CytomX Shares Positive Early Phase 1a Data for CX-904 Monotherapy

CytomX Therapeutics, Inc., a leader in the creation of masked, conditionally activated biologic therapeutics, has announced promising initial results from the ongoing Phase 1a dose escalation study of CX-904, a PROBODY T-cell engager targeting EGFR on cancer cells and CD3 on T cells. The study has shown a favorable safety profile and confirmed anti-cancer activity, particularly in patients with advanced pancreatic cancer.

According to Sean McCarthy, CEO and Chairman of CytomX, the initial data on CX-904 are highly encouraging. The results indicate potential advancements for T-cell engagers in targeting various cancer types, especially those expressing EGFR. McCarthy emphasized that CX-904's ability to induce significant tumor reduction in a difficult-to-treat cancer type, while maintaining a favorable safety profile, marks a significant step forward.

As of April 16, 2024, the study had enrolled 35 patients with various advanced metastatic solid tumors known to express EGFR, including pancreatic, colorectal, non-small cell lung cancer, head and neck squamous cell carcinoma, gastric, and esophageal cancers. These patients had undergone numerous prior treatments, with a median of four previous lines of therapy. The study included both initial non-step dosing cohorts with doses ranging from 0.007 mg to 6 mg and step-dosing cohorts with doses ranging from 5 mg to 10 mg, including tocilizumab prophylaxis. Enrollment in a cohort with a target dose of 15 mg is ongoing.

The safety profile of CX-904 has been favorable, with no cytokine release syndrome (CRS) observed in the step-dosing cohorts. Only Grade 1 CRS was observed in the highest non-step dosing cohort at 6 mg. The most common treatment-related adverse events (TRAEs) included rash, arthralgia, arthritis, pruritis, and vomiting, mostly of low grade. Grade 3 TRAEs included tenosynovitis, arthralgia, arthritis, and rash.

Efficacy data revealed that eight patients experienced measurable tumor reduction. Specifically, two out of six efficacy-evaluable patients with pancreatic cancer had confirmed partial responses, indicating significant tumor reduction. All six efficacy-evaluable pancreatic cancer patients achieved disease control. Among those with a confirmed partial response, one patient on a 6 mg dose showed an 83% tumor reduction, while another on a 5 mg dose showed a 51% tumor reduction and remained on treatment. Another patient maintained stable disease without tumor growth for 3.5 months.

Preliminary pharmacokinetic and pharmacodynamic analyses support the PROBODY TCE mechanism, showing maintained masking in circulation and CD8+ T-cell margination and tumor infiltration. The Phase 1a dose escalation and optimization of CX-904 are ongoing, aiming to determine recommended doses for Phase 2. Further updates on the study are expected by the end of 2024, which will guide discussions with CytomX’s partner, Amgen, regarding the initiation of Phase 1b expansion cohorts in specific EGFR-positive tumor types.

CytomX is dedicated to developing innovative, conditionally activated therapies localized to the tumor microenvironment, with a focus on creating safer, more effective cancer treatments. Their pipeline includes several clinical-stage candidates, such as CX-904, CX-2051, and CX-801, targeting various aspects of tumor biology. CytomX collaborates with multiple leading oncology companies, including Amgen, Astellas, Bristol Myers Squibb, Regeneron, and Moderna, to advance their mission of making conditionally activated treatments a new standard in cancer care.