In a first-in-human trial, a peptide-drug conjugate showed tolerability and antitumor activity in patients with advanced solid tumors.
CBX-12, a peptide-drug conjugate (PDC), showed tolerability and antitumor activity as a single agent in patients with advanced or metastatic solid tumors in a report presented at the EORTC-NCI-AACR Symposium.1
Investigators in the first-in-human phase 1/2 CBX-12-101 study (NCT04902872) successfully treated 24 patients with CBX-12 with manageable rates of adverse events (AEs) and observed 1 complete response (CR) and 1 partial response (PR) from 18 evaluable patients, according to a press release from Cybrexa Therapeutics.1,2
“In this phase 1 study, CBX-12 demonstrated safety and tolerability, without significant gastrointestinal toxicity. We also saw signal of antitumor activity in multiple tumor types,” stated principal investigator Funda Meric-Bernstam, MD, chair of the department of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, in a press release.1
CBX-12 is an alphalex™ PDC that consists of a low-pH insertion peptide, a self-immolating linker, and the potent topoisomerase I inhibitor exatecan. Unlike an antibody-drug conjugate, it is designed to target tumors without requiring a certain antigen. Instead, it activates in an acidic tumor microenvironment and links to the tumor cell membrane.
The study enrolled patients with solid tumors whose disease has no approved regimen with a proven survival advantage, including patients with ovarian, testicular, breast, colorectal, gastric, and small cell lung cancer (SCLC). In the phase 1 portion, patients received escalating doses of CBX-12 on 3 schedules: 5 times daily every 3 weeks, 3 times daily every 3 weeks, and once weekly.2
The primary end points were safety, tolerability, and maximum tolerated dose or recommended phase 2 dose (RP2D). Secondary and exploratory end points included antitumor activity per RECIST v1.1, measurement of anti-drug antibodies, and evaluation of plasma pharmacokinetics and intratumoral levels of CBX-12 and exatecan.
The single CR was reported in a patient with ovarian cancer, and the PR in a patient with breast cancer. There were 13 other treated patients with stable disease.1
The most common treatment-related AEs included 11 patients with nausea, 8 patients each reporting diarrhea, vomiting, and anemia, decreased white blood cell (WBC) and absolute neutrophil count (ANC) in 7 patients, fatigue in 7 patients, dehydration in 4 patients, increased aspartate transferase in 3 patients, and alopecia in 3 patients. Grade 3 ANC decrease was seen in 2 patients while grade 4 was seen in 3 patients. There were 4 incidences of grade 3 anemia and 3 cases of grade 4 decrease in platelets. Grade 3 WBC decreases were seen in 1 patient and grade 4 in 2 patients. Dose-limiting toxicities included decreased ANC and platelets, febrile neutropenia, and sepsis.
The preliminary RP2D in the 3 times daily every 3 weeks cohort was 45 mg/m2. Phase 2 expansion cohorts are planned for patients with ovarian cancer and SCLC.
“This study’s data provides us with important early signs of clinical viability of Cybrexa’s alphalex technology platform, which opens the door for us to move forward rapidly with the development of our pipeline,” said Arthur DeCillis, MD, chief medical officer of Cybrexa Therapeutics, in a statement.1
1. Cybrexa Therapeutics presents findings from first-in-human study of CBX-12 as a plenary oral presentation at 34th EORTC-NCI-AACR Symposium. Cybrexa Therapeutics. October 28, 2022. Accessed October 31, 2022. https://yhoo.it/3UdC2kl
2. Meric-Bernstam F, Eder JP, Vandross A, et al. CBX-12-101: A first-in-human study of CBX-12, an alphalex peptide drug conjugate (PDC) in patients with advanced or metastatic solid tumors. Eur J Cancer. 2022;174(suppl_1):S7-S8. doi:10.1016/S0959-8049(22)00823-1