Trial results for the Morpheus-Head and Neck Cancer study (NCT05459129) investigating atezolizumab in combination with tiragolumab and chemotherapy for locally advanced squamous cell carcinoma of the head and neck were posted on ClinicalTrials.gov on 2025-09-15. The study reported a 50.0% pathologic complete response (pCR) and 100% pathologic response rate (pRR) for the atezolizumab + tiragolumab + chemotherapy arm.
Background
The Morpheus-Head and Neck Cancer study (NCT05459129) is a Phase Ib/II, open-label, multicenter, randomized, umbrella study. It investigated multiple treatment combinations in participants with locally advanced squamous cell carcinoma of the head and neck (SCCHN). The study enrolled treatment-naive participants with resectable Stage III-IVA human papillomavirus (HPV)-negative, programmed death-ligand 1 (PD-L1)-positive SCCHN with measurable disease.
Trial design
The Morpheus-Head and Neck Cancer study (NCT05459129) was a Phase Ib/II, open-label, multicenter, randomized, umbrella study that enrolled 12 participants. The study focused on participants with locally advanced squamous cell carcinoma of the head and neck. Interventions included atezolizumab, tiragolumab, carboplatin, and paclitaxel. The study evaluated outcomes such as pathologic complete response (pCR), pathologic response rate (pRR), objective response rate (ORR), event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS).
Key results
The trial evaluated several key outcomes across the treatment arms:
- Pathologic Complete Response (pCR): The percentage of participants achieving pCR was 16.7% for the Atezolizumab + Tiragolumab arm and 50.0% for the Atezolizumab + Tiragolumab + Carboplatin + Paclitaxel arm. The difference in pCR rates was 33.33% (95.0% CI: -33.23 to 99.9).
- Pathologic Response Rate (pRR): The pRR was 66.7% for the Atezolizumab + Tiragolumab arm and 100% for the Atezolizumab + Tiragolumab + Carboplatin + Paclitaxel arm. The difference in pRR was 33.33% (95.0% CI: -21.05 to 87.72).
- Objective Response Rate (ORR): The ORR was 33.3% for the Atezolizumab + Tiragolumab arm and 50.0% for the Atezolizumab + Tiragolumab + Carboplatin + Paclitaxel arm. The difference in ORR was 16.67% (95.0% CI: -54.99 to 88.32).
- Survival Outcomes: Median Event-Free Survival (EFS), Relapse-Free Survival (RFS), and Overall Survival (OS) were reported as "NA" for both groups. Hazard Ratios (HR) were reported as 0.65 (95.0% CI: 0.11 to 3.91) and 0.9 (95.0% CI: 0.13 to 6.43) for certain analyses, and the difference in Event Free Rate (3 Months Analysis) was 16.67% (95.0% CI: -31.42 to 64.75).
What this means
The results from this Phase Ib/II study suggest that combining atezolizumab, tiragolumab, and chemotherapy (carboplatin and paclitaxel) may lead to higher pathologic complete response and pathologic response rates in patients with locally advanced squamous cell carcinoma of the head and neck compared to the dual combination of atezolizumab and tiragolumab. The 100% pathologic response rate observed in the triple combination arm is a notable finding, although the small sample size of 12 participants indicates these are early-phase results that would require further investigation in larger trials.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05459129, titled "A Study Evaluating Efficacy and Safety of Multiple Treatment Combinations in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (Morpheus-Head and Neck Cancer)," were posted on 2025-09-15 on clinicaltrials.gov.