A phase I clinical study to evaluate the safety, tolerability, and pharmacokinetic characteristics of HLX43 (anti-PD-L1 ADC) in patients with advanced/metastatic solid tumors.

3025 Background: Antigens highly expressed in tumors such as HER2 and TROP2 have been widely investigated as antibody-drug conjugate (ADC) targets, leading to their approval for various cancers due to their promising efficacies. However, limited targets for approved ADCs and resistance to the cytotoxic agents render the imperative need for new ADCs. This study aimed to evaluate the safety, tolerability, and preliminary efficacy of HLX43, a novel anti-PD-L1 ADC in patients with advanced/metastatic solid tumors. Methods: This phase 1 study consisted of 2 parts. Parts 1 and 2 were dose escalation and dose expansion phases, respectively, to explore different doses of HLX43. In Part 1, patients with histologically or cytologically confirmed advanced/metastatic malignant solid tumors refractory to or not amenable to standard therapies received intravenous HLX43 at 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, or 4 mg/kg, Q3W. In Part 2, patients with advanced/metastatic non-small cell lung cancer (NSCLC) refractory to standard treatment received HLX43 at 2 mg/kg, 2.5 mg/kg, or 3 mg/kg, Q3W. The primary endpoints for Part 1 were the proportion of subjects experiencing dose-limiting toxicity (DLT) in each dose group within three weeks after the first drug administration and the maximum tolerable dose (MTD) while that for Part 2 were the recommended Phase 2 dose and IRRC-assessed objective response rate (ORR). Results: As of 27 June 2023, 18 patients with non-small cell lung cancer (n = 12, 66.7%), head and neck squamous carcinoma, cervical squamous carcinoma, thymic squamous cell carcinoma, nasopharyngeal cancer, uterine carcinosarcoma, or small cell lung cancer (n = 1, 5.6% for each) were enrolled in Part 1 and received HLX43 at 0.5 mg/kg (n = 3), 1 mg/kg (n = 3), 2 mg/kg (n = 3), 3 mg/kg (n = 3), or 4 mg/kg (n = 6). All the patients experienced treatment-emergent adverse events (TEAEs) that were mostly grades 1-2. One patient in the 4 mg/kg dose group experienced DLTs of febrile neutropenia and decreased white blood cell count. Investigator-assessed ORR was 31.3% (95% CI 11.0-58.7). In Part 2, only data from 21 patients enrolled to receive HLX43 at 2 mg/kg is available and presented here. Among these patients, 15 (71.4%) had squamous NSCLC and 6 (28.6%) had nonsquamous NSCLC. Investigator-assessed ORR and disease control rate were 38.1% (95% CI 18.1-61.6) and 81.0% (95% CI 58.1-94.6); no complete response was achieved, and 8 patients (6 sqNSCLC and 2 nsqNSCLC) had partial response. All the patients experienced TEAEs, most of which were grades 1-2; grade ≥3 TEAEs occurred in 7 (33.3%) patients. Conclusions: HLX43 was well tolerated with no new safety signals across different dose and exhibited encouraging preliminary efficacy in patients with advanced solid tumors, including those with NSCLC, who had failed standard therapies, which warrants further investigation. Clinical trial information: NCT06115642 .