Trial results for the Phase 1/2 study investigating TAK-981 given with pembrolizumab in participants with select advanced or metastatic solid tumors were posted on ClinicalTrials.gov on 2025-12-10. The study reported varying numbers of treatment-emergent adverse events (TEAEs) and dose-limiting toxicities (DLTs) across different dose escalation groups, with up to 33 participants experiencing TEAEs in one group.
Background
The study aimed to evaluate the safety, tolerability, and preliminary efficacy of TAK-981 in combination with pembrolizumab for participants with advanced or metastatic solid tumors.
Trial design
The study (NCT04381650) was a Phase 1/Phase 2 trial that enrolled 161 participants with advanced or metastatic solid tumors. The interventions included TAK-981 and pembrolizumab, administered in 21-day cycles for up to 24 months or until discontinuation criteria were met. The study's aims included evaluating the safety, tolerability, and preliminary efficacy of the combination treatment.
Key results
The trial results focused on safety and tolerability outcomes across different dose escalation groups for TAK-981:
- For "Phase 1: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs)":
- In the Dose Escalation: TAK-981 40 mg group, 3 participants experienced one or more TEAEs.
- In the Dose Escalation: TAK-981 60 mg group, 6 participants experienced one or more TEAEs.
- In the Dose Escalation: TAK-981 90 mg group, 33 participants experienced one or more TEAEs.
- In the Dose Escalation: TAK-981 120 mg group, 19 participants experienced one or more TEAEs.
- For "Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)":
- In the Dose Escalation: TAK-981 40 mg group, 0 participants experienced DLTs.
- In the Dose Escalation: TAK-981 60 mg group, 0 participants experienced DLTs.
- In the Dose Escalation: TAK-981 90 mg group, 2 participants experienced DLTs.
- In the Dose Escalation: TAK-981 120 mg group, 1 participant experienced DLTs.
- For "Phase 1: Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)":
- In the Dose Escalation: TAK-981 40 mg group, 0 participants experienced Grade 3 or higher TEAEs.
- In the Dose Escalation: TAK-981 60 mg group, 2 participants experienced Grade 3 or higher TEAEs.
- In the Dose Escalation: TAK-981 90 mg group, 20 participants experienced Grade 3 or higher TEAEs.
- In the Dose Escalation: TAK-981 120 mg group, 15 participants experienced Grade 3 or higher TEAEs.
What this means
The reported safety data from this Phase 1/2 trial indicate that the combination of TAK-981 with pembrolizumab exhibits a dose-dependent safety profile in participants with advanced or metastatic solid tumors. Higher doses of TAK-981 (90 mg and 120 mg) were associated with increased occurrences of treatment-emergent adverse events, including Grade 3 or higher events, and dose-limiting toxicities, compared to lower doses. These findings provide initial insights into the tolerability of this combination therapy.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04381650, titled "A Study of TAK-981 Given With Pembrolizumab in Participants With Select Advanced or Metastatic Solid Tumors," were posted on 2025-12-10 on clinicaltrials.gov.