CytomX Therapeutics (NASDAQ:CTMX) outlined updated Phase 1 dose expansion results for its EpCAM-targeting Probody antibody-drug conjugate (ADC) varsetatug masetecan (Varseta-M, “Varseta”) during a conference call covering 2025 financial results and new clinical data. Management emphasized that the call’s primary focus was Varseta’s late-line metastatic colorectal cancer (CRC) data and the company’s evolving strategy for dose selection and gastrointestinal adverse event management ahead of planned registrational studies.
Varseta-M’s design and rationale in colorectal cancer
Chief Executive Officer and Chairman Dr. Sean McCarthy said CytomX designed Varseta-M to “unlock” EpCAM as an ADC target in CRC, a tumor type he described as a major unmet need. He noted that EpCAM is highly expressed in CRC but also present on normal epithelial tissues, which has historically limited EpCAM-directed approaches due to toxicity. CytomX’s Probody platform uses a protease-dependent masking strategy intended to reduce binding in normal tissues and enable tumor-localized activation.
Phase 1 enrollment and patient population
Chief Medical Officer Dr. Wayne Chu reviewed the Phase 1 study population and updated enrollment. As of a January 16, 2026 data cutoff, 93 patients had been enrolled across dose escalation, expansion, and dose optimization cohorts, up from 73 patients previously reported in August. The efficacy update on the call focused on 60 patients treated at prioritized expansion doses of 7.2, 8.6, and 10 mg/kg administered every three weeks.
Chu characterized the enrolled population as representative of late-line metastatic CRC, noting that most patients had received at least three prior lines of therapy, nearly half had at least four prior lines, and more than one-quarter had received bevacizumab plus Lonsurf previously. Three-quarters had liver metastases at baseline, the majority had KRAS-mutated tumors, and most tumors were microsatellite stable, with only one patient known to have MSI-high disease.
Efficacy: response rates and progression-free survival
Across the expansion cohorts, CytomX reported confirmed objective response rates (per RECIST 1.1) of 20% at 8.6 mg/kg and 32% at 10 mg/kg. Chu said tumor reductions and disease control were observed across dose levels, including in patients with KRAS-mutated and KRAS wild-type tumors and in those with or without liver metastases.
Chu also said EpCAM expression measured by immunohistochemistry on baseline tumor biopsies remained uniformly high in evaluable tumors, with all having H-scores above 200 and the “vast majority” at or above 250 (with 300 described as the maximum).
On durability, Chu said median follow-up exceeded eight months, with 16 patients continuing on treatment at the time of the data cutoff and several treated for more than 11 months. Updated median progression-free survival (PFS) estimates were 7.1 months at 10 mg/kg and 6.8 months at 8.6 mg/kg. Management noted that PFS estimates could continue to mature, given follow-up time and censoring.
McCarthy added that CytomX’s preliminary PFS estimate had improved since a May 2025 disclosure, moving from 5.8 months to a range of 6.8 to 7.1 months.
Safety update: focus on diarrhea mitigation and dose optimization
Chu said no dose-limiting toxicities were observed in dose escalation. He highlighted that toxicities seen with other EpCAM-directed therapies—such as pancreatitis and severe liver toxicities—were not observed with Varseta-M, and interstitial lung disease seen with some other topoisomerase I ADCs was also not observed. He added that hematologic toxicity rates were “relatively low,” while diarrhea was the most common treatment-related adverse event and the primary safety focus.
During expansion, the company evaluated mitigation strategies for diarrhea. Chu said CytomX initially recommended loperamide prophylaxis for high-risk patients, but it was not widely used early in expansion due to physician practice patterns, patient preferences, and rapid enrollment. He also discussed experience with oral budesonide, stating that 12 of 14 patients who developed grade 2 or grade 3 diarrhea had at least a one-grade reduction in severity after starting budesonide.
Based on pharmacokinetic and exposure-response analyses, CytomX moved into dose optimization cohorts using:
- Adjusted ideal body weight (AIBW) dosing at 8.6 or 10 mg/kg to reduce interpatient variability
- Mandatory dual prophylaxis with loperamide and budesonide for all patients, regardless of baseline risk
In an analysis of treatment-related adverse events within the first two months of treatment, grade 3 diarrhea was reported in 29% of patients in the dose escalation/expansion set at 8.6 and 10 mg/kg, compared with 10% (2 of 20 patients) in early dose optimization cohorts. Chu said grade 3 hypokalemia, described as a known consequence of diarrhea-related fluid and electrolyte imbalance, similarly declined in the optimization group.
Across all cohorts and dose levels, CytomX reported treatment discontinuations due to related adverse events of 11%.
Pharmacokinetics, dose selection, and next steps toward registrational studies
Chu said pharmacokinetics in the escalation/expansion patients were dose proportional, with observed interpatient variability that the company aims to reduce using AIBW dosing. He said Varseta-M circulates primarily in masked form, has a mean half-life of 6 to 8 days, and unconjugated Cam59 levels in circulation were low at approximately 1% to 3% of total Varseta-M.
Chu also described an exposure-response model using a six-month PFS landmark metric, stating that exposure levels with AIBW dosing at 8.6 and 10 mg/kg fell within the exposure range observed in expansion cohorts and were predicted to deliver similar efficacy to non-optimized dosing.
On the call’s Q&A, McCarthy said CytomX was still working on the size of its first pivotal trial and was evaluating a potential third-line setting, while noting overall survival (OS) would be important and that the company plans to share OS data as it matures. He also said CytomX’s current assumption is that OS would be the primary endpoint for a first pivotal study, adding that there is “no real precedent” for PFS as a sole primary endpoint in late-line CRC.
When asked about potential comparators, McCarthy pointed to bevacizumab plus Lonsurf as the current standard of care in third line and said the company would look at that as it considers trial design. CytomX said it plans to share additional Phase 1 data, including dose optimization results and registrational study design, in the second half of 2026, with registrational studies targeted to start in the first half of 2027.
McCarthy also said CytomX has initiated a Phase 1 assessment of Varseta in combination with bevacizumab and anticipates initial data late 2026 or early 2027, and announced an intention to begin combination work with bevacizumab plus chemotherapy by the end of 2026. He added the company is working to start its first clinical study outside of CRC later in 2026, while noting EpCAM is expressed across many solid tumors and the company has previously highlighted gastrointestinal tumors such as gastric and pancreatic, as well as lung, ovarian, and certain breast cancers.
About CytomX Therapeutics (NASDAQ:CTMX)
CytomX Therapeutics, Inc is a clinical-stage biopharmaceutical company focused on the discovery and development of next-generation therapeutics based on its proprietary Probody® platform. The company engineers masked antibody prodrugs that remain inactive in healthy tissue but are selectively activated in the tumor microenvironment. This approach is designed to enhance the safety and tolerability of antibody-based therapies, particularly those targeting immuno-oncology pathways.
At the core of CytomX’s pipeline is Pacmilimab (CX-072), an anti–PD-L1 Probody therapeutic currently undergoing clinical evaluation for multiple solid tumor indications.
