LM-101, an anti-SIRPα antibody, in patients with relapsed/refractory lymphoma and advanced head and neck cancer: an open-label, multicenter, phase 1 trial.

Abstract

To evaluate the safety and preliminary antitumor activity of LM-101, an anti-SIRPα antibody that blocks the CD47-SIRPα interaction, as monotherapy and in combination with rituximab or toripalimab in relapsed/refractory lymphoma and advanced head and neck cancer. Adult patients with relapsed/refractory lymphoma or advanced head and neck cancer were eligible. In the dose-escalation phase, patients received LM-101 with accelerated titration at 3 mg/kg every three weeks, followed by a 3+3 escalation at 10, 20, 30, and 40 mg/kg. In the combination therapy safety lead-in phase, LM-101 was given at the recommended phase 2 dose (RP2D) with rituximab in lymphoma and with toripalimab in head and neck cancer. The primary objective was safety. Secondary objectives included antitumor activity. gov: NCT05615974. Between January 17, 2023, and October 06, 2025, 36 patients received LM-101 monotherapy (n=17), LM-101 plus rituximab (n=10), or LM-101 plus toripalimab (n=9). No dose-limiting toxicities were observed. The RP2D was 40 mg/kg every three weeks. Grade ≥3 hematologic treatment-related adverse events (TRAEs) included lymphopenia (5.9% with monotherapy; 40% with LM-101 plus rituximab), neutropenia (5.9%; 20%, respectively), and leukopenia (5.9%; 20%, respectively). Non-hematologic TRAEs were infrequent and predominantly grade 1-2. Objective response rates were 17.6% (3/17) with monotherapy and 50.0% (4/8) with LM-101 plus rituximab. Disease control rates were 75.0% (6/8) for LM-101 plus rituximab and 42.9% (3/7) for LM-101 plus toripalimab (with no objective responses observed). LM-101 was well tolerated. The preliminary efficacy signal supports further evaluation of LM-101 plus rituximab in relapsed/refractory lymphoma.