Trial results for the Phase 1/2 study investigating APX005M in combination with pembrolizumab (Keytruda) for metastatic melanoma were posted on ClinicalTrials.gov on 2025-11-21. The terminated study reported an Overall Response Rate (ORR) as high as 66.7% in one dose escalation group.

Background

This study evaluated pembrolizumab (Keytruda), a systemic therapy, combined with APX005M, an investigational agent, for patients with metastatic melanoma. APX005M is not FDA approved. The study aimed to assess the combination's safety, tolerability, and potential to control metastatic melanoma.

Trial design

The Phase 1/2 study (NCT02706353) enrolled 34 participants with metastatic melanoma. Part 1 determined the highest tolerable dose of APX005M with pembrolizumab, while Part 2 assessed the combination's ability to control metastatic melanoma and its safety. The study's overall status is TERMINATED. Primary outcome measures were not provided.

Key results

The posted results included findings on safety, tolerability, overall response rate (ORR), and intratumoral CD8⁺ T cell evaluation.

The dose identified for safety and tolerability for both Phase 1: Dose Escalation and Phase 2: Dose Expansion was 10 mg of APX005M.

Overall Response Rate (ORR) in Phase 1: Dose Escalation ranged from 0 percentage of participants at 0.1 mg and 0.5 mg doses, to 33.3 percentage of participants at 1 mg, peaking at 66.7 percentage of participants at 3 mg, and 50 percentage of participants at 10 mg. In Phase 2: Dose Expansion, the ORR was 50 percentage of participants.

Evaluation of Intratumoral CD8⁺ T Cells in Phase 1: Dose Escalation showed varying mean densities. For example, the mean density was 12.04 density cells/mm^2 at 0.1 mg and 1409.18 density cells/mm^2 at 0.5 mg. At 1 mg, it was -24.62 density cells/mm^2 (Standard Deviation: 42.21), and at 3 mg, it was 17.60 density cells/mm^2 (Standard Deviation: 68.98).

What this means

The Phase 1/2 study results suggest the APX005M and pembrolizumab combination demonstrated an Overall Response Rate in metastatic melanoma patients, peaking at 66.7% in the 3 mg dose group. The identified safe dose for APX005M was 10 mg. While these ORR figures indicate potential activity, the study's termination implies further development of this specific combination may have ceased due to factors not detailed in these posted outcomes.

Source

The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT02706353, titled "APX005M in Combination With Systemic Pembrolizumab in Patients With Metastatic Melanoma," were posted on 2025-11-21 on clinicaltrials.gov.