A Study to Evaluate Efficacy and Safety of Multiple Treatment Combinations in Patients with Metastatic Breast Cancer (MORPHEUS-panBC)
- Conditions
- Metastatic breast cancer, including triple negative breast cancer (TNBC), hormone receptor positive breast cancer (HR+ BC), and HER2 positive and HER2 low breast cancer (HER2+/HER2-low BC)MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 23.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.1Level: PTClassification code 10055113Term: Breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002038-21-DE
- Lead Sponsor
- F. Hoffman-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 312
All cohorts Stage 1
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Life expectancy>= 3 months
- Tumor accessible for biopsy
- Availability of a representative tumor specimen that is suitable for determination of Programmed death-ligand 1 and/or additional biomarker status via central testing
All cohorts Stage 1 and Stage 2
- Measurable disease according to Response Evaluation Criteria in Solid Tumors 1.1
- Adequate hematologic and end-organ function
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen during the 14 days prior to initiation of study treatment
- Negative HIV test, hepatitis B surface antigen at screening, and hepatitis C virus (HCV) antibody test or positive HCV antibody test followed by a negative HCV RNA test at screening
- Negative total hepatitis B core antibody (HBcAb) test at screening, or
positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL at screening
- For women of childbearing potential: agreement to remain abstinent or use treatment arm-specific contraceptive measures and agreement to refrain from breastfeeding and donating eggs
- For men: agreement to remain abstinent or use treatment arm- specific contraceptive measures, and agreement to refrain from donating sperm for a treatment arm-specific time period
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, 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 (Atezo), disease progression per RECIST v1.1, or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment
- Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1
TNBC cohorts Stage 1
- Metastatic or inoperable locally advanced, histologically documented TNBC
- For patients in the 1L PD-L1 positive cohort: no prior systemic treatment for metastatic or inoperable locally advanced TNBC
- For patients in the 2L CIT-naïve cohort: Eligible for capecitabine monotherapy
- For patients in the 2L CIT-naïve cohort: Radiologic/objective evidence of recurrence or disease progression after 1L treatment with chemotherapy (chemo) for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer
- For patients in the 1L PD-L1 positive cohort: positive PD-L1 expression, defined as >= 1%of the tumor area occupied by PD-L1- expressing tumor-infiltrating immune cells of any intensity
Hormone Receptor-Positive Cohort Stage 1
- Metastatic or inoperable locally advanced, histologically documented HR+breast cancer, as defined by the ASCO, who had previous lines of treatment for metastatic disease.
- Documented ER+tumor according to ASCO/CAP guidelines, defined as >= 1% of tumor cells stained positive based on the most recent tumor biopsy and assessed locally
- Documented HER2 negativity determined by a local laboratory
- Radiologic/objective evidence of recurrence or progression after the most recent systemic therapy for breast cancer
HER2+/HER2 low Cohort Stage 1
- Histologically or cytologically confirmed and documented adenocarcinoma of the breast
All cohorts Stage 1, 2
- Uncontrolled pleural effusion, pericardial effusion, or ascites
requiring recurrent drainage procedures, tumor-related pain and uncontrolled or symptomatic hypercalcemia
- Symptomatic, untreated, or actively progressing central nervous system metastases.
- Symptomatic active lung disease
- History of leptomeningeal disease, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis or tuberculosis on screening and malignancy other than breast cancer within 2 years prior to screening.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
- History of autoimmune disease or immune deficiency
- Grade >= 3 hemorrhage or bleeding event within 28 days prior to C1D1
- Severe infection within 4 wks prior C1D1 or any active infection
- Major surgical procedure within 4wks
- Treatment with antibiotics or live, attenuated vaccine within 2 wks or 4wks prior to C1D1 respectively
TNBC cohorts Stage 1
- Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies
- Treatment with investigational therapy within 28 days prior to C1D1
- Biologic treatment or other systemic treatment within 2 weeks (wks) prior to C1D1
- Treatment with systemic immunostimulatory agents within 4wks or 5 half-lives of the drug prior to C1D1
- Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at the time of consent
- Eligibility only for the control arm
Stage 1 (2L CIT naïve cohort only)
- Prior treatment with capecitabine
SGN-LIV1A - Containing arm (Stage 1)
- Prior treatment with SGN-LIV1A or MMAE -based biologic
- Grade>= 2 neuropathy
- Radiotherapy within 2wks prior to C1D1
- AST/ALT > 1.5 x ULN, or 3 x ULN if liver metastases present
- Documented history of a cerebrovascular event, unstable angina myocardial infarction, or cardiac symptoms consistent with congestive heart failure, within 6 months prior to study enrollment.
Nab-Paclitaxel-Containing Arms (Stage 1)
- Grade >= 2 neuropathy related to taxanes
Tocilizumab-Containing Arm (Stage 1)
- Preexisting CNS demyelinating or seizure disorders
- History of diverticulitis, chronic ulcerative lower GI disease, or other symptomatic lower GI conditions that might predispose a patient to GI perforation
- Current liver disease unrelated to the underlying cancer diagnosis
- Active current infection or history of recurrent bacterial, viral, fungal, mycobacterial, or other infection, including, but not limited to, TB, atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail bed
- Active TB as documented by a positive purified protein derivative
(PPD) skin test or TB blood test and confirmed by a positive chest X-ray within 3 months prior to initiation of study treatment
- Untreated latent TB
- History of, or currently active, primary or secondary immunodeficiency
Sacituzumab Govitecan- Containing Arm (Stage 1)
- Prior treatment with a topoisomerase 1 inhibitor
Inavolisib-Containing Arms during Stage 1
- Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
- Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that m
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method