Senhwa Biosciences presented clinical data at the 2024 ESMO Congress indicating that Pidnarulex (CX-5461) demonstrates promising efficacy in treating advanced solid tumors harboring BRCA1/2 or PALB2 gene defects. The Phase Ib study, conducted in Canada and the USA, enrolled end-stage oncology patients who had exhausted other treatment options, including PARP inhibitors. The results suggest that Pidnarulex could offer a new therapeutic avenue for patients with limited alternatives.
The open-label, multicenter, multinational study included patients with BRCA2 and/or PALB2 gene deficiencies across various tumor types, such as pancreatic, ovarian, prostate, and breast cancers, as well as ovarian cancer patients with BRCA1 deficiencies and/or other HRD-related homologous recombination defects. The primary objective was to determine the recommended Phase II trial dose, while secondary endpoints focused on evaluating safety, tolerability, and antitumor activity.
Clinical Trial Results
Out of 28 enrolled patients, 22 completed at least one cycle of treatment and were evaluated for dose-limiting toxicity (DLT). The patients had undergone a median of 6 prior lines of therapy (ranging from 2 to 10), with 77% having received platinum-based chemotherapy, 41% bevacizumab, and 86% PARP inhibitors. Among the 15 patients evaluable for drug response, 40% achieved clinical benefit, with stable disease (SD) being the best therapeutic response observed.
Notably, five ovarian cancer patients, including three with BRCA1 somatic mutations, one with a BRCA1 germline mutation, and one with HRD-related gene mutations, achieved stable disease. All five had previously failed platinum chemotherapy and PARP inhibitor treatments, with two maintaining stable disease for at least 6 months following Pidnarulex treatment.
Potential as a Rescue Medication
Currently, several PARP inhibitors are approved for cancers with BRCA1/2 gene deficiencies. Mutations in PALB2 are also critical in triple-negative breast cancer and are associated with higher risks of ovarian and pancreatic cancers. Pidnarulex, a next-generation DDR drug, has the potential to be developed as a rescue medication for patients who have developed resistance to PARP inhibitors. Preclinical studies suggest Pidnarulex can modulate the tumor microenvironment, enhancing the sensitivity and efficacy of immunotherapies like anti-PD-1 and anti-PD-L1. Senhwa anticipates combining Pidnarulex with immunotherapy drugs such as Keytruda to improve treatment outcomes, given that immunotherapy alone has limited efficacy (around 20% of patients experience significant effects). Photosensitivity was found to be manageable through preventive measures.
