Abstract CT212: Phase Ib/II, global, open-label, randomized evaluation of atezolizumab (atezo) + etrumadenant (etruma) + chemotherapy (chemo) vs chemo alone in MORPHEUS-PDAC

Abstract Background: Adenosine signaling can suppress the immune microenvironment and promote tumor immunity in many cancers, including pancreatic ductal adenocarcinoma (PDAC). Etruma, a dual adenosine A2a/A2b receptor antagonist, was evaluated in combination with atezo (anti-programmed death-ligand 1 PD-L1 antibody) and chemo vs chemo alone (control) in patients (pts) with first-line PDAC in the MORPHEUS-PDAC study (NCT03193190). Methods: Pts were randomized to receive atezo (840 mg IV; Days 1 and 15 of 28-day cycles) + etruma (150 mg orally once daily) + chemo (nab-paclitaxel 125 mg/m2 IV and gemcitabine 1000 mg/m2 IV; Days 1, 8 and 15 of 28-day cycles), or chemo alone, until unacceptable toxicity or loss of clinical benefit. The primary efficacy endpoint was ORR. Key secondary endpoints were PFS, OS, DOR and DCR. Long-term safety results and exploratory biomarkers were examined. Results: Sixteen pts were randomized to atezo + etruma + chemo (15 treated) and 21 to chemo (20 treated). Baseline demographics were generally similar between arms. At 108 weeks, confirmed ORR was 26. 7% (n=4) for atezo + etruma + chemo and 45. 0% (n=9) for chemo alone. Median PFS was 8. 21 vs 6. 80 mo, and median OS was 16. 49 vs 12. 12 mo with atezo + etruma + chemo vs chemo, respectively (Table). While based on limited data, there were no clear associations between baseline levels of CD73 or PD-L1 and clinical outcomes. All treated pts had ≥1 treatment-related adverse event (TRAE) ; 3 pts in each arm withdrew from any treatment due to a TRAE, and 2 pts in the chemo arm had Grade 5 AEs. Conclusion: In MORPHEUS-PDAC, the ORR primary endpoint was not met although both median PFS and OS were numerically improved with the combination therapy, suggesting that the addition of etruma and atezo may confer a benefit. Overall, atezo + etruma + chemo was tolerable. Safety of the combination was consistent with the known risks of the individual treatments. TABLE 1. NAND Efficacy Atezo + etruma + chemo (n=15) Chemo (control) (n=20) Confirmed ORR (investigator-assessed RECIST 1. 1), n (%) a 4 (26. 7) 9 (45. 0) 95% CI 7. 8, 55. 1 23. 1, 68. 5 DCR, n (%) 10 (66. 7) 16 (80. 0) 95% CI 38. 4, 88. 2 56. 3, 94. 3 Median PFS (investigator-assessed RECIST 1. 1), mo 8. 2 6. 8 95% CI 5. 9, 11. 1 5. 7, 9. 9 HR (95% CI) 0. 48 (0. 2, 1. 1) DOR, mo 4. 9 5. 4 95% CI 2. 9, NE 2. 8, 8. 2 HR (95% CI) 1. 43 (0. 4, 5. 3) Median OS, mo 16. 5 12. 1 95% CI 9. 6, 19. 7 10. 0, 15. 4 HR (95% CI) 0. 67 (0. 3, 1. 5) Median survival follow-up, mo 16. 5 11. 4 NE, not evaluable. a One unconfirmed responder in the atezo + etruma + chemo arm; 2 unconfirmed responders in the chemo arm. Citation Format: Kyu-Pyo Kim, Mariano Ponz Sarvise, Teresa Macarulla, Angela Alistar, Eileen O'Reilly, Mathew Boakye, Hen Prizant, Trista Xu, Fiona Young, Janet Lau, Do-Youn Oh, Jill Lacy. Phase Ib/II, global, open-label, randomized evaluation of atezolizumab (atezo) + etrumadenant (etruma) + chemotherapy (chemo) vs chemo alone in MORPHEUS-PDAC abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT212.