MORPHEUS: A phase Ib/II multi-trial platform evaluating the efficacy and safety of cancer immunotherapy (CIT)-based combinations in patients (pts) with gastric or pancreatic cancer.

Abstract

TPS530 Background: CIT has demonstrated significant survival benefits across multiple cancers. Despite remarkable success, only subsets of pts derive clinical benefit from CIT monotherapy. Thus, CIT combinations may be needed to address the mechanisms that allow cancers to escape antitumor immunity. However, a large number of potential combinations would have to be tested to identify an effective CIT combination regimen. The MORPHEUS platform consists of multiple, global, open-label, randomized Phase Ib/II trials designed to assess the impact of CIT combination therapies in pts with different tumor types. The randomized trial designs allow comparison of a single control arm vs multiple CIT combination arms. The trials will aid development of CIT combinations by identifying early signals and have the flexibility to open arms with new CIT combinations and close arms that show minimal clinical activity or unacceptable toxicity. Various CIT combinations that simultaneously enhance immune cell priming and activation, tumor infiltration and/or recognition of tumor cells for elimination will be evaluated. Here, we will describe Phase Ib/II trials in pts with gastric or gastroesophageal junction cancer (GC) and metastatic pancreatic ductal adenocarcinoma (mPDAC), both of which represent populations with high unmet medical need. Methods: MORPHEUS-GC (NCT03281369) will enroll 2 cohorts including pts with advanced unresectable or metastatic GC who have not received prior chemotherapy (chemo) or have progressed on platinum- or fluoropyrimidine-based chemo. MORPHEUS-PDAC (NCT03193190) will enroll pts with mPDAC who have progressed on prior chemo. Further eligibility criteria details will be provided. Pts will be randomized to one of the CIT combination arms or a control arm (up to 8 arms across 2 cohorts in GC; 4 arms in PDAC). Pts experiencing loss of clinical benefit or unacceptable toxicity may be eligible to continue on a different CIT combination arm. Primary endpoints are investigator-assessed ORR per RECIST v1.1 and safety. Secondary endpoints include PFS, OS, DCR and DOR. Multiple exploratory biomarkers will also be examined. Clinical trial information: NCT03281369, NCT03193190.