Phase Ib Randomized Open-label Trial of Sacituzumab Govitecan Plus Nivolumab or Sacituzumab Govitecan Plus Nivolumab and Relatlimab as Second-line Therapy for Patients With Metastatic Triple Negative Breast Cancer
Summary
This is a randomized, open-label, phase Ib study to assess safety and efficacy of sacituzumab govitecan plus nivolumab or sacituzumab govitecan plus a fixed dose combination of nivolumab and relatlimab in patients with any programmed cell death-ligand 1 (PD-L1) status metastatic, triple negative breast cancer on routine testing with one prior line of cytotoxic chemotherapy with or without immunotherapy in the metastatic setting. The study treatment will be continued until the progression of disease, unacceptable toxicity, death, or withdrawal of consent for any reason.
Detailed description
This is a randomized, open-label, phase Ib study to assess safety and efficacy of sacituzumab govitecan plus nivolumab or sacituzumab govitecan plus a fixed dose combination of nivolumab and relatlimab in patients with any programmed cell death-ligand 1 (PD-L1) status metastatic, triple negative breast cancer on routine testing with one prior line of cytotoxic chemotherapy with or without immunotherapy in the metastatic setting. The study treatment will be continued until the progression of disease, unacceptable toxicity, death, or withdrawal of consent for any reason. Patients will be followed up for up to two years. Their safety will be monitored, and tumor response will be regularly evaluated by RECIST 1.1 criteria every nine weeks. The primary endpoint includes safety as the incidence of dose-limiting toxicities (DLT) in three weeks after C1D1. Secondary endpoints include overall response rate (defined as either complete response or partial response), duration of response, clinical benefit rate, progression free survival, and safety (TEAE) with sacituzumab govitecan plus nivolumab or sacituzumab govitecan plus nivolumab + relatlimab FDC. Exploratory endpoints include overall survival, and biomarkers of prediction of response will be also evaluated. There will be a 135-day (+7 days) follow-up visit after the last study treatment administration or before starting a new anticancer treatment, whichever occurs first, followed by long-term/survival chart review follow-up every three months (±14 days) from the date of the 135-day (+7 days) follow-up visit for two years.
Arms & interventions
- DrugRelatlimab FDC + Nivolumab
Relatlimab: 360 IV Q3W (Dose level 1) and 120mg IV Q3W (Dose level -1) Nivolumab: 360mg IV Q3W
- DrugSacituzumab Govitecan (SG)
10 mg/kg IV D1 \& D8 every 21-day cycles (Dose level 1); 7.5 mg/kg IV D1 \& D8 every 21-day cycles (Dose level -1); 5 mg/kg IV D1 \& D8 every 21-day cycles 21-day cycles (Dose level -2)
- DrugNivolumab
360mg IV Q3W
Outcome measures
Primary
Incidence and severity of dose limiting toxicities in patients treated with sacituzumab govitecan combinations
The primary outcome measure is the incidence of dose-limiting toxicities (DLTs) observed three weeks after the first cycle of treatment with sacituzumab govitecan in combination with nivolumab, or sacituzumab govitecan in combination with nivolumab and relatlimab fixed-dose combination in patients with advanced triple-negative breast cancer in the second-line setting. The assessment will include the frequency and severity of DLTs to evaluate the safety and tolerability of the treatment regimens.
Time frame: Three weeks post-Cycle 1 Day 1 (each cycle is 21 days)
Secondary
Time to response in patients treated with sacituzumab govitecan combinations
Time frame: At baseline (Week 0), followed by assessments every 9 weeks (Weeks 9, 18, 27, 36, etc.). The final assessment will take place at the end of the trial, during the last follow-up visit, which will occur 4 weeks post-treatment or upon study completion
Overall response rate in patients treated with sacituzumab govitecan combinations
Time frame: At baseline (Week 0), followed by assessments every 9 weeks (Weeks 9, 18, 27, 36, etc.). The final assessment will take place at the end of the trial, during the last follow-up visit, which will occur 4 weeks post-treatment or upon study completion
Duration of response in patients treated with sacituzumab govitecan combinations
Time frame: At baseline (Week 0), followed by assessments every 9 weeks (Weeks 9, 18, 27, 36, etc.). The final assessment will take place at the end of the trial, during the last follow-up visit, which will occur 4 weeks post-treatment or upon study completion
Clinical benefit rate in patients treated with sacituzumab govitecan combinations
Time frame: At baseline (Week 0), followed by assessments every 9 weeks (Weeks 9, 18, 27, 36, etc.). The final assessment will take place at the end of the trial, during the last follow-up visit, which will occur 4 weeks post-treatment or upon study completion
Progression free survival in patients treated with sacituzumab govitecan combinations
Time frame: At baseline (Week 0), followed by assessments every 9 weeks (Weeks 9, 18, 27, 36, etc.). The final assessment will take place at the end of the trial, during the last follow-up visit, which will occur 4 weeks post-treatment or upon study completion
Incidence of adverse events in patients treated with sacituzumab govitecan combinations
Time frame: Days 1 and 8 of every 21-day cycle and at the last follow up visit, 30 days after the last treatment cycle or upon study completion
Frequency of serious adverse events in patients treated with sacituzumab govitecan combinations
Time frame: Days 1 and 8 of every 21-day cycle and at the last follow up visit, 30 days after the last treatment cycle or upon study completion
Incidence of Treatment-Emergent Adverse Events in patients treated with sacituzumab govitecan combinations
Time frame: Days 1 and 8 of every 21-day cycle and at the last follow up visit, 30 days after the last treatment cycle or upon study completion
Incidence of Adverse Events of Special Interest in patients treated with sacituzumab govitecan combinations
Time frame: Days 1 and 8 of every 21-day cycle and at the last follow up visit, 30 days after the last treatment cycle or upon study completion
Incidence of Immune-Mediated Adverse Events in patients treated with sacituzumab govitecan combinations
Time frame: Days 1 and 8 of every 21-day cycle and at the last follow up visit, 30 days after the last treatment cycle or upon study completion
Rate of Treatment Discontinuation Due to Adverse Events in patients treated with sacituzumab govitecan combinations
Time frame: Days 1 and 8 of every 21-day cycle and at the last follow up visit, 30 days after the last treatment cycle or upon study completion
Changes in ECOG Performance Status in patients treated with sacituzumab govitecan combinations
Time frame: Days 1 and 8 of every 21-day cycle and at the last follow up visit, 30 days after the last treatment cycle or upon study completion
Electrocardiogram abnormalities in patients treated with sacituzumab govitecan combinations
Time frame: Days 1 and 8 of every 21-day cycle
Echocardiogram findings in patients treated with sacituzumab govitecan combinations
Time frame: Days 1 and 8 of every 21-day cycle
Eligibility criteria
Study locations (1)
Yale University
New Haven, Connecticut, 06510