Abstract OT2-06-04: MORPHEUS: A phase Ib/II trial platform evaluating the safety and efficacy of multiple cancer immunotherapy combinations in patients with hormone receptor–positive and triple-negative breast cancer
Authors: Yardley DA , Abu-Khalaf M , Boni V , Brufsky A , Emens LA , Gutierrez M , Hurvitz S , Im S-A , Loi S , McCune SL , Schmid P , O'Hear C , Zhang X , Vidal GA 
Published: May 2019

Abstract
Background:
Cancer immunotherapy (CIT) has significantly improved overall survival across multiple tumor types, but only subsets of patients experience durable response with single-agent CIT. Combinations of CIT with targeted therapy or chemotherapy may be needed in order to target multiple cancer immune escape mechanisms simultaneously, thus providing personalized treatment options that extend clinical benefit to more patients. The MORPHEUS platform includes multiple phase Ib/II trials designed to identify early signals of safety and activity of CIT combinations. Using a randomized trial design, multiple CIT combination arms are compared with a single standard-of-care control arm. 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. Here we describe MORPHEUS trials in patients with metastatic or unresectable locally advanced hormone receptor–positive (HR+BC) or triple-negative breast cancer (TNBC), 2 patient populations in need of more treatment options.
Trial design:
MORPHEUS-HR+BC (NCT03280563) will enroll patients with metastatic or unresectable locally advanced HR+BC who have progressed during or after first-line treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor and whose tumors do not express human epidermal growth factor 2 (HER2). MORPHEUS-TNBC (NCT03424005) will enroll patients with metastatic or unresectable locally advanced TNBC who have progressed during or after first-line treatment with chemotherapy. For both studies, key inclusion criteria include Eastern Cooperative Oncology Group performance status of 0-1 (stage 1) or 0-2 (stage 2) and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Key exclusion criteria include prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, and symptomatic, untreated, or actively progressing central nervous system metastases. Patients in both trials will be randomized to one of the CIT atezolizumab combination arms or a control arm (up to 5 arms in HR+BC and up to 6 arms in TNBC). Patients experiencing loss of clinical benefit or unacceptable toxicity in stage 1 may be eligible to switch to a different CIT atezolizumab combination arm in stage 2. Primary endpoints are safety measures and investigator-assessed objective response rate per RECIST v1.1. Progression-free survival, overall survival, duration of response, clinical benefit rate (HR+BC) or disease control rate (TNBC) are among the secondary endpoints. Exploratory biomarkers will also be examined.
Citation Format: Yardley DA, Abu-Khalaf M, Boni V, Brufsky A, Emens LA, Gutierrez M, Hurvitz S, Im S-A, Loi S, McCune SL, Schmid P, O'Hear C, Zhang X, Vidal GA. MORPHEUS: A phase Ib/II trial platform evaluating the safety and efficacy of multiple cancer immunotherapy combinations in patients with hormone receptor–positive and triple-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-06-04.