Trial results for a Phase 1/Phase 2 study evaluating multiple atezolizumab-based combinations for metastatic non-small cell lung cancer (NSCLC) were posted on ClinicalTrials.gov on 2026-05-12. The study, NCT03337698, explored various regimens, with one combination, atezolizumab + CEA-TCB, showing an objective response rate of 100% in a first-line cohort.
Background
Atezolizumab (Tecentriq) is an immunotherapy often used in the treatment of various cancers, including non-small cell lung cancer (NSCLC). This study investigated its efficacy in combination with several other agents, such as cobimetinib, CEA-TCB (ro6958688), docetaxel, and CPI-444, in participants with metastatic NSCLC.
Trial design
The Phase 1/Phase 2 Morpheus-NSCLC study (NCT03337698) was a terminated trial that enrolled 314 participants with metastatic non-small cell lung cancer. The study design included two parallel cohorts: Cohort 1 for participants with tumor PD-L1 expression who had received no prior systemic therapy for metastatic NSCLC, and Cohort 2 for participants who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor. The study evaluated the objective response rate as determined by investigator according to RECIST V1.1.
Key results
Key results for objective response rates (OR) in Stage 1 were reported:
- In Stage 1 Cohort 1: Control (Atezolizumab), the OR was 33.3%.
- In Stage 1 Cohort 1: Atezolizumab + Cobimetinib, the OR was 0%.
- In Stage 1 Cohort 1: Atezolizumab + CEA-TCB, the OR was 100%.
- In Stage 1 Cohort 1: Atezolizumab + Tiragolumab, the OR was 0%.
- In Stage 1 Cohort 2: Control (Docetaxel), the OR was 13.1%.
- In Stage 1 Cohort 2: Atezolizumab + Cobimetinib, the OR was 0%.
- In Stage 1 Cohort 2: Atezolizumab + CEA-TCB, the OR was 0%.
- In Stage 1 Cohort 2: Atezolizumab + CPI-444, the OR was 6.7%.
- In Stage 1 Cohort 2: Docetaxel + Atezolizumab, the OR was 6.3%.
- In Stage 1 Cohort 2: Atezolizumab + Ipatasertib, the OR was 6.7%.
- In Stage 1 Cohort 2: Atezolizumab + Bevacizumab, the OR was 20.0%.
- In Stage 1 Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy, the OR was 16.7%.
Key analyses on the difference in overall response rates included:
- A difference of -33.33 (95% CI: -100.0, 46.68) for one comparison.
- A difference of -13.11 (95% CI: -25.74, -0.49) for another comparison.
- A difference of -6.45 (95% CI: -25.8, 12.91) for another comparison.
- A difference of -6.86 (95% CI: -25.38, 11.66) for another comparison.
- A difference of -6.45 (95% CI: -21.24, 8.34) for another comparison.
- A difference of 6.89 (95% CI: -10.2, 23.97) for another comparison.
What this means
The posted results from the terminated Phase 1/Phase 2 Morpheus-NSCLC study reveal highly varied objective response rates across different atezolizumab-based combinations in metastatic non-small cell lung cancer. While atezolizumab + CEA-TCB demonstrated a notable 100% OR in the first-line Cohort 1, other combinations, such as atezolizumab + cobimetinib and atezolizumab + tiragolumab in Cohort 1, and atezolizumab + cobimetinib and atezolizumab + CEA-TCB in Cohort 2, showed 0% OR. The termination of the study suggests that the overall development strategy for these specific combinations may be impacted, despite some promising individual results. The wide range of responses underscores the complexity of identifying effective combination therapies in NSCLC.
Source
The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT03337698, titled "A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer (Morpheus- Non-Sma", were posted on 2026-05-12 on clinicaltrials.gov.