An open-label, MRCT phase I/II study evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy of first-in-class bi-ligand-drug conjugate CBP-1019 in patients (pts) with advanced solid tumors

BackgroundCBP-1019 is a globally first-in-class bi-specific ligand drug conjugate (Bi-XDC) that targets both FRα and TRPV6 with the payload of exatecan (DX-8951), developed by Coherent Biopharma. Preclinical studies have shown that CBP-1019 with a MW of only 3 KD can deliver more payloads than TOPO-I ADCs with a favorable safety profile, demonstrating a therapeutic window of 15-30 folds greater. Up to 90%-100% TGI was observed in PDX models at the dose of 50-75 mg/kg (equivalent to 4 - 6 mg/kg in human). We designed a phase I/II study to evaluate the safety and efficacy of CBP-1019 in pts with advanced solid tumors (NCT05830097). Currently, we reported the results from the phase I study.MethodsIn phase I study, an accelerated titration design was employed for the first two dose levels (1.0, 2.0 mg/kg Q2W), followed by a standard "3+3� design for the subsequent dose levels (3.0 - 6.0 mg/kg Q2W). Dose expansion would be conducted in selected dose levels. The primary endpoints included safety, MTD, RP2D and ORR.ResultsBy 31st Mar. 2024, 22 pts were enrolled (1.0 - 4.0 mg/kg), with median age of 59 years. All pts were heavily prior treated with median 4 lines of treatment. DLT was not observed and MTD not yet reached. Most TRAEs were grade 1 or 2. The most commonly ≥grade 3 TRAEs mainly in neutrophil count decreased (27.3%), platelet count decreased (18.2%), white blood cell count decreased (13.6%), anemia (9.1%) and lymphocyte count decreased (9.1%). 4 pts have been treated for over 4 months (the longest treatment duration is over 7 months) without AEs of interstitial pneumonia or ophthalmic toxicity occurred. Among 13 efficacy evaluable pts ≥ 2.0 mg/kg dose, 2 ovarian cancer pts with confirmed PR (maximum target lesion reduction was 66.0% and 34.0%, respectively) and 9 with SD were observed. The exposure of CBP-1019 and DX-8951 increased with dose escalation, without accumulation of either substance after multiple doses.ConclusionsCBP-1019 as the first-in-class bi-XDC globally, was well-tolerated at 1.0 - 4.0 mg/kg Q2W without DLTs or other common severe toxicities observed in ADCs. Preliminary antitumor activity was seen at ≥2 mg/kg dose.Clinical trial identificationNCT05830097.Legal entity responsible for the studyCoherent Biopharma.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.