A Phase I First-Time-in-Human, Open-label Study of Nelistotug Administered to Patients with Advanced Solid Tumors
18 affiliations
- 1Princess Margaret Cancer Centre, Toronto, Canada.
- 2The Angeles Clinic and Research Institute Inc, A Cedars-Sinai Affiliate, Los Angeles, California.
- 3Mary Crowley Cancer Research Center, Sarah Cannon Research Institute at Mary Crowley, Dallas, Texas.
- 4The University of Texas MD Anderson Cancer Center, Houston, Texas.
- 5The Ottawa Hospital Cancer Centre, Ottawa, Canada.
- 6Dana-Farber Cancer Institute, Boston, Massachusetts.
- 7Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
- 8Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
- 9Oncology Clinical Development, GSK, Cambridge, Massachusetts.
- 10Oncology Clinical Development, GSK, Waltham, Massachusetts.
- 11Oncology Clinical Development, GSK, Mississauga, ON, Canada.
- 12Clinical Pharmacology, Modeling and Simulation, GSK, Collegeville, Pennsylvania.
- 13Development Oncology Biostatistics, GSK, Stevenage, United Kingdom.
- 14Oncology Translational Medicine, GSK, Rockville, Maryland.
- 15Biomarkers and Analytical Platforms, GSK, Collegeville, Pennsylvania.
- 16Oncology Clinical Development, GSK, Collegeville, Pennsylvania.
- 17Oncology Clinical Development, GSK, Baar, Switzerland.
- 18National Cancer Center Hospital, Tokyo, Japan.
Abstract
Purpose:: This first-in-human, nonrandomized, multicenter study investigated nelistotug [anti–cluster of differentiation (CD) 96 monoclonal antibody (mAb)] as monotherapy (arm A), in combination with dostarlimab [anti–programmed cell death protein 1 (PD-1) mAb; arm B], and dostarlimab plus belrestotug [anti–T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) mAb; arm F] in patients with recurrent or advanced solid tumors.
Patients and Methods:: Patients received intravenous doses every 3 weeks of nelistotug 2.1 to 1,400 mg, nelistotug 70 to 1,400 mg plus dostarlimab 500 mg, or nelistotug 1,400 mg plus dostarlimab 500 mg plus belrestotug 400 mg in arms A, B, and F, respectively. Primary endpoints were dose-limiting toxicities (DLT) and adverse events (AE). Secondary endpoints included objective response rate, pharmacokinetics, and immunogenicity. Disease control rate and CD96 receptor occupancy were exploratory.
Results:: Thirty-six, 33, and 3 patients were included in arms A, B, and F, respectively. No DLTs were observed in any arm, allowing for dose escalation to nelistotug maximum planned dose in arms A and B, with a recommended phase II dose of 1,400 mg. No treatment-related fatal AEs were observed. In arm B, 1 (3%) patient achieved a complete response and 1 (3%) achieved a partial response; no responses were observed in arms A and F. Nelistotug serum concentrations across doses were calculated to be sufficient to saturate the target in the tumor since >95% CD96 receptor occupancy was observed in peripheral blood immune cells.
Conclusions:: Nelistotug as monotherapy and in combination with dostarlimab and belrestotug had an acceptable safety and tolerability profile; however, efficacy was limited in this heavily pretreated patient population with advanced solid tumors.
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BibTeX
@article{siu2026phase,
title = {{A Phase I First-Time-in-Human, Open-label Study of Nelistotug Administered to Patients with Advanced Solid Tumors}},
author = {Lillian L. Siu and Omid Hamid and Reva Schneider and Jordi Rodon Ahnert and Scott A. Laurie and Frank Stephen Hodi and Dong-Wan Kim and Myung-Ju Ahn and Gary Carlson and Hussein Assi and Hamza Khan and Patrick Hanafin and Emily Moore and Madhu Ramaswamy and Reza Mozaffari and Stefan Zajic and Arindam Dhar and Ivan Diaz Padilla and Noboru Yamamoto},
journal = {Clinical Cancer Research},
year = {2026},
month = aug,
doi = {10.1158/1078-0432.ccr-25-4374},
url = {https://doi.org/10.1158/1078-0432.ccr-25-4374},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Phase I First-Time-in-Human, Open-label Study of Nelistotug Administered to Patients with Advanced Solid Tumors
AU - Lillian L. Siu
AU - Omid Hamid
AU - Reva Schneider
AU - Jordi Rodon Ahnert
AU - Scott A. Laurie
AU - Frank Stephen Hodi
AU - Dong-Wan Kim
AU - Myung-Ju Ahn
AU - Gary Carlson
AU - Hussein Assi
AU - Hamza Khan
AU - Patrick Hanafin
AU - Emily Moore
AU - Madhu Ramaswamy
AU - Reza Mozaffari
AU - Stefan Zajic
AU - Arindam Dhar
AU - Ivan Diaz Padilla
AU - Noboru Yamamoto
PY - 2026
DA - 2026/08/27
JO - Clinical Cancer Research
DO - 10.1158/1078-0432.ccr-25-4374
UR - https://doi.org/10.1158/1078-0432.ccr-25-4374
AB - Purpose:: This first-in-human, nonrandomized, multicenter study investigated nelistotug [anti–cluster of differentiation (CD) 96 monoclonal antibody (mAb)] as monotherapy (arm A), in combination with dostarlimab [anti–programmed cell death protein 1 (PD-1) mAb; arm B], and dostarlimab plus belrestotug [anti–T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) mAb; arm F] in patients with recurrent or advanced solid tumors. Patients and Methods:: Patients received intravenous doses every 3 weeks of nelistotug 2.1 to 1,400 mg, nelistotug 70 to 1,400 mg plus dostarlimab 500 mg, or nelistotug 1,400 mg plus dostarlimab 500 mg plus belrestotug 400 mg in arms A, B, and F, respectively. Primary endpoints were dose-limiting toxicities (DLT) and adverse events (AE). Secondary endpoints included objective response rate, pharmacokinetics, and immunogenicity. Disease control rate and CD96 receptor occupancy were exploratory. Results:: Thirty-six, 33, and 3 patients were included in arms A, B, and F, respectively. No DLTs were observed in any arm, allowing for dose escalation to nelistotug maximum planned dose in arms A and B, with a recommended phase II dose of 1,400 mg. No treatment-related fatal AEs were observed. In arm B, 1 (3%) patient achieved a complete response and 1 (3%) achieved a partial response; no responses were observed in arms A and F. Nelistotug serum concentrations across doses were calculated to be sufficient to saturate the target in the tumor since >95% CD96 receptor occupancy was observed in peripheral blood immune cells. Conclusions:: Nelistotug as monotherapy and in combination with dostarlimab and belrestotug had an acceptable safety and tolerability profile; however, efficacy was limited in this heavily pretreated patient population with advanced solid tumors.
SN - 1078-0432
SN - 1557-3265
ER -