Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55092-2 |
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| author | 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 Edward F. Patz |
| author_facet | 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 Edward F. Patz |
| author_sort | Jeffrey M. Clarke |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d6c5fe0d4de14eb8a7276b6c8c2bf723 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-d6c5fe0d4de14eb8a7276b6c8c2bf7232025-01-05T12:38:18ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-024-55092-2Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trialJeffrey M. Clarke0George R. Simon1Hirva Mamdani2Lin Gu3James E. Herndon4Thomas E. Stinchcombe5Neal Ready6Jeffrey Crawford7Guru Sonpavde8Stephen Balevic9Andrew B. Nixon10Michael Campa11Elizabeth B. Gottlin12Huihua Li13Ruchi Saxena14You Wen He15Scott Antonia16Edward F. Patz17Duke Cancer InstituteH Lee Moffitt Cancer Center—Advent Health Clinical Research UnitKarmanos Cancer Institute, Wayne State UniversityDuke Cancer InstituteDuke Cancer InstituteDuke Cancer InstituteDuke Cancer InstituteDuke Cancer InstituteKarmanos Cancer Institute, Wayne State UniversityDuke University School of MedicineDuke Cancer InstituteDuke University School of MedicineDuke University School of MedicineDuke University School of MedicineDuke University School of MedicineDuke University School of MedicineDuke Cancer InstituteGrid TherapeuticsAbstract 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.https://doi.org/10.1038/s41467-024-55092-2 |
| spellingShingle | 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 Edward F. Patz Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial Nature Communications |
| title | Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial |
| title_full | Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial |
| title_fullStr | Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial |
| title_full_unstemmed | Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial |
| title_short | Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial |
| title_sort | complement factor h targeting antibody gt103 in refractory non small cell lung cancer a phase 1b dose escalation trial |
| url | https://doi.org/10.1038/s41467-024-55092-2 |
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