Abstract 648P
Background
CBP-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.
Methods
In 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.
Results
By 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.
Conclusions
CBP-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 identification
NCT05830097.
Editorial acknowledgement
Legal entity responsible for the study
Coherent Biopharma.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
662P - A phase I study evaluating IMM2520 (CD47/PD-L1 bispecific molecule) in pts with advanced solid tumor
Presenter: Yuping Sun
Session: Poster session 01
663P - First-in-human, phase I/II, monotherapy, dose-escalation study of mRNA-4359, an mRNA-encoded PD-L1/IDO1 antigen-specific therapy, in advanced/refractory solid tumors
Presenter: Muhammad Khattak
Session: Poster session 01
664P - Impact of treatment beyond progression (TBP) in patients treated with immunotherapy (IO) in phase I trials (Ph1)
Presenter: Maria Julia Lostes Bardaji
Session: Poster session 01
665P - Safety, PK, immune activation, and clinical outcomes with RBS2418 treatment, an oral ENPP1 inhibitor, alone or in combination with pembrolizumab in advanced solid tumors
Presenter: Thomas Marron
Session: Poster session 01
Resources:
Abstract
666P - Final results of phase I/II study of NUC-7738 as monotherapy and in combination with pembrolizumab: Anti-tumor immune response in PD-1 inhibitor-resistant patients
Presenter: Sarah Blagden
Session: Poster session 01
667P - Phase I study to assess biodistribution of CB307, a trispecific Humabody targeting CD137, prostate-specific membrane antigen, and human serum albumin with 89Zr-CB307 PET
Presenter: Daan Geert Knapen
Session: Poster session 01
668P - First-in-human phase I dose escalation study of ALG.APV-527, a 5T4 tumor antigen-conditional 4-1BB bispecific antibody, in patients with advanced solid tumors, demonstrates positive safety, signals of biological activity and patients with lasting stable disease
Presenter: Thomas Marron
Session: Poster session 01
669P - CBX-12-101: Final results of a phase I study of CBX-12, a peptide drug conjugate (PDC) in patients (pts) with metastatic solid tumors
Presenter: Patricia Lorusso
Session: Poster session 01
670P - Phase I trial of the delta-like ligand-3 (DLL3)/CD3 IgG-Like T cell engager BI 764532 in patients (pts) with DLL3-positive tumors: Updated data
Presenter: Martin Wermke
Session: Poster session 01
671P - LuMIERE: A phase I/II study evaluating safety, dosimetry, and preliminary activity of [177Lu]Lu-FAP-2286 in patients with advanced solid tumors
Presenter: Jonathan McConathy
Session: Poster session 01