1602P - CBP-1018, Bi-ligand-drug conjugate (Bi-XDC) drug treated for metastatic castration resistant prostate cancer (mCRPC) patients from phase I study results

Background

CBP-1018 is a first-in-class bi-ligand-drug conjugate targeting both PSMA and FRα with monomethyl auristatin E (MMAE) as the payload. Preclinical studies have shown that CBP-1018 with a MW of only 3 KD can deliver more payloads than MMAE ADCs with a favorable safety profile. In the Phase I study (NCT04928612), CBP-1018 had showed well-tolerated safety profiles and preliminary anti-tumor activity in patients (pts) with advanced solid tumors.

Methods

This ongoing Phase I study consists of several stages. The design of the dose escalation stage is an accelerated titration at 0.03 mg/kg Q2W following by a standard “3+3” from 0.06 to 0.16 mg/kg. The dose expansion stage is conducted at selected dose levels. The primary endpoints are safety, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), objective response rate (ORR) and PFS.

Results

By 9^th Mar, 2024, a total of 93 pts were enrolled (21 pts for dose escalation, and 72 pts for dose expansion at 0.12, 0.14 and 0.16 mg/kg). 97.8% of the pts had mCRPC. No DLT was observed and the MTD was not yet reached. The median age was 69 (range:50-78). The median number of prior treatments was 7 (68.8% pts with prior chemotherapy). Most treatment-related adverse events (TRAEs) were grade 1 or 2. Grade ≥3 TRAEs mainly included neutrophil count decreased (44.1%), WBC count decreased (20.4%), hypokalaemia (15.1%). No ocular toxicity was observed. There were only 4 (4.3%) pts experienced TRAE leading to dose reduction without any TRAE leading to death. Among all mCRPC pts with target lesions, dose levels ≥0.14 mg/kg show better efficacy: 20% ORR and 80% DCR based on RECIST v1.1 in 15 efficacy evaluable pts with target lesions in ≥0.14 mg/kg dose levels. And the median radiographic progression-free survival (rPFS) was 7 months and over 40% of them experienced PSA decreased. The exposure of CBP-1018 and free MMAE increased with dose escalation.

Conclusions

CBP-1018, as the first bi-XDC globally, has showed a promising preliminary efficacy and well-tolerated safety profile in mCRPC pts, supporting a further investigation in mCRPC pts to decide optimal dose and further confirmation in a large scale population. Yehui Shi and Hai Huang are the corresponding authors.

Clinical trial identification

NCT04928612.

Editorial acknowledgement

Legal entity responsible for the study

Coherent Biopharma.

Funding

Has not received any funding.

Disclosure

R. Huang, M. Xu, B. Pan, J. Zhang: Financial Interests, Personal, Full or part-time Employment: Coherent Biopharma. All other authors have declared no conflicts of interest.