787P - First-in-human, phase I study of CBP-1008, a first-in-class bi-specific ligand drug conjugate (Bi-XDC), in patients with advanced solid tumors

Background

CBP-1008, a first-in-class Bi-XDC, targets folate receptor α (FRα) and vanilloid subfamily member 6 of transient receptor potential channels (TRPV6) carrying monomethyl auristatin E (MMAE) as the payload. FRα and TRPV6 are highly expressed in various solid tumors, including ovarian cancer (OC).

Methods

The phase 1 study comprised two parts: dose escalation (Phase Ia) and dose expansion (Phase Ib). In Phase Ia, an accelerated titration approach was used for the initial two dose levels (0.015,0.03 mg/kg), followed by a standard “3+3 design” for the remaining 6 doses (0.12-0.20 mg/kg, Q2W). Phase Ib includes platinum-resistant high-grade serous ovarian cancer (HGSOC), clear cell ovarian cancer (OCCC), metastatic triple negative breast cancer (TNBC) and other solid tumors. The primary objective is to assess safety and efficacy.

Results

As of Apr 16, 2024, 268 patients(pts) have been enrolled (41 Phase Ia and 227 Phase Ib; 160 HGSOC,20 OCCC, 25 TNBC and 63 others). Majority of adverse events were mild to moderate without significant eye toxicity (2.6%) and peripheral neuropathy (9.0%) often seen in ADCs with MMAE payload. Common treatment-related AEs (TRAEs) included neutropenia, leukopenia, AST and ALT increased, pyrexia and nausea. Grade 3/4 TRAEs(≥5%) included neutropenia(49.6%), leukopenia(27.2%), AST increased (6.0%), ALT increased (5.6%). At 0.15mg/kg dose, among 31 HGSOC pts who received prior 1-2 lines of taxane-included treatments (if 2 prior lines, ≥12m of time interval between 2 lines; and ≥3m of time interval from the last taxane treatment to CBP-1008 first dose), the objective response rate (ORR) was 48.4% (15 PR) and the disease control rate was 83.9%, regardless of FRα/TRPV6 expression levels. In 16 OCCC pts (0.15mg/kg: n=7; 0.17mg/kg: n=9) the overall ORR was 31.3% (5 PR).

Conclusions

CBP-1008 demonstrated a good safety profile and promising anti-tumor activity in OC, especially OCCC pts, a rare population with lack of effective treatment. It has the potential to be a superior treatment option for OC, regardless of FRα/TRPV6 expression levels. Ning Li, Jifang Gong, Jian Zhang and Dan Liu contributed equally to this work. Lin Shen, Lingying Wu and Xichun Hu are the corresponding authors.

Clinical trial identification

NCT04740398.

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.