On March 16, 2026 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, reported positive Phase 1 expansion data for its EpCAM PROBODY ADC, varsetatug masetecan (Varseta-M) in late-line metastatic CRC. The preliminary data are as of a January 16, 2026 data cutoff from the ongoing CTMX-2051-101 Phase 1 study.

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"These latest Phase 1 data reinforce the potential of Varseta-M to meaningfully improve the standard of care in late-line colorectal cancer. We are now planning interactions with the FDA to discuss the initial registrational path for bringing this highly innovative, first-in-class ADC to the market in late-line CRC," said Sean McCarthy, D. Phil, chief executive officer and chairman of CytomX.

McCarthy added, "Our ultimate vision is to reach a broad CRC patient population with Varseta-M, including in earlier lines of treatment, as well as to expand into additional EpCAM-expressing cancers. We aim to aggressively advance this novel therapy towards late-stage development for the benefit of patients as we set our sights on building CytomX into a commercial-stage company."

"Patients with late-stage metastatic CRC face a poor prognosis and have very limited treatment options. 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, supporting its promise as a potential new treatment option for advanced CRC," said Dr. Kimmie Ng, Associate Chief of the Division of Gastrointestinal Oncology at Dana-Farber Cancer Institute.

Varsetatug Masetecan Phase 1 Expansion Data Summary in Advanced, Late-line Colorectal Cancer

The CTMX-2051-101 study was initiated in April 2024 with dose escalation proceeding through seven dose levels ranging from 2.4 mg/kg to 12 mg/kg. As of the data cutoff of January 16th 2026, a total of 93 patients with late-line metastatic CRC had been enrolled in the study. 60 patients were enrolled across the Phase 1 expansion dose range of 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg of which 56 were efficacy evaluable as of the data cutoff.
Starting in October 2025, the expansion doses of 8.6 mg/kg and 10 mg/kg were prioritized for dose optimization utilizing optimized adverse event management guidelines and adjusted ideal body weight (AIBW) dosing. 20 patients had been enrolled in expanded dose optimization as of the January 16th data cutoff towards an enrollment goal of 40 patients.

Patient Characteristics:

Patients enrolled in the study had previously received a median of 3 prior lines of therapy in the metastatic setting and 96% of patients had previously been treated with irinotecan. 76% of patients had liver metastases and 71% had KRAS mutations.
Patients were not preselected based on EpCAM expression levels. All patients with evaluable tumor biopsies had high EpCAM levels as measured by immunohistochemistry.1

Efficacy:

As of the data cutoff, 56 patients were efficacy-evaluable at the expansion doses of 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg Q3W. Median duration of follow-up across the efficacy-evaluable patient population was approximately 8 months. Efficacy data across the Phase 1 Expansion doses are summarized below in Table 1.

Table 1. Varseta-M Efficacy Summary by Phase 1 Expansion Dose

7.2 mg/kg 8.6 mg/kg 10 mg/kg
Confirmed
Overall Response Rate (ORR)2 6% (1/17) 20% (4/20) 32% (6/19)
Median Progression Free Survival (PFS) 5.5 mo.
(95% CI: 2.5, NE) 6.8 mo.
(95% CI: 2.8, NE) 7.1 mo.
(95% CI: 3.9, NE)
Disease Control Rate (DCR) 88% (15/17) 90% (18/20) 84% (16/19)

At the 8.6 mg/kg dose, the confirmed response rate was 20% with an estimated median PFS of 6.8 months and at the 10 mg/kg dose, the confirmed response rate was 32% with an estimated median PFS of 7.1 months.
The disease control rate was 88% (49/56) across the expansion doses of 7.2 – 10 mg/kg.
The doses of 8.6 mg/kg and 10 mg/kg have been prioritized for further evaluation with the goal of selecting a dose or doses for a registrational study.
Dose optimization at 8.6 mg/kg and 10 mg/kg utilizing AIBW dosing and updated prophylaxis for adverse event management is ongoing.
At the doses of 11 mg/kg Q3W and 12 mg/kg Q3W, which were not expanded for further evaluation, the overall response rate was 30% (3/10).

Safety:

As of the data cutoff, 93 patients were evaluable for safety including 80 patients across the expansion dose range of 7.2 mg/kg to 10 mg/kg. Varseta-M’s safety profile was generally consistent with data presented in Phase 1 dose escalation. Most treatment related adverse events were Grade 1 or Grade 2 in severity.

No interstitial lung disease, febrile neutropenia or pancreatitis were observed.
The most common treatment-related adverse event (TRAE) was diarrhea which was generally manageable and reversible.
In Phase 1 dose expansions starting in Q2 2025, prophylactic strategies for diarrhea management were investigated. In dose optimization starting in Q4 2025, an updated prophylaxis regimen of anti-motility medication (loperamide or diphenoxylate/atropine) plus budesonide was implemented.3
In the 20 patients receiving the updated prophylactic regimen in dose optimization at doses of 8.6 mg/kg and 10 mg/kg, Grade 3 diarrhea was 10%.4,5
Overall, as of the January 16th 2026 data cutoff, in the 80 patients treated at expansion and optimization doses ranging between 7.2 mg/kg to 10 mg/kg, the most common treatment-related adverse events (TRAEs) were diarrhea (68 pts, 19 Gr 3), nausea (44 pts, 4 Gr 3), vomiting (29 pts, 3 Gr 3), fatigue (32 pts, 2 Gr 3), hypokalemia (21 pts, 13 Gr 3+), and anemia (13 pts, 6 Gr 3). Serious treatment related adverse events (SAEs) in > 1 patient included diarrhea (4), vomiting (3), hypokalemia (3), dehydration (3), acute kidney injury (2), and colitis (2).
As previously reported on August 13, 2025, there was one treatment-related grade 5 acute kidney injury (AKI) in a patient treated at the 7.2 mg/kg dose. The patient had a complex medical history including having a solitary kidney, and the AKI was determined to be secondary to Grade 3 nausea and Grade 2 diarrhea. No other Grade 5 TRAEs have been reported as of the January 16th 2026 data cutoff.
At the 11 mg/kg and 12 mg/kg doses, there were no dose limiting toxicities in dose escalation. The most common TRAEs across the patients in the 11 mg/kg dose (n=8) and 12 mg/kg dose (n=3) were diarrhea (9 pts, 6 GR 3), nausea, (8 pts, 0 Gr 3), and vomiting (8 pts, 1 Gr 3). Patients treated at the 11 and 12 mg/kg doses did not receive the optimized prophylactic regimen or adjusted ideal body weight dosing.

Varsetatug Masetecan Next Steps:

Additional efficacy and safety data from the Phase 1 study are expected to be presented at one or more medical meetings in 2026.
The Company aims to align with the FDA in 2026 on a potential registrational study design for Varseta-M monotherapy in advanced CRC.
A Phase 1 Varseta-M combination study with bevacizumab in CRC has been initiated and a Phase 1b/2 study in combination with bevacizumab and chemotherapy is expected to start by the end of 2026.
Initiation of Phase 1 expansion cohort(s) in additional EpCAM-expressing indications is planned for 2H 2026.

(Press release, CytomX Therapeutics, MAR 16, 2026, View Source [SID1234663565])