Trial results for the Morpheus-Pancreatic Cancer study (NCT03193190) investigating multiple atezolizumab-based treatment combinations in metastatic pancreatic ductal adenocarcinoma were posted on ClinicalTrials.gov on 2025-11-21. In Cohort 1, the combination of atezolizumab with chemotherapy and selicrelumab achieved an objective response rate (ORR) of 55.6%, compared to 37.5% for chemotherapy alone.
Background
The Morpheus-Pancreatic Cancer study investigated treatment combinations for participants with metastatic Pancreatic Ductal Adenocarcinoma (PDAC). The study aimed to explore the potential of immunotherapy-based regimens in this challenging cancer type.
Trial design
The Morpheus-Pancreatic Cancer study (NCT03193190) was a Phase 1/2, open-label, multicenter, randomized study that enrolled 341 participants with metastatic Pancreatic Ductal Adenocarcinoma (PDAC). The study was designed to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of immunotherapy-based treatment combinations.
Participants were divided into two cohorts: Cohort 1 for those with no prior systemic therapy for metastatic PDAC, and Cohort 2 for those who had received one line of prior systemic therapy. Interventions included various combinations of atezolizumab with agents such as nab-paclitaxel, gemcitabine, oxaliplatin, leucovorin, and fluorouracil, as well as other investigational agents like selicrelumab, bevacizumab, AB928, tiragolumab, tocilizumab, BL-8040, cobimetinib, PEGPH20, and RO6874281.
Key results
The study evaluated the percentage of participants with objective response (OR) as determined by investigator according to RECIST v1.1. Results for Stage 1 Cohort 1 (no prior systemic therapy) included:
- Control (Chemotherapy: Nab-Paclitaxel and Gemcitabine): 37.5% of participants achieved OR.
- Atezolizumab + Chemotherapy + Selicrelumab: 55.6% of participants achieved OR.
- Atezolizumab + Chemotherapy + Bevacizumab: 48.0% of participants achieved OR.
- Atezolizumab + Chemotherapy + AB928: 26.7% of participants achieved OR.
- Atezolizumab + Chemotherapy + Tiragolumab: 31.7% of participants achieved OR.
- Atezolizumab + Chemotherapy + Tocilizumab: 30.0% of participants achieved OR.
For Stage 1 Cohort 2 (one line of prior systemic therapy), the objective response rates were:
- Control (5-fluorouracil + Leucovorin + Oxaliplatin [mFOLFOX6]): 8.7% of participants achieved OR.
- Control (Nab-Paclitaxel and Gemcitabine): 0% of participants achieved OR.
- Atezolizumab + BL-8040: 0% of participants achieved OR.
- Atezolizumab + Cobimetinib: 0% of participants achieved OR.
- Atezolizumab + PEGPH20: 6.1% of participants achieved OR.
- Atezolizumab + RO6874281 Q3W: 0% of participants achieved OR.
Key analyses for difference in ORR included:
- Difference in ORR for Atezolizumab + Chemotherapy + Selicrelumab vs. Control (Chemotherapy) was 18.06 (95.0% CI: -25.6 to 61.71).
- Difference in ORR for Atezolizumab + Chemotherapy + Bevacizumab vs. Control (Chemotherapy) was 10.5 (95.0% CI: -18.85 to 39.85).
- Difference in ORR for Atezolizumab + Chemotherapy + AB928 vs. Control (Chemotherapy) was -10.83 (95.0% CI: -43.7 to 22.03).
- Difference in Overall Response Rates for Atezolizumab + Chemotherapy + Tiragolumab vs. Control (Chemotherapy) was -5.79 (95.0% CI: -30.58 to 18.99).
- Difference in ORR for Atezolizumab + Chemotherapy + Tocilizumab vs. Control (Chemotherapy) was -7.5 (95.0% CI: -34.19 to 19.19).
- Difference in ORR for Atezolizumab + PEGPH20 vs. Control (mFOLFOX6) was -8.7 (95.0% CI: -25.96 to 8.57).
What this means
The results from the Morpheus-Pancreatic Cancer study indicate varied objective response rates for atezolizumab-based combinations in metastatic pancreatic ductal adenocarcinoma. In patients with no prior systemic therapy (Cohort 1), some combinations, particularly atezolizumab with chemotherapy and selicrelumab, showed a numerically higher objective response rate compared to chemotherapy alone. However, the wide confidence intervals for the differences in ORR suggest considerable variability. For patients who had received one line of prior systemic therapy (Cohort 2), most atezolizumab combinations did not demonstrate an improved objective response rate compared to control regimens, with several combinations showing 0% OR.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03193190, titled "A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)," were posted on 2025-11-21 on clinicaltrials.gov.