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. Clinical trial identification: NCT03193190, NCT03281369, NCT03280563, NCT03424005, NCT03337698. Editorial acknowledgement: Medical writing assistance for this abstract was provided by Steffen Biechele, PhD, of Health Interactions. Legal entity responsible for the study: F. Hoffmann-La Roche AG. Funding: F. Hoffmann-La Roche AG.Table: 1239TiPSummary of Cancer-Type Specific MORPHEUS TrialsCancer TypeCohortNo. of Experimental ArmsaNot all experimental arms may be open at the same time.Countries Currently Targeted for EnrolmentPDAC2L3Germany, South Korea, Spain, United StatesGC and GEJ1L2Germany, South Korea, Spain, Taiwan, United Kingdom, United States2L4HR+ BC2L4France, South Korea, Spain, United Kingdom, United StatesTNBC2L5Australia, France, Germany, South Korea, Spain, United Kingdom, United StatesNSCLC1L2Australia, France, South Korea, Spain, United Kingdom, United States2L+bPatients who have progressed on prior platinum chemotherapy and anti–PD-L1/PD-1 treatment given concurrently or sequentially. CIT, cancer immunotherapy; CRC, colorectal cancer; GC, gastric cancer; GEJ, gastro-oesophageal junction cancer; HR+ BC, hormone receptor–positive breast cancer; NSCLC, non-small cell lung cancer; PD-1, programmed death-1; PDAC, pancreatic ductal adenocarcinoma; PD-L1, programmed death-ligand 1; TNBC, triple-negative breast cancer.5CRC3L2Australia, France, South Korea, Spain, United Kingdom, United Statesa Not all experimental arms may be open at the same time.b Patients who have progressed on prior platinum chemotherapy and anti–PD-L1/PD-1 treatment given concurrently or sequentially. CIT, cancer immunotherapy; CRC, colorectal cancer; GC, gastric cancer; GEJ, gastro-oesophageal junction cancer; HR+ BC, hormone receptor–positive breast cancer; NSCLC, non-small cell lung cancer; PD-1, programmed death-1; PDAC, pancreatic ductal adenocarcinoma; PD-L1, programmed death-ligand 1; TNBC, triple-negative breast cancer. Open table in a new tab Disclosure: I. Chau: Honoraria: Amgen, Gilead Sciences, Lilly, Pfizer, Taiho Pharmaceutical; Consulting or advisory role: Bayer, Bristol-Myers Squibb, Five Prime Therapeutics, Lilly, MSD Oncology, Roche/Genentech, Sanofi; Research funding: Janssen-Cilag (Inst), Lilly (Inst), Merck Serono (Inst), Sanofi (Inst); Travel, accommodations, expenses: Bristol-Myers Squibb, Lilly, Merck Serono, MSD, Sanofi. G.M. Haag: Advisory role: BMS, Taiho, Nordic, Lilly, MSD; Honoraria: Roche, Pfizer; Travel grant: Amgen, Ipsen, BMS; Research funding: Nordic, Taiho Pharmaceuticals. O.E. Rahma: Consulting or advisory role: Celgene, Alcimed, Gfk, Merck, Five Prime Therapeutics, Putnam Associates; Travel, accommodations, expenses: Merck, Clinical Care Options; Honoraria: Merck, Company: Clinical Care Options, MI Bioresearch; Research Funding: Amgen, Merck. D.A. Yardley: Speaker's bureau, Advisory boards: Genentech. B.J. Solomon: Advisory boards: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche/Genentech, Novartis; Honoraria: Bristol-Myers Squibb, AstraZeneca; Grant/research support: Pfizer; Royalty, IP Rights/Patent Holder: Veristrat (Biodesix). Consulting/advisory role (inst): Genentech/Roche, Celgene, Boehringer Ingelheim, AstraZeneca, OncoMed, BerGenBio, Lilly, EMD Serono, Kadmon, Janssen, Mirati Therapeutics, Genmab, Pfizer, AstraZeneca, Sten CentRx, Novartis, Checkpoint Therapeutics, Array BioPharma, Regeneron, Merck, Hengrui Pharmaceutical, Lycera, BeiGene, Tarveda Therapeutics, Loxo, AbbvieBoehringer Ingelheim, Guardant Health, Foundation Medicine, Daiichi Sankyo, Danofi; Research funding to institution: Mersana; Immediate family member: Contract lobbyist: Astellas Pharma, Otsuka. G.A. Vidal: Advisory board: Genentech, Eli Lily, Immunomedics; Sponsored research: PUMA and Celcuit; Speaker: PUMA, AstraZeneca, Novartis, Lilly, Pfizer. P. Schmid: Honoraria: AstraZeneca, Bayer, Boehringer, Celgene, Eisai, Novartis, Pfizer, Puma, Roche/Genentech; Research support/funding: Astellas, AstraZeneca, Medivation, Novartis, Oncogenex, Roche/Genentech (all to instituation). Spouse: Employee: Roche. K. Dimick, S. Mahrus, C. Bleul: Employee: Roche/Genentech. P. Sayyed: Employee and stock: Roche. H. Barak: Employee and stock: Roche/Genentech; Previously employed: Baxalta. E. Cha: Employee and stock: Roche/Genentech. A. Drakaki: Consulting: BMS; Research funds: Kite. All other authors have declared no conflicts of interest.