Trial results for the Phase 1 study (NCT03239145) investigating the combination of pembrolizumab and trebananib in patients with advanced solid tumors were posted on ClinicalTrials.gov on 2026-03-12. The study successfully established a maximum tolerated dose (MTD) for trebananib at 30 mg/kg when combined with pembrolizumab, with zero dose-limiting toxicities observed in the dose escalation phases.
Background
Pembrolizumab (Keytruda) is an anti-PD-1 therapy, while trebananib (AMG386) targets Angiopoietin-2 (Ang-2). This study explored their combination as a potential treatment for advanced solid tumors, including melanoma, ovarian, renal, or colorectal cancer.
Trial design
The Phase 1 study (NCT03239145) was a completed trial that enrolled 62 participants with advanced solid tumors. The investigation focused on the combination of pembrolizumab and trebananib. The study aimed to evaluate this investigational combination as a possible treatment for advanced solid tumors, specifically mentioning melanoma, ovarian, renal, or colorectal cancer.
Key results
The trial results focused on safety and preliminary efficacy in the dose escalation and expansion cohorts. For the dose escalation phase:
- The "Number of Participants Experienced Dose Limit Toxicities (DLT)" was 0 Participants for both "[Dose Escalation Dose Level I] Pembrolizumab + Trebananib" and "[Dose Escalation Dose Level II] Pembrolizumab + Trebananib".
- The "Maximum Tolerated Dose (MTD) of Trebananib" was established at 30 mg/kg for the combination with pembrolizumab.
In the dose expansion cohort, the "Grade 3 or Higher Toxicity Rate in Expansion Cohort" was observed as:
- 59.5 percentage of participants (90% Confidence Interval) for colorectal cancer.
- 63.6 percentage of participants (90% Confidence Interval) for ovarian cancer.
- 75.0 percentage of participants (90% Confidence Interval) for renal cell carcinoma.
Regarding preliminary efficacy, the "Objective Response Rate (ORR)" was reported as:
- 7.5 percentage of participants (90% Confidence Interval) for colorectal cancer.
- 9.1 percentage of participants (90% Confidence Interval) for ovarian cancer.
- 0 percentage of participants (90% Confidence Interval) for renal cell carcinoma.
The "Progression Free Survival at 6 Months (PFS6)" was:
- 13 percentage probability (90% Confidence Interval) for colorectal cancer.
- 9 percentage probability (90% Confidence Interval) for ovarian cancer.
- 50 percentage probability (90% Confidence Interval) for renal cell carcinoma.
What this means
The successful establishment of a maximum tolerated dose (MTD) of 30 mg/kg for trebananib in combination with pembrolizumab, alongside the absence of dose-limiting toxicities in the escalation phase, indicates a manageable safety profile for the combination at these initial dose levels. However, the observed "Grade 3 or Higher Toxicity Rate" in the expansion cohorts, ranging from 59.5% to 75.0% across different tumor types, suggests a notable level of higher-grade adverse events in the expanded population. The objective response rates were relatively low, particularly 0% for renal cell carcinoma, while progression-free survival at 6 months showed variability, with 50% for renal cell carcinoma being the highest among the specific tumor types. These findings provide crucial safety and preliminary efficacy data for future development of this combination therapy in advanced solid tumors.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03239145, titled "Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor," were posted on 2026-03-12 on clinicaltrials.gov.