A Phase 1b Trial of the Cyclin-dependent Kinase Inhibitor Dinaciclib in Combination With Pembrolizumab in Patients With Advanced Breast Cancer and Assessment of MYC Oncogene Overexpression
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Proportion of participants with reported dose-limiting toxicities (DLTs)
Study Overview
Brief Summary
The purpose of this trial is to determine the safety and tolerability (maximum tolerated dose (MTD)) of weekly dinaciclib in combination with pembrolizumab in patients with advanced breast cancer. Once this is defined, dose expansion will be performed at this MTD in patients with metastatic or locally advanced and unresectable triple negative breast cancer, to evaluate the efficacy of combined dinaciclib and pembrolizumab.
Detailed Description
PRIMARY OBJECTIVE:
I. Define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of dinaciclib
SECONDARY OBJECTIVE:
I. Evaluation of the preliminary efficacy of this combination using RECIST 1.1 and irRECIST.
EXPLORATORY OBJECTIVE:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (Dinaciclib, Pembrolizumab)
Pembrolizumab will be administered on Day 1, every 3 weeks at a fixed dose of 200 mg IV. Dinaciclib will be administered D1 and D8 of a 21 day cycle by 2-hour intravenous infusion starting at Dose Level (DL) 1 of 12 mg/m^2. Further dose escalation cohorts are defined as follows: DL 2: 18 mg/m^2, DL 3: 25 mg/m^2, DL 4: 33 mg/m^2, and DL 5: 50 mg/m^2
Intervention: Dinaciclib (Drug)
Treatment (Dinaciclib, Pembrolizumab)
Pembrolizumab will be administered on Day 1, every 3 weeks at a fixed dose of 200 mg IV. Dinaciclib will be administered D1 and D8 of a 21 day cycle by 2-hour intravenous infusion starting at Dose Level (DL) 1 of 12 mg/m^2. Further dose escalation cohorts are defined as follows: DL 2: 18 mg/m^2, DL 3: 25 mg/m^2, DL 4: 33 mg/m^2, and DL 5: 50 mg/m^2
Intervention: Pembrolizumab (Drug)
Outcomes
Primary Outcomes
Proportion of participants with reported dose-limiting toxicities (DLTs)
Time Frame: Up to 1 cycle (1 cycle is equal to 21 days)
Dose-limiting hematologic and non-hematologic toxicities classified using the CTCAE, will be based on events occurring during the first cycle of study drug administration. To be considered a dose-limiting toxicity, an adverse experience must be related to one or both of the study drugs, and must not be related to disease progression or intercurrent illnesses. Participants must receive Day 1 and Day 8 treatments of dinaciclib during the first cycle in order to be evaluable for DLTs (unless missed doses are due to toxicity).
Maximum tolerated dose (MTD)
Time Frame: Up to 1 cycle (1 cycle is equal to 21 days)
The MTD is determined by the number of dose-limiting toxicities reported by participants in the first cycle of treatment.
Secondary Outcomes
- Overall Response Rate(Up to 3 years)
Investigators
Jo Chien
UCSF Assistant Clinical Professor
University of California, San Francisco