Cybrexa Therapeutics has announced the dosing of the first patient in its Phase 2 clinical trial evaluating CBX-12 in patients with platinum-resistant or refractory ovarian cancer. CBX-12 is a first-in-class peptide-drug conjugate (PDC) designed to selectively deliver exatecan, a potent topoisomerase 1 (TOP1) inhibitor, directly to tumor cells using Cybrexa’s proprietary alphalex™ technology. The trial aims to assess the safety, tolerability, and efficacy of CBX-12 in this patient population, addressing a critical unmet need in ovarian cancer treatment.
The Phase 2 trial is a randomized, open-label study that will evaluate two different doses of CBX-12: 125 mg/m2 and 100 mg/m2, both administered every 21 days. The primary target patient population is women with platinum-resistant or refractory ovarian cancer who have not previously been treated with TOP1-targeted agents. This study follows positive Phase 1 results, which demonstrated a 40% response rate in TOP1-naïve ovarian cancer patients, along with activity across five other solid tumor types and a manageable safety profile.
CBX-12: A Novel Approach to TOP1 Inhibition
CBX-12 differentiates itself from traditional antibody-drug conjugates (ADCs) by not relying on antigen expression for targeting. Instead, it utilizes a pH-low insertion peptide (pHLIP®) to selectively deliver its payload into the cytoplasm of cancer cells. This approach may broaden its utility to patients ineligible for antigen-targeted therapies. The Phase 1 study results, recently presented at the European Society for Medical Oncology Congress (ESMO 2024), highlighted the drug's promising activity across a range of advanced or metastatic solid tumors.
"Dosing the first patient marks an important milestone for the Phase 2 clinical trial in ovarian cancer and for patients facing this aggressive disease," said Per Hellsund, President and Chief Executive Officer of Cybrexa. "CBX-12 recently demonstrated significant antitumor activity, broad application potential, and a favorable safety profile in a Phase 1 study, including encouraging response rates in TOP1-naïve ovarian and breast cancer patients. We are particularly excited about the potential for CBX-12 not only as a standalone treatment but also as a promising candidate for future combination therapies and look forward to its continued advancement in this and additional Phase 2 studies in solid tumors, which are planned for 2025."
Expanding Clinical Development
Cybrexa is planning an additional Phase 2 study of CBX-12 in colorectal cancer in 2025, in collaboration with the National Cancer Institute (NCI). The company also intends to initiate other Phase 2 studies to evaluate CBX-12 as a monotherapy and in combination across a range of solid tumors. Furthermore, Cybrexa is advancing its broader pipeline, including CBX-15, which is expected to enter the clinic in 2025 for the treatment of solid tumors using MMAE (monomethyl auristatin E) as its payload.
About the alphalex™ Technology
The alphalex™ technology is a novel antigen-independent, peptide-drug conjugate platform that enables targeted delivery of highly potent anti-cancer treatments. It consists of a pH-Low Insertion Peptide (pHLIP®), a linker, and a small molecule anti-cancer agent. This platform aims to revolutionize the standard of care in oncology by enhancing the delivery of cancer therapeutics while limiting off-target effects.
