Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial

Jeffrey M. Clarke (), George R. Simon, Hirva Mamdani, Lin Gu, James E. Herndon, Thomas E. Stinchcombe, Neal Ready, Jeffrey Crawford, Guru Sonpavde, Stephen Balevic, Andrew B. Nixon, Michael Campa, Elizabeth B. Gottlin, Huihua Li, Ruchi Saxena, You Wen He, Scott Antonia and Edward F. Patz ()
Additional contact information
Jeffrey M. Clarke: Duke Cancer Institute
George R. Simon: H Lee Moffitt Cancer Center—Advent Health Clinical Research Unit
Hirva Mamdani: Wayne State University
Lin Gu: Duke Cancer Institute
James E. Herndon: Duke Cancer Institute
Thomas E. Stinchcombe: Duke Cancer Institute
Neal Ready: Duke Cancer Institute
Jeffrey Crawford: Duke Cancer Institute
Guru Sonpavde: Wayne State University
Stephen Balevic: Duke University School of Medicine
Andrew B. Nixon: Duke Cancer Institute
Michael Campa: Duke University School of Medicine
Elizabeth B. Gottlin: Duke University School of Medicine
Huihua Li: Duke University School of Medicine
Ruchi Saxena: Duke University School of Medicine
You Wen He: Duke University School of Medicine
Scott Antonia: Duke Cancer Institute
Edward F. Patz: Grid Therapeutics

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract GT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a “3 + 3” schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103. Secondary objectives included describing objective response rate, progression-free survival and overall survival. Dose escalation cohorts included GT103 given intravenously at 0.3, 1, 3, 10, and 15 mg/kg every 3 weeks, and 10 mg/kg every 2 weeks. Thirty one patients were enrolled across 3 institutions. Two dose-limiting adverse events were reported: grade 3 acute kidney injury (0.3 mg/kg) and grade 2 colitis (1 mg/kg). No dose-limiting toxicities were noted at the highest dose levels and the MTD was not reached. No objective responses were seen. Stable disease occurred in 9 patients (29%) and the median overall survival was 25.7 weeks (95% confidence interval [CI], 19.1–30.6). Pharmacokinetic analysis confirmed an estimated half life of 6.5 days. The recommended phase 2 dose of GT103 was 10 mg/kg every 3 weeks, however further dose optimization is needed given the absence of an MTD. The study achieved its primary objective of demonstrating safety and tolerability of GT103 in refractory NSCLC.

Date: 2025
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DOI: 10.1038/s41467-024-55092-2

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