Phase 1 study of LB1410, a bivalent TIM-3/PD-1 bispecific antibody, in patients with advanced solid tumors or lymphoma.

Abstract

2586 Background: LB1410 is a recombinant humanized anti-PD-1/TIM-3 bispecific antibody (BsAb) developed by L&L Biopharma Co., Ltd. for patients (pts) resistant to or refractory to PD-1/PD-L1 treatments, showing superior T/DC cell activity and in vivo anti-tumor efficacy compared to a combination of TIM-3 and PD-1 antibodies in preclinical studies. Here, we report the dose escalation and dose expansion results of LB1410 as monotherapy in patients with advanced solid tumors (Keyplus-001). Methods: Eligible patients were ≥18 years old with ECOG PS 0-1 and advanced solid tumors. Dose cohorts ranged from 0.001 mg/kg to 20 mg/kg IV Q2W: 0.001 mg/kg-1 mg/kg in an accelerated titration design, and 3 mg/kg - 20 mg/kg using a traditional 3+3 design. Selected dose levels were expanded in patients with advanced clear cell renal cell carcinoma (ccRCC) and cervical cancer (CC). The primary objective was safety, including dose-limiting toxicities (DLTs). Secondary/exploratory objectives included efficacy, pharmacokinetics (PK), and immunogenicity. Results: As of January 15, 2025, a total of 79 patients received LB1410 at doses ranging from 0.001 mg/kg to 20 mg/kg as of January 15, 2025. The median age was 59 years, and 70% of patients were male. All enrolled patients had multiple organ metastases or multiple metastases in a single organ and were heavily pretreated with anti-tumor therapies. Of the patients, 76.9% (60/79) had solid tumors that had failed standard therapies and were resistant or refractory to anti-PD-1/PD-L1 treatments. Treatment-related adverse events (TRAEs) occurred in 63.3% of patients. The most common TRAEs (≥10%) included anemia (24.1%), proteinuria (12.7%), increased alanine aminotransferase (11.4%), increased aspartate aminotransferase (11.4%), hyponatremia (10.1%), increased blood lactate dehydrogenase (10.1%), and weight loss (10.2%). Grade 3 TRAEs occurred in 7 patients, including 3 with hypokalemia, 2 with hypertension, 1 with hyponatremia, 1 with proteinuria, and 1 with pulmonary embolism. No dose-limiting toxicities (DLTs) were observed. On- treatment scan was available for 66 patients. The observed overall response rate (ORR) per RECIST 1.1 was 3/66 (4.5%), with 3 confirmed partial responses (PRs) in patients with ccRCC and CC. The disease control rate (DCR) was 45.5% (30/66). In patients with ccRCC, the ORR was 16.7% (1/6), and the DCR was 66.7% (4/6). In patients with CC, the ORR and DCR were both 66.7% (2/3). Of the 27 patients with stable disease, 3 had stable disease for nearly 12 months, and 2 of them are still receiving ongoing treatment in the study. Conclusions: LB1410 has a manageable safety profile and demonstrates potential efficacy at tolerable doses in heavily pretreated patients, particularly those with immune-oncology (IO)-refractory or resistant ccRCC and CC. Clinical trial information: NCT05357651 .