CytomX Advances Masked ADC Varsetatug Masetecan Toward Registrational Trial in Colorectal Cancer
Key Insights
CytomX Therapeutics announced key 2026 milestones for varsetatug masetecan (search), a masked antibody-drug conjugate targeting EpCAM (search) in colorectal cancer (search) patients.
The company plans to release Phase 1 expansion data in Q1 2026 from approximately 100 patients and initiate a combination study with bevacizumab.
CytomX aims to align with FDA on registrational study design for the potential first-in-class ADC in advanced colorectal cancer (search).
CytomX Therapeutics announced significant clinical development milestones for 2026, positioning its lead candidate varsetatug masetecan (search) (Varseta-M) for potential registrational studies in advanced colorectal cancer (search). The masked antibody-drug conjugate represents a novel approach to targeting EpCAM (search), a previously undruggable tumor antigen due to its expression on normal tissues.
Varseta-M Advances Toward Registration-Enabling Studies
The company is conducting Phase 1 dose expansions across three dose levels - 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg - administered every three weeks, with enrollment projected to reach approximately 100 patients by the planned Q1 2026 data update. CytomX aims to select optimal dosing for a potential registrational study in advanced colorectal cancer (search) based on these expansion results.
"We are excited to build on our transformational progress at CytomX with Varseta-M and will be focused on advancing this novel, potential first-in-class ADC towards a registrational study in late-line CRC," said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX. "Varseta-M was specifically designed to address a broad, unselected CRC patient population based on the universally high and uniform expression of EpCAM (search)."
The company plans to align with the FDA in 2026 on potential registrational study design for Varseta-M monotherapy in advanced colorectal cancer (search). Additionally, a Phase 1 combination study with bevacizumab is expected to start in Q1 2026, with initial data anticipated by the first half of 2027 to inform potential late-phase development in earlier lines of treatment.
Expanding Into Additional Indications
CytomX plans to initiate Phase 1 expansion cohorts in additional indications during the second half of 2026, leveraging EpCAM (search)'s broad expression across solid tumors. The masked ADC design aims to create a therapeutic window for this high-potential target while delivering meaningful anti-cancer activity.
Varseta-M was discovered in collaboration with ImmunoGen, now part of AbbVie (search), and features a topoisomerase-1 (search) inhibitor payload. The PROBODY therapeutic platform enables conditional activation specifically in the tumor microenvironment, potentially reducing systemic toxicity associated with traditional ADCs.
CX-801 Combination Data Expected
The company's second clinical-stage asset, CX-801, a masked interferon alpha-2b PROBODY cytokine, continues dose escalation in advanced melanoma (search). CX-801 monotherapy has reached the fourth dose level and demonstrated tolerability at doses exceeding the approved dose of unmasked interferon alpha-2b.
Phase 1 dose escalation of CX-801 in combination with pembrolizumab (KEYTRUDA) was initiated in May 2025 and is currently enrolling the second dose level. Initial clinical data for this combination in advanced melanoma (search) is anticipated by the end of 2026.
CX-801 monotherapy biomarker data presented at the 2025 Society of Immunotherapy of Cancer Annual Meeting supported the drug's mechanism of action and the rationale for the ongoing combination study with pembrolizumab.
Platform Technology and Strategic Positioning
CytomX's PROBODY therapeutic platform enables the development of masked, conditionally activated biologics designed for localized tumor microenvironment activity. The company's pipeline spans multiple treatment modalities including antibody-drug conjugates, T-cell engagers, and immune modulators such as cytokines.
The company has established strategic collaborations with multiple oncology leaders, including Amgen, Astellas, Bristol Myers Squibb, Regeneron and Moderna, supporting its platform development and clinical advancement strategies.