FDA Grants Fast Track Designation to ADC Varseta-M for mCRC

The FDA has granted fast track designation to the antibody-drug conjugate (ADC) varsetatug masetecan (CX-2051; Varseta-M) for patients with relapsed/refractory metastatic colorectal cancer (R/R mCRC), a designation meant to speed the drug's development and regulatory review for a population with a high unmet need.¹

Varseta-M is a first-in-class ADC that pairs a monoclonal antibody against epithelial cell adhesion molecule (EpCAM) with a topoisomerase 1 inhibitor payload.

"Varseta-M was intentionally designed for patients with
colorectal cancer based on the high expression of EpCAM in this cancer type," Sean McCarthy, PhD, chairman and chief executive officer of CytomX Therapeutics, the developer of Varseta-M, stated in a press release. "Receiving fast track designation is an important milestone for the program and reflects its potential to address a highly unmet medical need inpatients with relapsed/refractory metastatic colorectal cancer where we continue to work towards a planned first registrational trial in the first half of 2027."¹

The fast track designation follows previously reported encouraging phas findings in R/R mCRC from the dose-expansion portion of the ongoing first-in-human study CTMX-2051-101. As of a January 2026 data cutoff, 93 patients with heavily pretreated CRC had enrolled, of whom 56 were evaluable for efficacy across 3 expansion dose levels of Varseta-M given once every 3 weeks. Objective response rate (ORR) rose with dose, from 6% (1 of 17 patients) at 7.2 mg/kg, to 20% (4 of 20 patients) at 8.6 mg/kg, to 32% (6 of 19 patients) at 10 mg/kg.

Median progression-free survival (PFS) followed a similar pattern, reaching 5.5 months, 6.8 months, and 7.1 months, respectively, across those same dose cohorts. Disease control rate (DCR) was consistently high regardless of dose, at 88% (15 of 17), 90% (18 of 20), and 84% (16 of 19), for an overall DCR of 88% (49 of 56) across the pooled expansion population.²

The study enrolled without prospective selection for EpCAM expression, and CytomX reported that all patients with evaluable tumor biopsies had high EpCAM expression by immunohistochemistry, consistent with the biological rationale for the target in colorectal cancer. The treated population was heavily pretreated, with a median of 3 prior lines of therapy in the metastatic setting, prior irinotecan exposure in 96% of patients, liver metastases in 76%, and KRAS-mutant tumors in 71%.²

Safety Profile Centered on Gastrointestinal Toxicity

Among the 93 patients evaluable for safety, including 80 treated across the 7.2 10 mg/kg expansion and optimization doses, the most frequently reported treatment-related adverse events (TRAEs) were gastrointestinal and constitutional in nature. Diarrhea affected 68 patients, with 19 cases graded 3 or higher; nausea affected 44 patients, with 4 cases grade 3; vomiting affected 29 patients, with 3 cases grade 3; and fatigue affected 32 patients, with 2 cases grade 3. Hypokalemia occurred in 21 patients, 13 of whom had grade 3 or higher events, and anemia occurred in 13 patients, 6 of whom had grade 3 events.

Serious treatment-related events reported in more than one patient included diarrhea in 4 patients, vomiting in 3, hypokalemia in 3, dehydration in 3, acute kidney injury in 2, and colitis in 2. One treatment-related grade 5 event occurred, an acute kidney injury in a patient with a solitary kidney that followed grade 3 nausea and grade 2 diarrhea; no other treatment-related deaths were reported, and the company noted no cases of interstitial lung disease, febrile neutropenia, or pancreatitis.²

CytomX introduced a prophylactic bowel regimen in the fourth quarter of 2025, combining an antimotility agent, either loperamide or diphenoxylate/atropine, with budesonide, and began dosing patients according to adjusted ideal body weight (AIBW). Among the 20 patients treated at the 8.6 mg/kg and 10 mg/kg doses under this updated approach, the rate of grade 3 diarrhea was 10%. The company described diarrhea as generally manageable and reversible.²

Trial Design and Next Steps

CTMX-2051-101 is the first-in-human study of Varseta-M, structured with an initial dose-escalation phase followed by dose-expansion cohorts in R/R mCRC that generated the efficacy and safety data described above. Beyond the monotherapy cohorts, CytomX has also opened a phase 1 combination study pairing Varseta-M with bevacizumab (Avastin) and expects to begin a phase 1b/2 combination study adding chemotherapy to that bevacizumab backbone before the end of 2026. The company additionally plans to open expansion cohorts evaluating Varseta-M in other EpCAM-expressing tumor types in the second half of 2026.²

References

1. CytomX Therapeutics, Inc. CytomX Therapeutics Announces FDA Fast Track
Designation for Varsetatug Masetecan ("Varseta-M") for
Relapsed/Refractory Metastatic Colorectal Cancer (R/R mCRC). News release.
August 27, 2026. Accessed August 27, 2026. https://tinyurl.com/4bzbprdx

2. CytomX Therapeutics, Inc. 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. March 16, Accessed August 27, 2026. https://tinyurl.com/mpj8dkjj