A phase I/II, open-label, multicenter study to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of HB0036 in patients with advanced solid tumors.

Abstract

e14504 Background: HB0036 is a bispecific IgG1 antibody targeting both human programmed death ligand 1 (PD-L1) and the T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT). Here we report the initial results from the first-in human study ofHB0036 in patients with advanced malignancies. Methods: This is a first-in-human, phase I/II, multicenter, dose escalation and dose expansion study of HB0036 administered intravenously to adult pts with resistant/ refractory advanced or metastatic solid tumors who had failed standard therapies. Monotherapy of HB0036 will be conducted in 72 enrolled subjects. In the dose escalation phase (phase I), an accelerated titration followed by a 3+3 design was used to dose escalation by assessing the safety and tolerability of HB0036 monotherapy (dose range 0.04 mg/kg to 30 mg/kg), and determine the maximum tolerated dose (MTD). HB0036 was administered Q3w on a 21-day treatment cycle and dose-limiting toxicity (DLT) was observed in first treatment cycle. Tumor assessments per RECIST v1.1 were performed once every 6 weeks (2 cycles). HB0036 PK and PD analyses were performed. Results: At cutoff date of Jan 2, 2024, 19 pts (11 females and 8 males; ECOG 0/1, 3/16) with advanced refractory solid tumors have been enrolled in phase I (0.04 mg/kg [n = 1], 0.12 mg/kg [n = 1], 0.36 mg/kg [n = 1], 1 mg/kg [n = 3], 3 mg/kg [n = 3], 6 mg/kg [n = 3], 10 mg/kg [n = 4], 20 mg/kg [n = 3]). The median age was 59 (range 29-80) years. The pts were heavily pretreated with a median of 2 (range 1-4) prior lines of therapy. No DLT was observed. 13 (68.4%) pts experienced treatment-related adverse events (TRAEs), with 1 pt (5.3%) experienced grade ≥3 TRAEs. No grade 5 TRAE occurred. The incidence or severity of AE was not associated with the dose. The most common TRAEs (≥10%) were blood bilirubin increased, anemia, infusion-related reaction, AST elevated, ALT elevated, bilirubin conjugated increased, fever, hypertriglyceridemia, hypoalbuminemia, hypothyroidism and pyrexia. No SAEs related to HB0036 have been reported. As of DEC 25,2023, in 13 pts who had undergone at least 1 post-baseline tumor assessment, the investigator-assessed best response included 9 SDs and 4 PDs. The DCR was 69% (9/14, 95% CI, 38.6%-90.9%). Durable clinical benefit (SD for > 36 weeks) was seen in 1 subject (3 mg/kg) with lung sarcomatoid carcinoma. HB0036 has presented safe and well-tolerated profile up to doses of 20 mg/kg. To date, 5 responders are still on treatment. The dose escalation is still in progress. Conclusions: HB0036 showed an acceptable safety profile and promising anti-tumor activity in advanced solid tumors, which supports further studies to explore the safety and efficacy of HB0036 as a monotherapy and combination with other anti-tumor agents. Based on these data, phase II monotherapy and combination studies are in preparation. Clinical trial information: NCT05417321 .