A phase Ia trial to evaluate the safety and efficacy of HB0030, an anti-TIGIT antibody, in patients with advanced solid tumors: Preliminary results.

Abstract

e14673 Background: HB0030 is an IgG1 type humanized monoclonalanti-TIGIT antibody. Its heavy chain Fc fragment is wild-type that preserves function for inducting CDC and ADCC effects. Nonclinical data showed that HB0030 has a good affinity for TIGIT and anti-tumor activity. Methods: This is an ongoing single-center, open-label, dose escalation Phase Ia study to mainly evaluate HB0030 safety, antitumor activity and immunogenicity in patients (pts) with advanced solid tumor. HB0030 is administered by IV infusion every 21 days. An accelerated titration method combined the standard 3+3 design was utilized for dose escalation, which of contained 8 dose groups (0.1, 0.3, 1.0, 3.0, 10, 20, 30, 40mg/kg). The tumor assessment evaluated by investigator according to RECIST v1.1. Results: As of Jan 9, 2023, 20 pts (4Male/16Female) with advanced malignant solid tumor have been enrolled and dosed at 0.1mg/kg (n = 1), 0.3mg/kg (n = 3), 1mg/kg (n = 3), 3mg/kg (n = 4), 10mg/kg (n = 3) and 20mg/kg (n = 6). The median age was 56.9 years. All pts had stage IV disease and failed from the anti-tumor standard therapy with a median of 3 lines. The main tumor types included lung(n = 6), breast(n = 3), colorectal(n = 3) and cervical (n = 2) cancer. Total 16 pts have completed at least once tumor assessment. The ORR and DCR were 6.3% (1/16) and 62.5% (10/16), respectively. The best response was a PR with 47% tumor regression pt who was diagnosed non-small cell lung cancer (NSCLC) accompanied with TP53 gene mutation. The pt relapsed with multiple metastasis after radical operation and adjuvant chemotherapy, and failed to systemic chemotherapy combined targeting anti-vascular therapy. He achieved PR with 3 cycles of 20mg/kg HB0030 treatment, and PR status continued at present. A NSCLC pt maintained 24 weeks SD after 3mg/kg HB0030 administration. The most common treatment related adverse events (TRAEs) were lymphopenia (9/20, 45%) and shortened activated partial thromboplastin time (APTT) (6/20,30%). Grade 3 TRAEs occurred in 15% of pts (3/20) which included thrombocytopenia, anemia, syncope and hypertension. There were no Grade 4-5 AEs, serious adverse events (SAEs), dose-limiting toxicity (DLT) and death. The anti-drug antibodies (ADAs) were detected in 2 pts in 20 mg/kg dose group, and not caused by HB0030 therapy because it had existed in baseline. Conclusions: HB0030 showed very well safety in the stage of dose escalation from 0.1 to 20 mg/kg, and potential promising anti-tumor activity above 3mg/kg dose in advanced solid tumors pts, especially in NSCLC. Currently, 30mg/kg and 40mg/kg dose escalation are ongoing. Clinical trial information: NCT05706207 .