Abstract CT212: Phase Ib/II, global, open-label, randomized evaluation of atezolizumab (atezo) + etrumadenant (etruma) + chemotherapy (chemo) vs chemo alone in MORPHEUS-PDAC
Authors: Kim Kyu-Pyo , Sarvise Mariano Ponz , Macarulla Teresa , Alistar Angela , O'Reilly Eileen , Boakye Mathew , Prizant Hen , Xu Trista , Young Fiona , Lau Janet , Oh Do-Youn , Lacy Jill 
Published: April 2024

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(7_Suppl):Abstract nr CT212.