On May 12, 2025 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, reported positive interim Phase 1 data for its EpCAM PROBODY ADC candidate, CX-2051, in advanced, late-line CRC (Press release, CytomX Therapeutics, MAY 12, 2025, View Source [SID1234652877]). The data are as of an April 7th 2025 data cutoff from the ongoing CTMX-2051-101 Phase 1 study.

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"EpCAM is a high potential and broadly expressed cancer target that has been challenging to drug historically due to expression on normal tissues. We believe we have broken important new ground with our data announced today, which show potential for markedly improved outcomes for CRC patients," said Sean McCarthy, D. Phil, chief executive officer and chairman of CytomX. "CX-2051 is showing impressive, durable anti-tumor activity in late line metastatic CRC, an area of high unmet need and a very difficult tumor to treat. Furthermore, CX-2051 has been generally well tolerated, highlighting the power of CytomX PROBODY masking technology."

Dr. McCarthy added, "Importantly, we believe these results validate EpCAM as an oncology target and unlock a broad development opportunity for CX-2051 in CRC and potentially many other cancer types where EpCAM is expressed. We are excited to rapidly advance CX-2051 for the benefit of CRC patients and to explore the full potential of this novel ADC."

CX-2051 Phase 1a Interim 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 as of April 2025.
25 advanced metastatic CRC patients were treated with CX-2051 across dose levels 1 through 5 as of the April 7, 2025 data cutoff. CX-2051 was administered on a once every three week schedule (Q3W).
The 2.4 mg/kg and 4.8 mg/kg doses were single patient dose escalation cohorts not anticipated to be therapeutically active.
At the 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg doses, 23 patients were treated in total, 18 of whom were efficacy evaluable, having had at least one post-baseline tumor assessment as of the data cutoff.
Patient Characteristics:

The 25 patients enrolled in the study across dose levels 1 through 5 had previously received a median of 4 prior lines of therapy and all patients had previously been treated with irinotecan. 64% of patients had liver metastases, 64% had KRAS mutations, and 96% were microsatellite stable.
Patients were not preselected based on EpCAM expression levels.
Efficacy Results:
As of the data cutoff, 18 patients were efficacy-evaluable at the expansion doses of 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg Q3W.

Overall response rate (ORR):
28% of patients (5/18) achieved confirmed partial RECIST v. 1.1 responses. Overall response rates for currently approved therapies in 3rd line or later CRC are in the low to mid-single digit percentages1.
At the 10 mg/kg dose, 3 of 7 evaluable patients (43%) achieved confirmed partial responses.
The Disease Control Rate2 was 94% across the three dose groups (17/18).
Durability:
Median progression free survival was 5.8 months as of the data cutoff.
10 of 18 patients remained on study treatment as of the data of cutoff.
Safety Results:
As of the data cutoff, 25 patients were evaluable for safety.

CX-2051 was generally well-tolerated with manageable adverse events, with no observed dose limiting toxicities. Most treatment related adverse events (TRAEs) were Grade 1 or Grade 2 in severity.
The most common reported TRAEs were diarrhea (18 patients, 5 Grade 3), nausea (11 patients, 1 Grade 3), vomiting (8 patients, No Grade 3), fatigue (8 patients, 1 Grade 3), anemia (5 patients, 3 Grade 3), hypokalemia (3 patients, 1 Grade 3), neutrophil count decrease (2 patients, 2 Grade 3) and neutropenia (2 patients, 1 Grade 3). TRAEs included serious adverse events in 5 patients (1 Grade 2, 4 Grade 3). No Grade 4 or 5 TRAEs were observed.
No events of pancreatitis, interstitial lung disease or febrile neutropenia were reported at time of data cutoff.
CX-2051 Phase 1 Dose Expansions Initiated:

Dose expansions have been initiated at doses of 7.2 mg/kg, 8.6 mg/kg and 10 mg/kg Q3W.
A total of 20 patients are expected to be enrolled at each dose level to inform the selection of recommended phase 2 dose.
CX-2051 Anticipated Milestones:

CX-2051 Monotherapy for Advanced Late-Line CRC:
Additional Phase 1 data update by Q1 2026
Planning Phase 2 study initiation in 1H 2026
CX-2051 CRC Combinations:
Potential to initiate CX-2051 combination studies in earlier lines of CRC in 2026
CX-2051 Pan-tumor Potential:
Evaluate non-CRC, EpCAM-expressing tumor indications for potential Phase 1b study initiation in 2026
CytomX Investor Event Information
Additional details will be provided on the Company’s Investor Call on May 12, 2025 at 8 a.m. EST. Participants may access the live webcast of the conference call from the Events and Presentations page of CytomX’s website at View Source Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. An archived replay of the webcast will be available on the company’s website for at least 30 days.

About CTMX-2051-101 Study
Additional information about the CTMX-2051-101 study can be found here on clinicaltrials.gov.

About CX-2051 (EpCAM PROBODY ADC)
CX-2051 is an investigational masked, conditionally activated ADC directed toward epithelial cell adhesion molecule (EpCAM) and armed with a topoisomerase-1 inhibitor payload. CX-2051 has potential applicability across multiple EpCAM-expressing epithelial cancers, including CRC, and was discovered in collaboration with ImmunoGen, now part of AbbVie. EpCAM (Epithelial Cell Adhesion Molecule) is a highly expressed but previously undruggable tumor antigen due to expression on normal tissues. CX-2051 is designed to open a therapeutic window for this high potential target and to deliver meaningful anti-cancer activity in solid tumors, including CRC.