Updated results from a phase I/II study of CBP-1018, a bi-ligand–drug conjugate (Bi-XDC) as late line therapy for patients with metastatic castration resistant prostate cancer (mCRPC).

161 Background: Patients (Pts) with mCRPC have a poor prognosis with limited treatment options, particularly those who have progressed after novel hormonal agents (NHA) and chemotherapy. CBP-1018 has demonstrated a well-tolerated safety profile based on 112 pts and preliminary efficacy in mCRPC at RP2D of 0.14mg/kg as shown in 2024ASCO and 2024ESMO. Here we report the updated safety data of 120 pts and efficacy at ≥0.14mg/kg including pts treated with prior 2 nd generation androgen receptor pathway inhibitor (ARPI) and taxane from the Phase I/II study. Methods: In this study, pts with progressive mCRPC after standard of care regardless of the number of prior therapies were enrolled. Response evaluation was undertaken per PCWG3 and RECIST v1.1. Primary endpoints were ORR, rPFS and safety. Results: As of cutoff date of 31-Aug 2024, a total of 120 pts were enrolled. 8.3% (10/120) of pts experienced treatment related adverse event (TRAE) leading to dose reduction and 4.2% (5/120) had TRAE leading to discontinuation. The AEs were consistent with the known safety profile, with the most common ≥G3 TRAE primarily being hematologic, which were transient and easily manageable. Typical common AEs seen with ADC were rarely observed; only 1 pt experienced treatment related visual acuity reduction and 11.7% (14/120) of pts experienced peripheral neuropathy. All of these TRAEs were G1. 76 pts were enrolled at ≥0.14mg/kg dose level (0.14mg/kg N=69; 0.16mg/kg N=7). 68.4% (52/76) with ECOG 1. 17.1% (13/76) had liver metastases and 15.8% (12/76) had lung metastases. Additionally, 67.1% (51/76) had received at least one prior taxane and at least one 2 nd generation ARPI, while 53.9% (41/76) had received ≥ 2 prior 2nd generation ARPIs. 21.1% (16/76) had received prior PARP inhibitors. Among 25 pts with target lesion (≥0.14mg/kg), ORR was 20% and DCR was 88.0%. Target lesion reduction was observed in 60% of pts. In the subset of 15 pts with prior taxane and 2 nd generation ARPI treated pts with target lesion (0.14mg/kg), ORR was 20% and DCR was 80%. Among 69 pts (0.14mg/kg), median radiographic progression-free survival (rPFS) has not yet been reached; 7-month rPFS rate was approximately 70%, and 12-month rPFS rate was about 60%. Among the 48 pts with prior taxane and 2 nd generation ARPI treated (0.14mg/kg), 7-month rPFS rate was around 66%. Conclusions: CBP-1018 shows potential as a viable therapeutic option for heavily treated mCRPC pts based on the superior rPFS and anti-tumor activity, warranting further evaluation in later phase III trials. Clinical trial information: NCT04928612 .