29P - A phase I, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, antitumor activity of QL1604, a humanized anti-PD-1 mAb, in patients with advanced solid tumors

Background

PD-1 inhibitor has demonstrated promising efficacy in various solid tumors. Here we report the safety, efficacy, ADA, RO and PK/PD results from a phase I study of QL1604, a humanized anti-PD-1 mAb in pts with advanced solid tumors.

Methods

Pts with histologically or cytologically confirmed advanced solid tumors, had ≥1 target lesion (RECIST 1.1), and failed standard therapy were enrolled. The study included 2 parts: dose escalation and dose expansion. In the dose-escalation part, a titration design combined with 3+3 method was used. Pts received QL1604 at 0.3mg/kg, 1mg/kg, 3mg/kg, and 10mg/kg dose levels (DLs) Q2W in each 4-week treatment cycle until disease progression or other discontinuation events. The observation period for DLT was 4 weeks after the first dose at each DL. In the dose-expansion part, pts received QL1604 at 3 mg/kg Q2W, 10 mg/kg Q2W, 3 mg/kg Q3W, and 200 mg Q3W DLs. The primary endpoints included MTD, safety, the recommended dose for future clinical studies.

Results

As of 16 Dec 2022, 35 pts were enrolled in 2 sites in China. 18 (51.4%) pts had NSCLC. 32 (91.4%) pts had an ECOG PS of 1. 18 (51.4%) pts previously received ≥3 lines of therapy. 29 (82.9%) pts experienced TRAEs. The most common TRAEs (≥20%) were asthenia (37.1%) and anemia (22.9%). 6 (17.1%) pts experienced Gr ≥3 TRAEs. DLTs were observed in 1 pt (thymic cancer) at 3 mg/kg Q2W DL: Gr 3 immune-mediated myositis and myasthenia gravis. The MTD was not reached. 7 pts had PR (1 to 10 mg/kg Q2W or Q3W and 200 mg/kg Q3W; 5 pts with NSCLC and 2 pts with nasopharyngeal carcinoma). The ORR was 20% (7/35) and DCR was 34.3% (12/35). The AUC and C_max increased in an approximately dose-proportional manner in the dose range 0.3 mg/kg to 10 mg/kg. 3 pts tested ADA positive at baseline and 16 pts had at least one positive result after dosing. RO was >80% on day 15 and day 22 at 3 mg/kg Q2W, 3 mg/kg Q3W, and 200 mg Q3W DLs.

Conclusions

QL 1604 showed good safety profile and efficacy signal in the dose range of 0.3 to 10 mg/kg (Q2W or Q3W) and at a fixed dose of 200 mg Q3W for pts with advanced solid tumors. 3 mg/kg Q3W and 200 mg Q3W were chosen as the recommended doses for future clinical studies.

Clinical trial identification

NCT05649761.

Editorial acknowledgement

Legal entity responsible for the study

Qilu Pharmaceutical Co., Ltd.

Funding

Qilu Pharmaceutical Co., Ltd.

Disclosure

W. Feng, L. Li, B. Zhang, B. Zhang: Other, Personal, Full or part-time Employment: Qilu Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.