A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic or Inoperable Locally Advanced Triple-Negative Breast Cancer (Morpheus-TNBC)
Trial Status: Active
This is a Phase Ib / II, open-label, multicenter, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with metastatic or inoperable locally advanced TNBC who had disease progression during or following first-line metastatic treatment with chemotherapy. The study will be performed in two stages. During Stage 1, participants will be randomized to capecitabine (control) or an atezolizumab-containing doublet or triplet combination. Those who experience disease progression, loss of clinical benefit, or unacceptable toxicity may be eligible to receive a new doublet combination treatment in Stage 2 until loss of clinical benefit or unacceptable toxicity. New treatment arms may be added and / or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.
- Inclusion Criteria Stage 1 - ECOG Performance Status of 0 or 1 - Metastatic or inoperable locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression) - Radiologic/objective evidence of recurrence or disease progression after chemotherapy for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer - Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing - Eligible for capecitabine monotherapy - Life expectancy =/> 3 months, as determined by the investigator - Tumor accessible for biopsy - For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs as outlined for each specific treatment arm - For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm - Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment. - Negative HIV test at screening - Negative hepatitis B surface antigen test - Negative total hepatitis B core antibody (HBcAb) - Negative hepatitis C virus (HCV) antibody test at screening - Measurable disease (at least one target lesion) Inclusion criteria stage 2 - ECOG Performance Status of 0, 1, or 2 - Patients randomly allocated to the control arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity, provided that Medical Monitor approval for entry into Stage 2 is obtained, or disease progression per RECIST v1.1 while receiving control treatment - Patients randomly allocated to an experimental arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab, disease progression per RECIST v1.1, or loss of clinical benefit as determined by the investigator (see Section 188.8.131.52 for details) while receiving Stage 1 treatment - Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible by the investigator) Exclusion Criteria for Stage 1 - Prior treatment with any of the Stage 1 protocol-specified study treatments included in arms that are open at the time of screening, with the exception of capecitabine - Treatment with investigational therapy within 28 days prior to initiation of study treatment - Inability to swallow medication or malabsorption condition that would alter the absorption of orally administered medications - Treatment with sorivudine or its chemically related analogues, such as brivudine - History of severe and unexpected reactions to fluoropyrimidine therapy - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) - Uncontrolled tumor-related pain - Symptomatic, untreated, or actively progressing CNS metastases - History of leptomeningeal disease - Active or history of autoimmune disease or immune deficiency - History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted. - Active tuberculosis - Severe infection within 4 weeks prior to initiation of study treatment - Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment - Significant cardiovascular disease - Prior allogeneic stem cell or solid organ transplantation - History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death - Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study - Pregnancy or breastfeeding, or intention of becoming pregnant during the study - Additional drug-specific exclusion criteria might apply.
University of California San Diego
Moffitt Cancer Center
Contact: Deanna Laine Hogue
Rutgers Cancer Institute of New Jersey
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Thomas Jefferson University Hospital
University of Pittsburgh Cancer Institute (UPCI)
Trial Phase Phase I/II
Trial Type Treatment
- Primary ID CO40115
- Secondary IDs NCI-2018-00650, 2017-002038-21
- Clinicaltrials.gov ID NCT03424005