Cancer
Conditions
Interventions
Sponsors
F. Hoffmann La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed Informed Consent Form Ability to comply with the study protocol Age 18 years at the time of signing Informed Consent Form Pathologically documented breast cancer that is LAI or MBC Confirmed HER2-positive status Availability of FFPE tumor tissue block of most recent tumor material Disease status-requirements are different for Stage 1 and Stage 2. Eastern Cooperative Oncology Group performance status of 0 to 2 Life expectancy of >6 months Negative hepatitis B surface antigen test at screening Participants must have received at least one prior line of anti-HER2-based therapy for LAI or metastatic disease. Participants must have received prior treatment with an anti-HER2 ADC Participants who experience disease progression during or within 12 months of completing adjuvant or neoadjuvant ADC-containing therapy are eligible. Progression on the last systemic therapy. Prior treatment with a TKI in the neoadjuvant/adjuvant setting is acceptable Hematology: adequate hematologic parameters without transfusion in the week before screening procedures, and independent of erythropoietin. Hemoglobin > 9.0 g/dL Absolute neutrophil count > 1.5 x 109/L (1500/uL) with one exception Platelets > 100 x109/L Renal function: Creatinine clearance > 50 mL/min Liver function: Total serum bilirubin > 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST, SGOT)/alanine aminotransferase (ALT, SGPT) 50% Agreement to adhere to the contraception requirements
Exclusion criteria
Exclusion criteria: Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required. Treatment with investigational therapy within 28 days prior to initiation of study treatment Concurrent anti-cancer treatment Based on screening brain MRI, any of the following criteria for participants with brain metastasis -Progressive neurologic impairment or increased intracranial pressure -Any intracranial lesion that is expected to require immediate local therapy -Requirement for systemic corticosteroids for management of CNS symptoms at a total daily dose of >2 mg of dexamethasone -Requirement for anti-epileptic medication for seizure control, with the exception of stable-dose levetiracetam Previously untreated intracranial lesion of > 2.0 cm Opportunistic infection or progressive (severe) infection, including those requiring treatment with interferon or ribavirin Participants with known active and/or untreated hepatitis B or hepatitis C or chronic liver disease are ineligible. Participants who are known to be positive for HIV Participants who have undergone major surgeries (i.e., laparotomic surgery, thoracotomy surgery), within 4 weeks prior to the initiation of treatment or have planned major surgeries during the trial (excluding biopsy) Participants who have active gastrointestinal disorders (including participants who are unable to swallow oral medications) or other diseases, which may significantly affect the absorption, distribution, metabolism or excretion of RO7771950 History of malignancy within 5 years prior to screening Participants who are currently using any drug or herbal medicine known to strongly inhibit or induce CYP3A4 or CYP2C8 activity Participants who are currently using oral coumarin-derivative anticoagulants Participants who have a known dihydropyridine dehydrogenase (DPD) deficiency Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Population: Participants with HER2-positive LAI/MBC with or without CNS metastases who have failed at least one previous line of treatment. Endpoint: PFS-FAS, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by BICR according to RECIST v1.1 and/or RANO-BM where appropriate. Treatment: Combination of RO7771950 and HX (Experimental arms) versus combination of tucatinib and HX (Control arm). | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory Objectives--I-PFS, defined as the time from randomization to the first occurrence of CNS progression or death from any cause (whichever occurs first), as determined by BICR according to RECIST v1.1 and/or RANO-BM where appropriate. Participants with non-CNS progression as first event will not count as events and will continue to be followed up for CNS metastases. -New CNS metastases-free interval, defined as the time from randomization to the first occurrence of new CNS metastases. Participants with non-CNS metastases will not count as events and participants with progression of baseline CNS metastases be censored at the time of the event. RANO-BM criteria will used to assess the endpoint. -Relationship between biomarkers in blood, plasma, CSF (if applicable), and tumor tissue and efficacy, safety, PK, or other biomarker endpoints. -CSF concentration of RO7771950 and its metabolite(s) at specified timepoints;Population: Participants with HER2-positive LAI/MBC with or without CNS metastases who have failed at least one previous line of treatment. Endpoint: PFS-FAS, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by BICR according to RECIST v1.1 and/or RANO-BM where appropriate. Treatment: Combination of RO7771950 and HX (Experimental arms) versus combination of tucatinib and HX (Control arm). Intercurrent Event (ICE) and handling strategies: 1. Use of NPT prior to any PFS event 2. Study treatment discontinuation for any reason prior to a PFS event (e.g., due to lack of efficacy and/or safety) Handling of ICE: Both ICE will be handled using a treatment policy strategy and all tumor assessment data collected after the ICE will be included in the primary PFS-FAS analysis Population-level summary: Hazard ratio;Population: Same as for primary objective. Endpoint: OS-FAS, defined as the time from randomization to death from any cause. Treatment: Sam | — |
Countries
South Africa
Contacts
Public ContactNathaniel Ramuthaga
Clinical Operations Portfolio Leader
Outcome results
None listed