CBX-12, a first-in-class peptide-drug conjugate, was given to the first patient in an ovarian cancer clinical trial.
The first patient has been dosed in a trial assessing the peptide-drug conjugate CBX-12 in patients with platinum-resistant or refractory ovarian cancer, according to a press release from Cybrexa Therapeutics, the drug’s manufacturer.
CBX-12 is a first-in-class peptide-drug conjugate that delivers exatecan, a TOP1 inhibitor, to tumor cells, according to the release. This particular peptide-drug conjugate may potentially be used in patients who may not be eligible for antigen-targeted therapies like antibody-drug conjugates and monoclonal antibodies.
In a prospective study published in the Journal of Medicinal Chemistry in January 2024, authors noted that peptide-drug conjugates are similar to antibody-drug conjugates for its multifactor therapeutic mechanism, but the one characteristic that may make it stand out is its less severe off-target side effects and greater size specificity.
“Dosing the first patient marks an important milestone for the phase 2 clinical trial in ovarian cancer and for patients facing this aggressive disease,” Per Hellsund, President and Chief Executive Officer of Cybrexa, said in the release. “CBX-12 recently demonstrated significant antitumor activity, board application potential and a favorable safety profile in a phase 1 study, including encouraging response rates in TOP1-naïve ovarian and breast cancer patients.”
In this phase 2 trial, researchers are evaluating the tolerability, safety and efficacy of CBX-12 in women with platinum-resistant or refractory ovarian cancer at two different doses: 125 milligrams per square meter (mg/m2) or 100 mg/m2, both of which are administered every 21 days. Treatment in the study will continue until disease progression or unacceptable toxicity.
According to the study’s ClinicalTrials.gov listing, researchers conducting this phase 2 study will focus on several outcomes including objective response rate (the percentage of patients with a complete or partial response to treatment), treatment-emergent side effects, median duration of response and progression-free survival (defined as the time from treatment assignment to first evidence of disease progression or all-cause death). Pharmacokinetics (ways the drug is absorbed or processed in the body) will also be assessed throughout the study.
Researchers aim to enroll an estimated 60 patients in this study, according to ClinicalTrials.gov. The study completion date is aimed at July 2026.
The initiation of this phase 2 trial follows findings from a phase 1 trial presented at the 2024 ESMO Congress, which demonstrated activity across several cancers including breast, ovarian, non-small cell lung cancer, gallbladder, thymic and colorectal cancers. In the recently presented results of 69 patients, the overall response rate was 36% in patients with ovarian cancer, 19% in those with breast cancer, 14% in patients with colorectal cancer and 50% in those with non-small cell lung cancer.
The most common grade 3-4 (severe or life-threatening) side effects reported in the phase 1 study included anemia (24.6%), leukopenia (decreased leukocyte count, a type of white blood cell; 21.7%), neutropenia (decreased neutrophil count, a type of white blood cell; 27.5%) and thrombocytopenia (decreased platelets in blood, which may result in excessive bleeding or easy bruising; 13%). In the poster presented at the oncology conference, researchers noted that “CBX-12 had a manageable safety profile, which is amenable to future combinations.”
The press release noted that other studies are planned in 2025 to assess the peptide-drug conjugate in patients with colorectal cancer.
“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,” Hellsund said in the release.
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