Treatment with the epithelial cell adhesion molecule (EpCAM) PROBODY antibody-drug conjugate CX-2051 demonstrated responses in patients with advanced, late-line colorectal cancer, according to interim phase 1 data from the ongoing CTMX-2051-101 study which were shared in a news release from CytomX Therapeutics, Inc.
These interim data demonstrated a confirmed overall response rate of 28% (five of 18 patients) per RECIST v1.1 criteria among study participants treated with doses for expansion, including 7.2 milligrams per kilogram (mg/kg), 8.6 mg/kg and 10 mg/kg administered every three weeks. These outcomes are important to note, according to the news release, because current overall response rates for approved treatments in the third-or-later-line setting for colorectal cancer are in the low to mid-single digit percentages.
Notably, at the upper expansion dose of 10 mg/kg, three of seven evaluable patients (43%) achieved confirmed responses. The disease control rate was 94% (17 of 18 patients) across all three dose groups.
As of the data cutoff on April 7, 2025, the median progression-free survival was 5.8 months. Furthermore, the safety profile appears favorable, and no dose-limiting toxicities were observed at the time of data cutoff.
Regarding safety, the safety data were available for all 25 patients and demonstrated a favorable safety profile, with no dose-limiting toxicities observed.
Treatment-related side effects were predominantly grade 1 (mild) or 2 (moderate). The most frequently reported included diarrhea (18 patients; five grade 3 [severe]), nausea (11 patients; one grade 3), vomiting (eight patients; no grade 3), fatigue (eight patients; one grade 3), anemia (five patients; three grade 3), hypokalemia (three patients; one grade 3), neutrophil count decrease (two patients; two grade 3), and neutropenia (two patients; one grade 3). Serious treatment-related side effects occurred in five patients — one with a grade 2 side effect and four with grade 3 side effect. No grade 4 (life-threatening) or 5 (death) treatment-related side effects were reported.
Importantly, there were no observed cases of pancreatitis, interstitial lung disease or febrile neutropenia as of the data cutoff.
Based on these results, initiation of a phase 2 clinical trial is planned for the first half of 2026.
“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 patients [with] colorectal cancer,” Dr. Sean McCarthy, CEO and chairman of CytomX, said in the news release. “CX-2051 is showing impressive, durable anti-tumor activity in late line metastatic colorectal cancer, 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.”
“Importantly, we believe these results validate EpCAM as an oncology target and unlock a broad development opportunity for CX-2051 in colorectal cancer and potentially many other cancer types where EpCAM is expressed. We are excited to rapidly advance CX-2051 for the benefit of patients [with] colorectal cancer and to explore the full potential of this novel antibody-drug conjugate,” Dr. McCarthy added.
More Information on the Phase 1 Investigation
The phase 1a study is evaluating CX-2051 administration every three weeks, with 25 patients treated across dose levels one through five. On the higher dose levels of 7.2 mg/kg, 8.6 mg/kg and 10 mg/kg, a total of 23 patients received treatment. Of these, 18 were considered efficacy-evaluable, having completed at least one post-baseline tumor assessment by the data cutoff.
Patient characteristics reflected a heavily pretreated population, with a median of four prior lines of therapy. Among the 25 treated patients, 64% had liver metastases, 64% harbored KRAS mutations and 96% had microsatellite stable tumors. Importantly, patients were not preselected based on EpCAM expression levels.
Notably, 10 of the 18 efficacy-evaluable patients remained on study treatment at the time of the data cutoff, according to the news release.
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