Safety results of Q-1802, a Claudin18.2/PD-L1 bsABs, in patients with relapsed or refractory solid tumors in a phase 1 study.

2568 Background: Q-1802 is a humanized bispecific antibody that targets both the tumor -specific antigen CLDN18.2 and the immune checkpoint PD-L1. Methods: This is a first-in-human, phase 1a/1b, multicenter, dose escalation and dose expansion study of Q-1802 administered intravenously to adult pts with resistant/refractory advanced or metastatic solid tumors who had failed standard therapies. Monotherapy of Q-1802 was conducted in 20-30 enrolled subjects. In the dose escalation phase (phase 1a), an accelerated titration followed by a 3+3 design was used to assess the safety and tolerability of Q-1802 monotherapy (dose range 0.1 mg/kg to 20 mg/kg); and determine the maximum tolerated dose (MTD). Q-1802 was administered Q3w on a 21-day treatment cycle and dose limiting toxicity (DLT) observation period. Tumor assessments per RECIST v1.1 were performed once every 6 weeks (2 cycles). Q-1802 PK and PD analyses were performed. Results: As of Jan 20, 2022, a total of 9 patients (median age 57y; most patients received ≥3 prior regimens) were enrolled in phase 1a with DLT evaluation of the 20 mg/kg cohort currently in progress. The most common tumor types were GI cancers. There were no DLTs up to 10 mg/kg of Q-1802, inclusive. Phase 1a with DLT evaluation of the 20 mg/kg cohort currently in progress. The most common treatment related adverse events (TRAEs) were Gastrointestinal AE (66.7%, 6/9), including nausea 6/9 (66.7%), vomiting 5/9 (55.6%), abdominal pain 2/9 (22.2%) and diarrhea 2/9 (22.2%). The second common TRAEs were IRR (infusion related reaction) (33.3%, 3/9), including Fatigue 3/9 (33.3%), Fever 2/9 (22.2%), Chill 2/9 (22.2%), face pain 1/9 (11.1%). There was G1/2 except for one patient experienced a G3 skin rash, and one patient reported with a G3 Gastrointestinal AE. Two SAEs (G2 fever and G3 Gastrointestinal AE) were reported, both were considered as possibly related to study drug, but recovered shortly. No death reported due to study related treatment. Safety evaluation of the 20 mg/kg dose level is in progress. One Gastric cancer patient (moderate CLDN18.2 expression at baseline) with prior heavily treatment observed clinical benefit and response with Non-CR/Non-PD at first tumor assessment at dose of 10mg/kg and continues the therapy. Q-1802 drug exposure increased with increasing dose. The elimination of Q-1802 appears to follow first-order elimination kinetics. Conclusions: Q-1802 bsABs has presented safe and well-tolerated profile up to doses of 10 mg/kg. The dose escalation is still in progress. Clinical trial information: NCT04856150.