A Study to Evaluate Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients with Metastatic Triple-Negative Breast Cancer (MORPHEUS-TNBC)
- Conditions
- Triple-negative breast cancer (TNBC)Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2017-002038-21-GB
- Lead Sponsor
- F. Hoffman-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 145
Stage 1
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 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
- Life expectancy>= 3 months
- Availability of a representative tumor specimen that is suitable for determination of Programmed death-ligand 1and/or additional biomarker status via central testing
- 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
Stage 1 and Stage 2
- Measurable disease according to Response Evaluation Criteria in Solid Tumors 1.1
- Tumor accessible for biopsy
- 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, 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 (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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 103
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42
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
- Eligibility only for the control arm
Stage 1 (2L CIT naïve cohort only)
- Prior treatment with capecitabine
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.
- 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
- Major surgical procedure within 4wks
- Treatment with antibiotics or live, attenuated vaccine within 2 wks or 4wks prior to C1D1 respectively
- 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
Ipatasertib (Ipat) - Containing arm (Stage 1)
- Prior treatment with ipat or other Akt inhibitors
- Grade >= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceremia
- History of Type I or Type II diabetes mellitus requiring insulin
- Congenital long QT syndrome or screening QT interval corrected through use of Fridericia’s formula > 480ms
- Treatment with strong CYP3A4 inducers or inhibitors within 2wks or 5 drug-elimination half-lives prior to C1D1.
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.
Bevacizumab (Bev) - Containing arm (Stage 1)
- Inadequately controlled arterial hypertension
- History of hypertensive crisis or hypertensive encephalopathy
- Significant vascular disease within 6 months prior to C1D1
- History of hemoptysis within 1 month prior to C1D1 and abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess and intestinal obstruction and/or clinical signs or symptoms of GI obstruction and intra-abdominal inflammatory process within 6 months prior to C1D1.
- Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to C1D1
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to C1D1; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to C1D1
Selicrelumab (Seli)– containing arm (Stage 1)
- Soluble CD25 > 2xULN
- Serum ferritin > 1000 ng/mL
- Known hereditary or acquired coagulopathy
- Concomitan
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