Abstract CT201: Phase Ib/II open-label, randomized evaluation of atezolizumab + cobimetinib vs control in MORPHEUS-NSCLC (non-small cell lung cancer), MORPHEUS-PDAC (pancreatic ductal adenocarcinoma) and MORPHEUS-GC (gastric cancer)

Background: The MORPHEUS platform comprises multiple Phase Ib/II trials to identify early efficacy signals and safety of treatment combinations across cancers. Within MORPHEUS, atezolizumab (atezo), a PD-L1 inhibitor, was tested in combination with cobimetinib (cobi), a MEK1/2 inhibitor, in patients with advanced/metastatic (m) NSCLC, PDAC or GC. Methods: MORPHEUS-NSCLC (NCT03337698) enrolled patients who had disease progression during or after receiving a platinum-based regimen and a PD-L1/PD-1 checkpoint inhibitor. MORPHEUS-PDAC (NCT03193190) enrolled patients who had received 1 prior line of systematic therapy. MORPHEUS-GC (NCT03281369) enrolled HER2-negative patients who had not received prior chemotherapy. Patients enrolled in the atezo + cobi arms received atezo 840 mg q2w and cobi 40 mg daily on days 1-21 of each 28-day cycle. In MORPHEUS-GC, patients in the atezo + cobi arm also received mFOLFOX6. This arm started with a safety run-in during which cobi 40 mg could be dose escalated to 60 mg. Control treatments were docetaxel (75 mg/m2) in MORPHEUS-NSCLC and mFOLFOX6 or gemcitabine (100 mg/m2) plus nab-paclitaxel (125 mg/m2) in MORPHEUS-PDAC. The MORPHEUS-GC safety run-in did not have a control. Primary endpoints were objective response rate (ORR; investigator-assessed RECIST 1.1) and safety. Results: MORPHEUS-NSCLC (data cutoff, April 10, 2019): 15 patients received atezo + cobi, and 14 patients received control treatment. No responses were observed, and 7 patients had stable disease (SD) as best response in the treatment arm. In the control arm, 3 patients had partial response (PR), and 5 patients had SD as confirmed best response. All treated patients were evaluable for safety, with 67% of atezo + cobi and 93% of control patients experiencing a treatment-related adverse event (TRAE). Updated data from MORPHEUS-NSCLC will be presented. MORPHEUS-PDAC (data cutoff, September 7, 2018): 14 patients received atezo + cobi, and 15 patients received control treatment. There were no responses in either study arm, but 6 patients in the control arm had SD as confirmed best response. All treated patients were evaluable for safety, with 79% of atezo + cobi and 87% of control patients experiencing a TRAE. MORPHEUS-GC (data cutoff, July 11, 2019): 5 patients received atezo + cobi + mFOLFOX6 in the safety run-in after which this arm was terminated (due to internal re-prioritization, no safety concerns identified). Two patients had PR, and 3 patients had SD as confirmed best response. All 5 patients had a TRAE. Biomarker data will also be presented. Conclusions: No superior efficacy signals were identified with atezo + cobi in NSCLC, PDAC or GC. The safety of atezo + cobi was consistent with each agent9s known safety profile, with no new safety signals identified. Citation Format: Byoung Chul Cho, Nathan Bahary, Johanna Bendell, Enriqueta Felip, Melissa Johnson, Yoon-Koo Kang, Farah Louise Lim, Teresa Macarulla, Gulam Manji, Do-Youn Oh, Osama Rahma, Simon Allen, Edward Cha, Denise Cotting, Hans-Joachim Helms, Jan Pintoffl, Pakeeza Sayyed, Xiaosong Zhang, Kyu-pyo Kim. Phase Ib/II open-label, randomized evaluation of atezolizumab + cobimetinib vs control in MORPHEUS-NSCLC (non-small cell lung cancer), MORPHEUS-PDAC (pancreatic ductal adenocarcinoma) and MORPHEUS-GC (gastric cancer) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT201.