On November 7, 2023 ENB Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on oncology and immunology, reported top-line results from the dual combination arm of the Phase 1b ENBOLDEN-101 study, evaluating ENB-003 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with advanced refractory cancers (Press release, ENB Therapeutics, NOV 7, 2023, View Source [SID1234637201]). The results show encouraging objective responses, disease control and extended progression-free survival in patients with platinum resistant/ refractory ovarian cancer (PROC). The poster, entitled, "ENB-003, an ETBR antagonist, in combination with pembrolizumab, shows promise in microsatellite stable platinum refractory/resistant ovarian cancer: Data from the ENBOLDEN-101 Phase 1B study" was presented on November 3, 2023 at a poster session at the SITC (Free SITC Whitepaper) 2023 meeting, was held November 1-5, in San Diego, California, USA.

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The data included 5 patients with metastatic microsatellite stable (MSS) PROC who had disease progression after one or more previous lines of treatment. Study treatment consisted of an initial 7-day run-in period of ENB-003 monotherapy, followed by repeated 3-week cycles of ENB-003 in combination with KEYTRUDA.

The data demonstrated that the treatment regimen was safe and well tolerated. The objective response rate (ORR) and disease control rate (DCR- patients exhibiting a response or stable disease) in MSS PROC was 40% and 80% respectively (N=5), including 2 patients with partial responses showing a 95% and 33% reduction in tumor burden respectively, as well as 4 patients with stable disease; 80% of PROC patients demonstrated shrinkage of target lesions overall. The 8-month progression-free survival rate was 60%. This compares favorably with a historical ~20% progression-free survival data at 6 months for single agent anti-PD1 and an ~8% ORR and an ~22% DCR.

"These data, demonstrate that ENB-003 in combination with KEYTRUDA is safe, with encouraging signs of clinical activity and support the combination’s potential to become an effective immunotherapy regimen for MSS primary PROC – a disease that has responded very poorly to available treatments," stated Sumayah Jamal, MD-Ph.D., President, Chief Scientific Officer, and Co-Founder of ENB Therapeutics. "We are extremely pleased with the top-line results from this ongoing study. We look forward to continuing our collaboration with Merck and anticipate initiating Part 2 of the study next year." For more information on this Phase 1/2a study, see NCT04205227.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About ENB-003

ENB-003 is a selective endothelin B receptor (ETBR) inhibitor that, in preclinical studies, enhances efficacy of CAR-T and anti-PD-1 in solid tumors across multiple cancer types in preclinical studies. In an ongoing multi-center Phase 1/2 clinical trial, early efficacy signals suggest that ENB-003 overcomes resistance to pembrolizumab in heavily pre-treated drug resistant cancer patients. The Phase 2 portion of the ENB-003 + pembrolizumab combination study is expected to start in the first half of 2024. The trial will enroll MSS primary PROC, as well as MSS pancreatic cancer patients and patients with other advanced solid tumors that have failed standard of care.