Findings from a phase 1 trial shows the early promise of an ENB-003 and pembrolizumab regimen for the treatment of platinum refractory or resistant ovarian cancer.
ENB-003, an endothelin receptor B (ETBR) antagonist, shows potential in combination with pembrolizumab (Keytruda) for the treatment of metastatic microsatellite-stable (MMS) platinum refractory or resistant ovarian cancer (PROC), according to findings presented at the Society for the Immunotherapy of Cancer Annual Meeting, held November 1-5.1
Across 5 patients with MMS PROC who had disease progression after 1 or more prior lines of treatment, the objective response rate (ORR) was 40% and the disease control rate (DCR) was 80%. Two patients with partial responses showed 95% and 33% reductions in tumor burden, respectively, and 4 patients displayed stable disease. Additionally, target lesion shrinkage was observed in 80% of patients with PROC.
Moreover, progression-free survival (PFS) at 8 months was 60%, compared with a historical PFS of approximately 20% at 6 months with single-agent anti-PD1, according to ENB Therapeutics.
"These data demonstrate that ENB-003 in combination with [pembrolizumab] 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, PhD, president, chief scientific officer, and co-founder of ENB Therapeutics, in a press release.1
The phase 1b ENBOLDEN-101 study (NCT04205227) is investigating ENB-003 in combination with pembrolizumab in patients with advanced refractory cancers.2 The first-in-human study is evaluating the regimen’s safety, tolerability, and efficacy.2
Part A is a 3+3 dose-escalation phase to determine the recommended phase 2 dose (RP2D). The primary end point of part A is incidence of treatment-emergent adverse events.
Part B is a dose-expansion phase. The primary end points of part B are ORR and overall survival (OS). The part B secondary end points are PFS, duration of response, time to progression, OS, pharmacokinetics, and immunohistochemistry assessment of ETBR PD-L1.
The study treatment started with a 7-day run-in period of ENB-003 monotherapy. This was followed by 3-week cycles of ENB-003 and pembrolizumab.
Along with ovarian cancer, the trial also enrolled patients with malignant melanoma, pancreatic cancer, head and neck squamous cell carcinoma, and triple-negative breast cancer. Patients with all tumor types needed to have a life expectancy of >3 months and an ECOG performance status of 0 or 1, and women could not be post-menopausal.
Earlier this year, 2 phase 3 trials failed to show improvements in survival for PROC.The phase 3 AXLerate-OC trial (NCT04300140) of batiraxcept and paclitaxel missed its primary end point of PFS, and the phase 3 ENGOT-ov50/GOG-3029/INNOVATE-3 trial(NCT03940196) of tumor-treating fields and paclitaxel missed its primary end point of OS. More recently, however, findings from the phase 3 MARISOL trial (NCT04209855) demonstrated improvements in folate receptor alpha-positive PROC with mirvetuximab soravtansine-gynx (Elahere).