients with late-line metastatic CRC were enrolled across seven dose levels ranging from 2.4 mg/kg to 12 mg/kg. Sixty patients were treated in the expansion cohorts at doses of 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg, of whom 56 were evaluable for efficacy. Patients had received a median of three prior lines of therapy, with 96% previously treated with irinotecan. Liver metastases were present in 76% of patients, while 71% harbored KRAS mutations.
Among efficacy-evaluable patients treated at the expansion doses administered every three weeks, Varseta-M demonstrated promising clinical activity. At the 8.6 mg/kg dose, the confirmed overall response rate was 20% with an estimated median progression-free survival (PFS) of 6.8 months. At the 10 mg/kg dose, the confirmed response rate increased to 32% with an estimated median PFS of 7.1 months. Across the expansion dose range of 7.2 mg/kg to 10 mg/kg, the disease control rate reached 88%.
Dose optimization efforts are currently focused on the 8.6 mg/kg and 10 mg/kg doses using adjusted ideal body weight dosing and improved adverse-event management strategies. As of the data cutoff, 20 patients had been enrolled in this dose optimization phase toward a target enrollment of 40 patients.
Varseta-M showed a generally manageable safety profile consistent with earlier dose-escalation results. Most treatment-related adverse events were Grade 1 or Grade 2 in severity. The most common adverse event was diarrhea, which was typically manageable and reversible. No cases of interstitial lung disease, febrile neutropenia, or pancreatitis were observed.
Among the 80 patients treated at expansion and optimization doses between 7.2 mg/kg and 10 mg/kg, frequently reported treatment-related adverse events included diarrhea, nausea, vomiting, fatigue, hypokalemia, and anemia. A single treatment-related Grade 5 acute kidney injury was previously reported in a patient with a complex medical history, including a solitary kidney.
To reduce gastrointestinal toxicity, CytomX introduced an updated prophylactic regimen consisting of anti-motility medications such as loperamide or diphenoxylate/atropine along with budesonide. Among 20 patients treated with the updated regimen at the optimized dose levels, Grade 3 diarrhea occurred in 10%.
Sean McCarthy, D.Phil., Chief Executive Officer and Chairman of CytomX Therapeutics, said the findings reinforce the potential of Varseta-M to improve the standard of care for patients with late-line colorectal cancer and support plans to engage with regulators on a registrational strategy. He added that the company aims to expand development into earlier treatment settings and other EpCAM-expressing cancers.
Dr. Kimmie Ng, Associate Chief of the Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute, noted that patients with advanced metastatic CRC face a poor prognosis and limited treatment options. She said the early data suggest Varseta-M could deliver durable responses with a manageable tolerability profile in heavily pretreated patients.
Looking ahead, CytomX plans to present additional efficacy and safety data from the Phase 1 study at medical conferences in 2026. The company also intends to initiate discussions with the FDA regarding a potential registrational study of Varseta-M monotherapy in advanced CRC.
In parallel, CytomX has started a Phase 1 study evaluating Varseta-M in combination with bevacizumab for colorectal cancer. A Phase 1b/2 trial combining Varseta-M with bevacizumab and chemotherapy is expected to begin by the end of 2026. The company also plans to expand clinical development into additional EpCAM-expressing cancers during the second half of 2026.
References
CytomX’s Varsetatug Masetecan (EpCAM PROBODY® ADC) Continues to Demonstrate Positive Data Supporting Potential as a New Treatment Option in Late-Line Colorectal Cancer, 16 March 2026, CytomX’s Varsetatug Masetecan (EpCAM PROBODY® ADC) Continues to Demonstrate Positive Data Supporting Potential as a New Treatment Option in Late-Line Colorectal Cancer | CytomX Therapeutics, Inc.
First In Human Study of CX-2051 in Advanced Solid Tumors, ClinicalTrials.gov ID NCT06265688, https://clinicaltrials.gov/study/NCT06265688
About the Writer
Samiksha Vikram Jadhav is a B.Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She has a keen interest in healthcare advancements, clinical research, medical writing, and emerging therapies. Her work focuses on presenting developments in the pharmaceutical and healthcare sectors through clear and accurate scientific communication.