Study of Oraxol and Pembrolizumab in Subjects With Advanced Solid Tumors
- Registration Number
- NCT03588039
- Lead Sponsor
- Athenex, Inc.
- Brief Summary
This is an open-label, Phase 1 dose-escalation study followed by a 2-arm expansion cohort of Oraxol administered in combination with pembrolizumab.
- Detailed Description
This is a two part study. The dose escalation part will enroll subjects with advanced solid tumors for which pembrolizumab is an FDA-approved therapy, to determine the MTD and identify the recommended phase 2 dose of paclitaxel administered as Oraxol in combination with pembrolizumab. Upon determination of the phase 2 dose, the dose expansion part will enroll subjects with advanced/metastatic gastric/gastro-esophageal, or NSCLC into 2 independent cohorts/arms to further evaluate the activity and safety of the study treatment.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 34
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose escalation-Arm 2 Pembrolizumab During the dose escalation period Oraxol will be administered once daily for 3 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 3 Pembrolizumab During the dose escalation period Oraxol will be administered once daily for 4 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 1 Pembrolizumab During the dose escalation period Oraxol will be administered once daily for 2 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 4 Pembrolizumab During the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 5 Oraxol During the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 5 Pembrolizumab During the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 6 Pembrolizumab During the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose expansion-Gastric/GE Pembrolizumab The dose expansion period will enroll subjects with gastric/gastro-esophageal cancer to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose expansion-NSCLC cancer Pembrolizumab The dose expansion period will enroll subjects with NSCLC to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 1 Oraxol During the dose escalation period Oraxol will be administered once daily for 2 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 2 Oraxol During the dose escalation period Oraxol will be administered once daily for 3 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 3 Oraxol During the dose escalation period Oraxol will be administered once daily for 4 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 4 Oraxol During the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose escalation-Arm 6 Oraxol During the dose escalation period Oraxol will be administered once daily for 5 days per week for 2 weeks followed by 1 week off treatment (2 weeks on and 1 week off). Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose expansion-Gastric/GE Oraxol The dose expansion period will enroll subjects with gastric/gastro-esophageal cancer to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle. Dose expansion-NSCLC cancer Oraxol The dose expansion period will enroll subjects with NSCLC to further evaluate the activity and safety of the study treatment. Oraxol will be administered at the dose determined from part 1 for 2 out of 3 weeks. Pembrolizumab will be administered on Day 1 of each 3-week cycle.
- Primary Outcome Measures
Name Time Method Determination of MTD 3 weeks dose limiting toxicities occuring in the first cycle of therapy
Tumor response rate 24 months Proportion of subjects in each arm and part 2 with confirmed tumor response
- Secondary Outcome Measures
Name Time Method Progression free survival (PFS) 24 months To determine the progression free survival after initiation of treatment with Oraxol in subjects
Overall survival (OS) 24 months To determine the overall survival after initiation of treatment with Oraxol in subjects
Duration of response (DOR) 24 months The duration of response will be measured in subjects associated with Oraxol administered in combination with pembrolizumab in subjects with advanced/metastatic gastric/gastro-esophageal, or NSCLC who have stable disease or progressed on previous anti-PD1 or anti-PDL1 therapy
Pharmacokinetics of Oraxol Day 1 and day 2 Plasma concentrations of Oraxol
Disease Control Rate (DCR) 24 months The disease control rate, defined as the proportion of subjects whose best response is complete response (CR), partial response (PR), or stable disease (SD) divided by the total number of evaluable subjects in each cohort.
Incidence of Adverse Events 24 months The incidence of Treatment Emergent Adverse Events and Treatment-related Adverse Events will be summarised using descriptive statistics.
Time to response 24 months To determine the time to response, defined as the time from the treatment initiation to first documented response
Trial Locations
- Locations (2)
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States