Trial results for the Morpheus-Melanoma study (NCT05116202) investigating multiple treatment combinations for melanoma, including atezolizumab, were posted on ClinicalTrials.gov on 2025-07-18. In Cohort 1, the combination of atezolizumab + tiragolumab demonstrated a pathologic response rate (pRR) of 45.0%, which was lower than the 77.3% observed in the nivolumab + ipilimumab control arm as determined by independent pathologic review.

Background

The Morpheus-Melanoma study investigated various treatment combinations for patients with melanoma. Atezolizumab is an immunotherapy drug, and this trial explored its efficacy in combination with other agents.

Trial design

The Morpheus-Melanoma study (NCT05116202) was a Phase 1/Phase 2, multi-arm trial enrolling 110 participants with melanoma. It evaluated the efficacy, safety, and pharmacokinetics of various treatment combinations. Cohort 1 included cancer immunotherapy (CIT)-naive participants with resectable Stage III melanoma, and Cohort 2 included participants with Stage IV melanoma. Interventions included nivolumab, ipilimumab, tobemstomig 2100 mg (also referred to as ro7247669 2100 mg), atezolizumab, and tiragolumab in different combinations. The study did not list specific primary outcome measures in the posted results.

Key results

For Cohort 1 (resectable Stage III melanoma), the pathologic response rate (pRR) was assessed by independent pathologic review. The nivolumab + ipilimumab (control) arm showed a pRR of 77.3%. The tobemstomig 2100 mg arm showed a pRR of 80.0%. The atezolizumab + tiragolumab arm demonstrated a pRR of 45.0%. The tobemstomig + tiragolumab arm had a pRR of 60.0%.

Local pathologic assessment for pRR in Cohort 1 yielded similar trends: nivolumab + ipilimumab (control) was 81.8%, tobemstomig 2100 mg was 75.0%, atezolizumab + tiragolumab was 50.0%, and tobemstomig + tiragolumab was 60.0%.

Regarding Event-free Survival (EFS) in Cohort 1, the median EFS for nivolumab + ipilimumab (control) was 19.55 months, and for atezolizumab + tiragolumab it was 22.51 months. The median EFS for tobemstomig 2100 mg was not available (NA).

For Cohort 2 (Stage IV melanoma), the objective response rate (ORR) for the tobemstomig + tiragolumab arm was 0 percentage of participants as determined by the investigator.

Analyses of the difference in pRR compared to the control arm (nivolumab + ipilimumab) showed that for atezolizumab + tiragolumab, the difference in pRR by independent review was -32.27 (95.0% CI: -65.01 to 0.46), and by local assessment was -31.82 (95.0% CI: -63.79 to 0.16).

What this means

The Morpheus-Melanoma trial results indicate varying efficacy profiles for the tested immunotherapy combinations in melanoma. In Cohort 1, the atezolizumab + tiragolumab combination showed a lower pathologic response rate compared to the nivolumab + ipilimumab control arm. While median event-free survival for atezolizumab + tiragolumab was numerically longer, the reduced pRR suggests a complex efficacy outcome for this combination in resectable Stage III melanoma. The tobemstomig 2100 mg monotherapy arm demonstrated a pRR comparable to or slightly higher than the control. The 0% objective response rate for tobemstomig + tiragolumab in Cohort 2 highlights a lack of response in Stage IV melanoma for that specific combination.

Source

The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05116202, titled "A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Melanoma (Morpheus-Melanoma)," were posted on 2025-07-18 on clinicaltrials.gov.