NCT04205227

ENB003 Plus Pembrolizumab Phase 1b/2a in Solid Tumors

A Phase 1/2A Trial of ENB 003 in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 137 (estimated)
• Sponsor: ENB Therapeutics, Inc · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

First-in Human study evaluating the safety, tolerability and efficacy of ENB003 in combination with Pembrolizumab in solid tumors. The study is separated into two parts. Part A is a 3+3 dose escalation to define the recommended RP2D; this part will include metastatic melanoma, platinum resistant ovarian cancer, and pancreatic cancer patients subjects, but other solid tumors will be allowed. Once the RP2D is selected, the study will be expanded into metastatic melanoma, platinum resistant ovarian cancer, and pancreatic cancer subjects. A small number of sarcoma subjects will be included, as exploratory.

Detailed description

Part A: Dose Escalation (with Run-in) A 7-day run-in period of ENB-003 monotherapy, will be administered to all Part A subjects on Days -7, -5 and -3, prior to initiating combination therapy with pembrolizumab at Day 1. ENB-003 will also be administered on Days 1, 3 and 5 in Cycle 1. In subsequent cycles, ENB-003 will be administered on Days 1, 3, 5, 8, 10, and 12 of alternate 21-day treatment cycles, starting with Cycle 3. Dose escalation will follow a standard 3+3 design, with the following doses being administered during Part A: * 150 µg ENB-003 * 300 µg ENB-003 * 500 µg ENB-003 * 750 µg ENB-003 * 1000 µg ENB-003 and 2000 µg ENB-003. For 2000 µg doses and above, ENB003 will be administered every 21 day cycle. Pembrolizumab will be administered as 200 mg on Day 1 of each 21-day cycle in all Part A cohorts. Part B: Dose Expansion Twelve (12) subjects with malignant melanoma, ovarian cancer, or pancreatic cancer will receive 1 x 21-day treatment cycle of ENB-003 at the recommended phase 2 dose (RP2D) selected in Part A + pembrolizumab. If dose limiting toxicities (DLT) occur in no more than 3 subjects , Part B will be expanded with an additional 27 subjects, plus 6 additional subjects with sarcoma. A review of efficacy will be conducted by a Data Safety Monitoring Board (DSMB) in Part B once 39 RP2D subjects (including 9 malignant melanoma subjects, 16 ovarian cancer subjects and 14 pancreatic cancer subjects) have completed their scheduled 12 week CT/MRI scans. Upon approval by the DSMB, a maximum of 64 further subjects will be treated at the RP2D.

Conditions

• Cancer
• Melanoma
• Ovary Cancer
• Pancreatic Cancer
• Solid Tumor

Interventions

Type	Name	Description
DRUG	ENB003	ENB003 is selective Endothelin B Receptor Antagonist
DRUG	Pembrolizumab	anti-PD1

Timeline

• Start date: 2020-02-18
• Primary completion: 2026-01-01
• Completion: 2026-03-31
• First posted: 2019-12-19
• Last updated: 2024-09-19

Locations

5 sites across 2 countries: United States, Australia

Regulatory

• FDA-regulated drug study