MORPHEUS: A phase Ib/II umbrella study platform evaluating the safety and efficacy of multiple cancer immunotherapy (CIT)-based combinations in different tumour types

Abstract

Background: Significant survival benefit has been achieved with CIT across multiple tumour types, but only subsets of patients (pts) experience durable response with CIT monotherapy. Efficacious CIT combinations targeting multiple cancer immune escape mechanisms need to be identified to extend clinical benefit to more pts. The MORPHEUS platform includes multiple Phase Ib/II trials designed to identify early signals of safety and activity of CIT combinations. Using a randomised trial design, multiple CIT combination arms are compared with a single standard‐of‐care control arm. We present 7 tumour type‐specific MORPHEUS trials, each evaluating various CIT combinations that simultaneously enhance immune‐cell priming and activation, tumour infiltration and/or recognition of tumour cells for elimination. Trial design: The MORPHEUS trials described here are global, open‐label, randomised, Phase Ib/II trials enrolling pts with 1 of the following cancers: pancreatic ductal adenocarcinoma (PDAC), gastric or gastro‐oesophageal junction cancers (GC/GEJ), hormone receptor‐positive or triple‐negative breast cancers (HR+/TNBC), non‐small cell lung cancer (NSCLC), or colorectal cancer (CRC) (Table). These trials have the flexibility to open new treatment arms with novel CIT combinations as they become available and to close arms that show minimal activity or unacceptable toxicity. Pts experiencing loss of clinical benefit or unacceptable toxicity may be eligible to switch to a different CIT combination arm. Eligibility requires measurable disease per RECIST v1.1. Further eligibility criteria will be provided. Primary endpoints are safety and investigator‐assessed ORR per RECIST v1.1. Secondary endpoints include PFS, OS, DCR and DOR. Exploratory biomarkers will also be examined.