A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer
- Conditions
- Triple Negative Breast Neoplasms
- Interventions
- Registration Number
- NCT03742102
- Lead Sponsor
- AstraZeneca
- Brief Summary
This study is designed to determine the efficacy and safety of durvalumab in combination with novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel for first-line metastatic triple negative breast cancer
- Detailed Description
This is a Phase IB/II, 2-stage, open-label, multicenter study to determine the efficacy and safety of durvalumab in combination with novel oncology therapies (i.e. therapies designed for immune modulation) with or without paclitaxel and durvalumab + paclitaxel as first-line treatment in patients with metastatic triple negative breast cancer (TNBC). The study is designed to concurrently evaluate potential novel treatment combinations with clinical promise using a 2-stage approach. The study will use a Simon 2-Stage design to evaluate which cohorts may proceed to expansion.
Part 1 is a Phase IB study of safety and initial efficacy, and Part 2 may expand patient enrollment if adequate efficacy signal is observed in Part 1. The treatment regimens evaluated in Part 2 will depend on the evaluation of safety and efficacy outcomes in Part 1.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 243
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 Paclitaxel durvalumab + paclitaxel + capivasertib Arm 2 Durvalumab durvalumab + paclitaxel + capivasertib Arm 2 Capivasertib durvalumab + paclitaxel + capivasertib Arm 7 Durvalumab durvalumab + datopotamab deruxtecan Arm 1 Paclitaxel durvalumab + paclitaxel Arm 1 Durvalumab durvalumab + paclitaxel Arm 5 Durvalumab durvalumab + paclitaxel + oleclumab Arm 5 Paclitaxel durvalumab + paclitaxel + oleclumab Arm 6 Durvalumab durvalumab + trastuzumab deruxtecan Arm 6 Trastuzumab deruxtecan durvalumab + trastuzumab deruxtecan Arm 8 Durvalumab durvalumab + datopotomab deruxtecan (patients with PD-L1 positive status) Arm 5 Oleclumab durvalumab + paclitaxel + oleclumab Arm 7 Datopotamab deruxtecan durvalumab + datopotamab deruxtecan Arm 8 Datopotamab deruxtecan durvalumab + datopotomab deruxtecan (patients with PD-L1 positive status)
- Primary Outcome Measures
Name Time Method Incidence of adverse events Part1: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Part 2: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Part 1: Assessment of safety and tolerability of each treatment arm
Part 2:
Endpoints based on Investigator assessment according to RECIST 1.1: ORR (objective response rate): The percentage of evaluable patients with a confirmed Investigator-assessed visit response of CR (complete response) or PR (partial response).Laboratory findings Part 1: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Part 2:From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Assessment of safety and tolerability of each treatment arm
- Secondary Outcome Measures
Name Time Method Presence of anti-drug antibodies (ADAs) for durvalumab and applicable novel oncology therapies From cycle 1 day 1 until cycle 7 day 1 (Arms 1-5), from cycle 1 day 1 until cycle 8 day 1 (Arms 6-8) (each cycle is 28 days) and every 12 weeks thereafter until study completion approx. 30 months Investigation of the immunogenicity of durvalumab and novel oncology therapies in all applicable treatment arms Applicable for Part 1 (Arms 1-8) and for Part 2 (Arm 7)
Progression-free survival (PFS 6) On-study tumor assessments occur every 8 weeks until week 48 (Arms 1-5), every 6 weeks until week 48 (Arms 6-8) and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months PFS at 6 months following date of first dose Applicable for Part 2
Serum concentration of durvalumab and serum or plasma concentration of novel oncology therapies From cycle 1 day 1 until cycle 7 day 1 (Arms 1-5), from cycle 1 day 1 until cycle 8 day 1 (Arms 6-8) (each cycle is 28 days) and every 12 weeks thereafter until study completion approx. 30 months Assessment of pharmacokinetics (PK) Applicable for Part 1 (Arms 1-8) and for Part 2 (Arm 7)
Objective response rate (ORR) Approx. 30 months Assessment of the efficacy of each treatment arm according to RECIST 1.1. ORR: The percentage of evaluable patients with a confirmed Investigator-assessed response of CR (complete response) or PR (partial response) Applicable for Part 1 and Part 2.
Duration of response (DoR) On-study tumor assessments occur every 8 weeks (Arms 1-5), every 6 weeks (Arms 6-8) until week 48 and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months Assessment of the efficacy of each treatment arm according to RECIST 1.1. DoR: Time from date of first detection of objective response (which is subsequently confirmed) until the date of objective radiological disease progression Applicable for Part 1 and Part 2
Progression-free survival (PFS). On-study tumor assessments occur every 8 weeks (Arms 1-5),every 6 weeks (Arms 6-8) until week 48 and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months Assessment of the efficacy of each treatment arm according to RECIST 1.1. PFS: Time from date of first dose until the date of objective radiological disease progression or death (by any cause in the absence of progression)
Applicable for Part 1 and Part 2Overall survival (OS) Approx. 30 months OS: Time from date of first dose until the date of death by any cause
Applicable for Part 1 and Part 2
Trial Locations
- Locations (1)
Research Site
🇬🇧Oxford, United Kingdom