A Phase 1b/2, Open-label, Multicenter, Dose-escalation and Expansion Trial of Intratumoral SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (SYNERGY-001)
Overview
- Phase
- Phase 1
- Intervention
- SD-101(1)
- Conditions
- Metastatic Melanoma
- Sponsor
- Dynavax Technologies Corporation
- Enrollment
- 241
- Locations
- 47
- Primary Endpoint
- Phase 1 Dose Escalation and Phase 2 Dose Expansion - Overall Response Rate (ORR) by Analysis Group
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a phase 1b/2, open-label, multicenter trial designed to evaluate the safety, tolerability, biologic activity, and preliminary efficacy of intratumoral SD-101 injections in combination with intravenous pembrolizumab in patients with metastatic melanoma or recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
This study will be conducted in 2 phases. Phase 1 evaluates SD-101 given in combination with pembrolizumab in melanoma populations (anti-PD-1/L1 naïve and anti-PD-1/L1 experienced with progressive disease) in up to 4 Dose Escalation cohorts to identify a recommended Phase 2 dose (RP2D) to be evaluated in up to 4 Dose Expansion cohorts in Phase 2. Phase 2 also includes up to 4 Dose Expansion cohorts of patients with HNSCC (anti-PD-1/L1 naïve and anti-PD-1/L1 experienced with progressive disease).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Dose Escalation Phase 1b
Determine the maximum tolerated dose (MTD) of escalating doses of SD-101(1) administered in combination with pembrolizumab in patients with melanoma (anti-PD-1/L1 therapy naïve and experienced patients with progressive disease).
Intervention: SD-101(1)
Dose Escalation Phase 1b
Determine the maximum tolerated dose (MTD) of escalating doses of SD-101(1) administered in combination with pembrolizumab in patients with melanoma (anti-PD-1/L1 therapy naïve and experienced patients with progressive disease).
Intervention: Pembrolizumab
Dose Expansion Phase 2 (Cohort 1)
Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent or metastatic melanoma.
Intervention: SD-101(2)
Dose Expansion Phase 2 (Cohort 1)
Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent or metastatic melanoma.
Intervention: Pembrolizumab
Dose Expansion Phase 2 (Cohort 2)
Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy progressing patients with recurrent or metastatic melanoma.
Intervention: SD-101(2)
Dose Expansion Phase 2 (Cohort 2)
Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy progressing patients with recurrent or metastatic melanoma.
Intervention: Pembrolizumab
Dose Expansion Phase 2 (Cohort 3)
Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent head and neck squamous cell carcinoma.
Intervention: SD-101(2)
Dose Expansion Phase 2 (Cohort 3)
Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent head and neck squamous cell carcinoma.
Intervention: Pembrolizumab
Dose Expansion Phase 2 (Cohort 4)
Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy progressing patients with recurrent head and neck squamous cell carcinoma.
Intervention: SD-101(2)
Dose Expansion Phase 2 (Cohort 4)
Determine the safety and efficacy of SD-101(2) and pembrolizumab in anti-PD-1/L1 therapy progressing patients with recurrent head and neck squamous cell carcinoma.
Intervention: Pembrolizumab
Dose Expansion Phase 2 (Cohort 5)
Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent or metastatic melanoma.
Intervention: SD-101(3)
Dose Expansion Phase 2 (Cohort 5)
Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent or metastatic melanoma.
Intervention: Pembrolizumab
Dose Expansion Phase 2 (Cohort 6)
Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent head and neck squamous cell carcinoma.
Intervention: SD-101(3)
Dose Expansion Phase 2 (Cohort 6)
Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy naïve patients with recurrent head and neck squamous cell carcinoma.
Intervention: Pembrolizumab
Dose Expansion Phase 2 (Cohort 7)
Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy refractory or resistant patients with recurrent head and neck squamous cell carcinoma.
Intervention: SD-101(3)
Dose Expansion Phase 2 (Cohort 7)
Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy refractory or resistant patients with recurrent head and neck squamous cell carcinoma.
Intervention: Pembrolizumab
Dose Expansion Phase 2 (Cohort 8)
Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy refractory or resistant patients with recurrent or metastatic melanoma.
Intervention: SD-101(3)
Dose Expansion Phase 2 (Cohort 8)
Determine the safety and efficacy of SD-101(3) and pembrolizumab in anti-PD-1/L1 therapy refractory or resistant patients with recurrent or metastatic melanoma.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Phase 1 Dose Escalation and Phase 2 Dose Expansion - Overall Response Rate (ORR) by Analysis Group
Time Frame: Day 1 through Day 743
Overall response rate (ORR) by analysis group based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 was evaluated from Baseline (Day 1) through Day 743 or End of Study (EOS).
Phase 1 Dose Escalation Only - Number of Participants With DLTs
Time Frame: Day 1 through Day 29
Dose-limiting toxicities (DLTs) are defined per protocol as specific AEs occurring from the time of the first injection (Day 1) through Day 29.
Secondary Outcomes
- Phase 1 Dose Escalation and Phase 2 Dose Expansion - Progression-Free Survival Rate by Analysis Group(Day 1 through Day 743)
- Phase 1 Dose Escalation and Phase 2 Dose Expansion - Time to Objective Response by Analysis Group(Day 1 through Day 743)
- Phase 1 Dose Escalation and Phase 2 Dose Expansion - Duration of Response by Analysis Group(Day 1 through Day 743)
- Phase 1 Dose Escalation and Phase 2 Dose Expansion - Disease Control Rate (DCR) by Analysis Group(Day 1 through Day 743)