689P - DB-1305 (a Trop-2 targeted antibody-drug-conjugate [ADC]) in patients (pts) with advanced solid tumors: Preliminary clinical results from the phase (Ph) I/IIa study

Background

DB-1305 is a novel ADC composed of a humanized anti-trophoblast cell-surface antigen 2 (Trop-2) IgG1 monoclonal antibody attached to a DNA topoisomerase I inhibitor (P1021) via a cleavable linker. Here, we present the initial results of the first-in-human (FIH) study.

Methods

This multi-center, open-label Ph 1/2a study includes dose escalation and expansion. Pts with advanced solid tumors who had failed standard therapy were enrolled. In Ph1, DB-1305 was planned to be administered from 2 mg/kg to 8 mg/kg (Q3W, iv) in a 3+3 design with accelerated titration for the starting dose; additional pts were enrolled to determine the recommended phase 2 dose (RP2D). Ph 2a will enroll approximately 10-40 pts per cohort at the RP2D to assess efficacy.

Results

As of 07 Apr 2023, 44 pts (2 mg/kg, n=1; 4 mg/kg, n=20; 5 mg/kg, n=17; 6 mg/kg, n=6) were enrolled in the Ph1. The median treatment duration was 1.5 (range, 0.7-6.1) months with 25 pts (56.8%) remaining on treatment. Pts had 3 median prior lines of therapy (range, 1-6). Three patients dosed at 6 mg/kg experienced dose-limiting toxicities (i.e., stomatitis, febrile neutropenia, and white blood cell decreased), and the maximum tolerated dose was established as 5 mg/kg. The most common (≥30%) treatment-related adverse event (TRAE) was stomatitis (75.0%). The most common (≥10%) Gr≥3 TRAE was stomatitis (22.7%), while all other events were reported in ≤2 pts. No TRAE led to death. The initial PK results suggest that exposure of DB-1305 increased with dose. The half-life of DB-1305 is approximately 3-4.5 days at the dose range of 4-6 mg/kg. The average systemic ADC/payload molar ratio is approximately 80, indicating ADC stability in systemic circulation. As of cut-off date, 7 pts (non-small cell lung cancer [NSCLC], n=6; fallopian tube cancer, n=1) had partial responses, 4 confirmed, and 3 requiring further confirmation. The objective response rate (ORR) was 30.4% (7/23), and disease control rate (DCR) was 87.0% (20/23). Thirteen NSCLC pts had an ORR of 46.2% (6/13), with a DCR of 92.3% (12/13).

Conclusions

DB-1305 has a manageable toxicity profile. Encouraging efficacy signals were observed in the NSCLC. Study continues to identify dose(s) of DB-1305.

Clinical trial identification

NCT05438329, released on 29 June 2022.

Editorial acknowledgement

Legal entity responsible for the study

Duality Biologics.

Funding

Duality Biologics.

Disclosure

O. Marathe, Y. Cheng, A.I. Spira, E.P. Hamilton, M.M. Rubinstein, X. Dong, L. Li, D. Lv, J. Shi, N. Gabrail, H. Amin, C. Wu, N.T. Ueno: Non-Financial Interests, Institutional, Principal Investigator: Duality Biologics. Z. Zhu, Y. Qiu, V. Gu: Financial Interests, Personal, Full or part-time Employment: Duality Biologics; Financial Interests, Personal, Leadership Role: Duality Biologics; Financial Interests, Personal, Stocks/Shares: Duality Biologics. X. Qiu, R. Shi, L. Liu, P. Miao: Financial Interests, Personal, Full or part-time Employment: Duality Biologics.