Trial results for the Phase 2 study (NCT03049618) investigating pembrolizumab in combination with recombinant EphB4-HSA fusion protein were posted on ClinicalTrials.gov on 2025-10-22. The study reported an Overall Response Rate (ORR) of 6 participants in the Head and Neck Cancer Cohort and 3 participants in the Non-Small Cell Lung Cancer Cohort.
Background
The study investigated the combination of pembrolizumab (also known as Keytruda), a monoclonal antibody, with recombinant EphB4-HSA fusion protein. Pembrolizumab is known to interfere with the ability of cancer cells to grow and spread, while recombinant EphB4-HSA fusion protein may inhibit tumor cell growth by blocking enzymes necessary for cell proliferation. This Phase 2 trial focused on patients with non-small cell lung cancer that had spread, or head and neck squamous cell cancer that had recurred or spread to other parts of the body.
Trial design
The Phase 2 study, NCT03049618, titled "Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475," was a completed trial that enrolled 42 participants. The trial investigated the combination of recombinant EphB4-HSA fusion protein and pembrolizumab in patients with non-small cell lung cancer (NSCLC) that had spread, or head and neck squamous cell cancer (HNSCC) that had recurred or spread. Specific conditions for enrollment included those with ALK Gene Mutation, BRAF Gene Mutation, EGFR Gene Mutation, Head and Neck Squamous Cell Carcinoma, and Metastatic Head and Neck Carcinoma.
Key results
The trial results provided insights into the efficacy and safety of the combination therapy across two cohorts. For the Head and Neck Cancer Cohort:
- The Overall Response Rate (ORR) was observed in 6 participants.
- The median Duration of Response was 3.7 months (95% Confidence Interval).
- The median Overall Survival (OS) was 8.6 months (95% Confidence Interval).
- The median Progression Free Survival (PFS) was 2.6 months (95% Confidence Interval).
- 25 participants experienced adverse events.
For the Non-Small Cell Lung Cancer Cohort:
- The Overall Response Rate (ORR) was observed in 3 participants.
- The median Duration of Response was 7.6 months (95% Confidence Interval).
- The median Overall Survival (OS) was 11.8 months (95% Confidence Interval).
- The median Progression Free Survival (PFS) was 3.0 months (95% Confidence Interval).
- 17 participants experienced adverse events.
Key analyses included:
- Fisher Exact method yielded p-values of 0.34, 0.34, 0.057, and 1 for various outcomes.
- Log Rank method yielded p-values of 0.83 and 0.83 for various outcomes.
What this means
The results from this Phase 2 study indicate that the combination of pembrolizumab and recombinant EphB4-HSA fusion protein elicited objective responses and provided a measurable duration of response, overall survival, and progression-free survival in patients with advanced head and neck squamous cell carcinoma and non-small cell lung cancer. While the observed response rates and survival durations provide preliminary insights into the activity of this combination, the statistical analyses, particularly the p-values from Fisher Exact and Log Rank methods, do not demonstrate strong statistical significance across all measured outcomes. These findings contribute to the understanding of this combination therapy's profile in these challenging cancer types.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03049618, titled "Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475," were posted on 2025-10-22 on clinicaltrials.gov.