A Study to Evaluate the Safety and Tolerability of ETC-1922159 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumours
- Conditions
- Solid Tumors
- Interventions
- Registration Number
- NCT02521844
- Lead Sponsor
- EDDC (Experimental Drug Development Centre), A*STAR Research Entities
- Brief Summary
This is a Phase 1A/B study consisting of four parts.
1. Part A (completed) is a non-randomised, open-label, sequential evaluation of the safety, pharmacokinetics (PK), maximum tolerated dose (MTD), and recommended dose (RD) of ETC-1922159 in patients with advanced or metastatic, or unresectable solid malignancies, for whom no approved treatment option or standard of care is available. Dose escalation, with the goal of identifying the MTD and RD, is guided by an ordinal continual reassessment method (oCRM) model with a cohort size of one patient.
2. Part A extension (completed) is a non-randomised, non-comparative, open-label evaluation of the safety and tolerability of ETC-1922159 together with the bone protective treatment (denosumab) in patients with advanced or metastatic, or unresectable solid malignancies, for whom no approved treatment option or standard of care is available.
3. Part B dose escalation (completed) is a non-randomised, open-label, sequential evaluation of the MTD, RD, safety, PK, and PD (pharmacodynamics) of ETC 1922159 in combination with pembrolizumab in patients with advanced or metastatic, or unresectable solid malignancies, for whom no approved treatment option or standard of care is available.
4. Part B dose expansion will be a non-randomised, non-comparative, open-label study evaluation of the safety and tolerability of ETC-1922159 as a single agent until disease progression and then in combination with pembrolizumab at the RD identified in the Part B dose escalation segment, in patients with advanced or metastatic, or unresectable solid malignancies that are refractory, intolerant or not suitable for available treatment according to the treating physician.
It is anticipated that the study will take approximately 78 months to complete (36 months for Part A and Part A Extension, approximately 6 months for Part B dose escalation and approximately 36 months for Part B dose expansion).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 89
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation Pembrolizumab ETC-1922159 + pembrolizumab Dose Expansion Pembrolizumab ETC-1922159 as single agent until disease progression, then in combination with pembrolizumab at the recommended dose (RD) identified in the dose escalation segment Dose Escalation ETC-1922159 ETC-1922159 + pembrolizumab Dose Expansion ETC-1922159 ETC-1922159 as single agent until disease progression, then in combination with pembrolizumab at the recommended dose (RD) identified in the dose escalation segment
- Primary Outcome Measures
Name Time Method Number of participants with abnormal 12-lead electrocardiogram (ECG) readings (Part B Dose Expansion) From date of enrolment until end of treatment Maximum Tolerated Dose (MTD) of ETC-1922159 when administered with pembrolizumab (Part B Dose Escalation) For 2 cycles (42 days) Recommended Dose (RD) of ETC-1922159 when administered with pembrolizumab (Part B Dose Escalation) For 2 cycles (42 days) Change in Eastern Cooperative Oncology Group performance status (Part B Dose Expansion) From date of enrolment until end of treatment Number of participants with abnormal clinical laboratory test results (Part B Dose Expansion) From date of enrolment until end of treatment Number of participants with adverse events (AEs) (Part B Dose Expansion) From date of enrolment until end of treatment Number of participants with abnormal vital sign measurements (Part B Dose Expansion) From date of enrolment until end of treatment Number of participants with adverse bone density imaging assessments via DEXA scan (Part B Dose Expansion) From date of enrolment until end of treatment Tolerability measured by monitoring of fatigue and gastrointestinal-related side effects and when applicable, immune-related side effects in patients (Part B Dose Expansion) From date of enrolment until end of treatment
- Secondary Outcome Measures
Name Time Method Number of participants with adverse bone density imaging assessments via DEXA scan (Part B Dose Escalation) From date of enrolment until end of treatment Number of participants with abnormal 12-lead electrocardiogram (ECG) readings (Part B Dose Escalation) From date of enrolment until end of treatment Number of participants with abnormal vital sign measurements (Part B Dose Escalation) From date of enrolment until end of treatment Number of participants with adverse events (AEs) (Part B Dose Escalation) From date of enrolment until end of treatment Change in Eastern Cooperative Oncology Group performance status (Part B Dose Escalation) From date of enrolment until end of treatment Tolerability measured by monitoring of fatigue and gastrointestinal-related side effects and when applicable, immune-related side effects in patients (Part B Dose Escalation) From date of enrolment until end of treatment Clinical activity measured by RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 and iRECIST (Response Evaluation Criteria in Solid Tumours modified for immune-based therapeutics) (Part B Dose Expansion) From date of enrolment until end of treatment Retrospective evaluation of plasma/serum concentration of bone protective agents, if administered (Part B) Before and after the first administration only Number of participants with abnormal clinical laboratory test results (Part B Dose Escalation) From date of enrolment until end of treatment Clinical activity measured by RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 and iRECIST (Response Evaluation Criteria in Solid Tumours modified for immune-based therapeutics) (Part B Dose Escalation) From date of enrolment until end of treatment ETC-1922159 Maximum plasma concentration (Cmax) (Part B) From date of enrolment until end of treatment ETC-1922159 Area under the curve (AUC) (Part B) From date of enrolment until end of treatment Retrospective evaluation of plasma/serum concentration of pembrolizumab (Part B) From date of enrolment to Cycle 2 for Dose Escalation and Cycle 1 of combination therapy for Dose Expansion
Trial Locations
- Locations (11)
University of Arizona Cancer Center, 3838 N. Campbell Avenue, RM 2111, Site 203
🇺🇸Tucson, Arizona, United States
National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 7, Site 101
🇸🇬Singapore, Singapore
National Cancer Centre Singapore, 11 Hospital Drive, Site 102
🇸🇬Singapore, Singapore
University of Kansas Medical Center, 4350 Shawnee Mission Parkway, Suite 2310, MS 6004, Site 210
🇺🇸Fairway, Kansas, United States
Chao Family Comprehensive Cancer Center,Stern Center for Cancer Clinical Trials and Research, 101 City Drive South, Site 209
🇺🇸Orange, California, United States
Duke University Medical Center, Duke Cancer Center, 20 Duke Medicine Circle, Site 206
🇺🇸Durham, North Carolina, United States
Washington University School of Medicine, Siteman Cancer Center, 4921 Parkview Place, Site 205
🇺🇸Saint Louis, Missouri, United States
University of Colorado Hospital Anschutz Cancer Pavilion, 12648 East 17th Avenue; MSF 700, Site 202
🇺🇸Aurora, Colorado, United States
Oregon Health and Science University-Knight Cancer Institute, 3485 S Bond Ave., Mail code 0C14CTSite 211
🇺🇸Portland, Oregon, United States
Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Mail Code Cr 9-4, Site 211
🇺🇸Portland, Oregon, United States
Department of Investigational Cancer Therapeutics, 1400 Holcombe Blvd., Unit 455, Site 201
🇺🇸Houston, Texas, United States