A phase I/II open label, multicenter study to assess the safety, tolerability, pharmacokinetics, and efficacy of HB0028 in patients with advanced solid tumors.

2528 Background: HB0028 is a bifunctional fusion protein consisting of an anti-PD-L1 IgG1 single domain antibody and TGF-β RII receptor extracellular domain (TGFβRII-ECD). This is the first dose escalation and expansion phase I/II study to evaluate the safety and preliminary anti-tumor activity of HB0028 in advanced solid tumors. Methods: In the phase I portion of the study, the patients (pts) with advanced solid tumor were enrolled, and an accelerated titration followed by a standard 3+3 design was applied to dose escalation. The objectives were toxicity evaluation, maximum tolerable dose (MTD), and recommended phase 2 dose (RP2D). Eligible pts with advanced solid cancers of any histologic subtype, and ECOG performance status ≤ 1 were treated with HB0028 (0.3mg, 1mg, 3mg, 10mg, 20mg, Q3W), until unacceptable toxicity or disease progression. Radiologic tumor assessments (by RECIST v1.1) were performed every 6 weeks while on treatment. Results: 16 pts 12 females and 4 males; ECOG 0/1, 9/7; median age 52 years (range 36 – 60) were enrolled in phase I (0.3 mg/kg n = 1, 1 mg/kg n = 3, 3 mg/kg n = 3, 10 mg/kg n = 3, 20 mg/kg n = 6). Median number of prior lines of systemic therapy was 2 (range 1-4). 8(50%) pts received and progressed upon prior anti-PD-1/L1 therapy. All pts had measurable metastatic disease. No DLT and Death occurred. MTD was not reached. As of DEC 25,2023, among 16 patients' safety data are evaluable for toxicity. Any grade treatment‐related adverse events (TRAEs) occurred in 15 subjects (93.8%), with 2 subjects (12.5%) reported with ≥ Grade 3 (G3 Anemia and G3 γ-glutamyltransferase). The most common TRAEs (all grades) were AST increased (n = 4, 25%), anemia (n = 7, 43.8%) and infusion-related response (n = 5, 31.3%). Two SAEs (G2 AST increased and G3 Neoplastic fevers) were reported, only AST increased was considered as possibly related to study drug, but recovered shortly. The efficacy data cutoff date of DEC 25,2023, 16 patients are evaluable for radiologic response. 1 subject with cervical cancer in HB0028 20 mg/kg group had a partial response (PR), 3 subjects (liver cancer, lung cancer, left submandibular gland cancer) had stable disease (SD) and 12 subjects had progressive disease (PD). The ORR per RECIST 1.1 by investigator was 6.25% (1/16; 95% CI, 0%-30.2%), and the DCR was 25% (4/16; 95% CI, 7.3%-52.4%). Durable clinical benefit (SD for > 32 weeks) was seen in 1 subject with malignant tumor in the left submandibular gland. To date, 2 responders are still on treatment. Conclusions: HB0028 was generally well tolerated, and therapy provided modest antitumor activity in patients with heavily pretreated advanced solid tumors. Based on these data, a phase II prospective clinical trial is being planned in specific cancer. Clinical trial information: NCT06223308 .