CytomX's Varsetatug Masetecan (Varseta-M) Receives FDA Fast Track Designation for Colorectal Cancer

FDA has granted fast track designation to varsetatug masetecan (Varseta-M), CytomX Therapeutics' investigational antibody-drug conjugate (ADC), for the treatment of relapsed/refractory metastatic colorectal cancer, the company announced August 27, 2026.¹ According to the company, Varseta-M is a potential first-in-class ADC directed toward epithelial cell adhesion molecule (EpCAM), armed with a topoisomerase-1 inhibitor payload.¹

"Varseta-M was intentionally designed for patients with colorectal cancer based on the high expression of EpCAM in this cancer type," said Sean McCarthy, DPhil, chairman and CEO of CytomX Therapeutics, in a company press release.¹ "Receiving [f]ast [t]rack [d]esignation is an important milestone for the program and reflects its potential to address a highly unmet medical need in patients with relapsed/refractory metastatic colorectal cancer where we continue to work towards a planned first registrational trial in the first half of 2027."

What clinical data support the designation?

Fast track designation follows earlier phase 1 data from the ongoing CTMX-2051-101 trial (NCT06265688).¹,² As of a January 16, 2026 data cutoff, 93 patients with late-line metastatic colorectal cancer had been enrolled, including 56 evaluable for efficacy in the expansion cohort. According to the company in a March 2026 announcement, Varseta-M produced a confirmed objective response rate of 32% at the 10 mg/kg dose and 20% at the 8.6 mg/kg dose, with an overall disease control rate of 88% across the expansion cohort.³ Estimated progression-free survival was 7.1 months at the 10 mg/kg dose and 6.8 months at 8.6 mg/kg.³ The most common treatment-related adverse event was diarrhea, with a grade 3 diarrhea rate of 10% among patients receiving optimized doses and prophylactic management.³

"Patients with late-stage metastatic CRC [colorectal cancer] 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 the March 2026 company announcement.³ "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."

How does Varseta-M work?

Varseta-M uses CytomX's PROBODY platform, in which the antibody is masked with a peptide that prevents binding to healthy tissue until it reaches the tumor microenvironment. Once activated, the antibody binds EpCAM-expressing tumor cells and releases its cytotoxic topoisomerase-1 inhibitor payload, masetecan.³ EpCAM is highly expressed in colorectal and other epithelial cancers but has historically been difficult to target directly because of its expression on normal tissue as well.¹

"You can have the same linker and payload, but having a better internalizing antibody is going to make the ADC much more effective and targeted to cancer cells," said Sabeen Mekan, MD, senior vice president and chief medical officer at Zymeworks, in a previous interview with BioPharm International® during the BIO International Convention in June 2026.⁴ Varseta-M was discovered in collaboration with ImmunoGen, now part of AbbVie.¹

What's next for Varseta-M?

CytomX plans to initiate a potential registrational monotherapy trial of Varseta-M in relapsed/refractory metastatic colorectal cancer in the first half of 2027.¹ The company is also studying Varseta-M in combination with bevacizumab and, separately, plans a phase 1b/2 study combining it with chemotherapy.³ Fast track designation is intended to facilitate development and expedite FDA review of therapies for serious conditions with unmet medical need.¹

What are the limitations?

Fast track designation does not necessarily guarantee eventual FDA approval. The efficacy data supporting this designation come from an interim, single-arm phase 1 analysis without a placebo or active comparator, and confirmatory data from a registrational trial have yet to be generated.

References

1. CytomX Therapeutics. CytomX Therapeutics announces FDA fast track designation for varsetatug masetecan ("Varseta-M") for relapsed/refractory metastatic colorectal cancer (R/R mCRC). Press release. Published August 27, 2026. Accessed August 27, 2026. https://ir.cytomx.com/news-releases/news-release-details/cytomx-therapeutics-announces-fda-fast-track-designation
2. ClinicalTrials.gov. First in human study of CX-2051 in advanced solid tumors. NCT06265688. Updated July 15, 2026. Accessed August 27, 2026. https://clinicaltrials.gov/study/NCT06265688
3. CytomX Therapeutics. CytomX's varsetatug masetecan (EpCAM PROBODY ADC) continues to demonstrate positive data supporting potential as a new treatment option in late-line colorectal cancer. Press release. Published March 16, 2026. Accessed August 27, 2026. https://ir.cytomx.com/news-releases/news-release-details/cytomxs-varsetatug-masetecan-epcam-probodyr-adc-continues
4. Schoenthaler E, Mekan S. Improving ADC tolerability could expand long-term cancer treatment options. BioPharm International. Published June 22, 2026. Accessed August 27, 2026. https://www.biopharminternational.com/view/bio-2026-improving-adc-tolerability-could-expand-long-term-cancer-treatment-options