Abstract
Trial START-001: A phase 1/2 study of STAR0602, a first-in-class, selective T cell receptor (TCR)-targeting, bifunctional antibody-fusion molecule, as monotherapy in patients with antigen-rich tumors post checkpoint inhibitor (CPI) treatment.
Author
Ryan J. Sullivan
Massachusetts General Hospital, Boston, MA
info_outline
Ryan J. Sullivan, Ke Liu, Jason M. Redman, Nicholas Tschernia, Andrew Bayliffe, Alyssa Marino, Karunya Srinivasan, Madan Katragadda, Jacques Moisan, Rajesh Chopra, Aurelien Marabelle, Howard L. Kaufman, Lillian L. Siu, Zhen Su, James L. Gulley
Full text
Authors
Ryan J. Sullivan
Massachusetts General Hospital, Boston, MA
info_outline
Ryan J. Sullivan, Ke Liu, Jason M. Redman, Nicholas Tschernia, Andrew Bayliffe, Alyssa Marino, Karunya Srinivasan, Madan Katragadda, Jacques Moisan, Rajesh Chopra, Aurelien Marabelle, Howard L. Kaufman, Lillian L. Siu, Zhen Su, James L. Gulley
Organizations
Massachusetts General Hospital, Boston, MA, Marengo Therapeutics, Inc, Cambridge, MA, Center for Immuno-Oncology, CCR, NCI, NIH, Bethesda, MD, Center for Immuno-Oncology, CCR, NCI, NIH, Bethesda, MD, Gustave Roussy Cancer Campus, Villejuif, France, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada, Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Marengo Therapeutics, INC
Background:
Many patients do not respond to CPI-based therapies and most responders eventually develop resistance. Thus, the development of more effective therapies for CPI treatment resistance is a significant unmet medical need. STAR0602, a first-in-class, TCR β chain-targeting bifunctional antibody fused to a costimulatory molecule, binds the germline Vβ6/Vβ10 TCRs of human alpha/beta (aβ) T cells, and promotes the selective activation and expansion of CD8
+
and CD4
+
Vβ6/Vβ10 effector memory T cells by simultaneously engaging direct TCR activation with IL-2 receptor binding and activation in
cis
. Preclinical studies with STAR0602 and its murine surrogate showed potent single-agent anti-tumor activity in multiple CPI-refractory human organoid and murine syngeneic tumor models, and acceptable tolerability and limited cytokine release in monkeys and mice. Durable anti-tumor responses, with long-term protection from tumor re-challenge, was associated with
de novo
expansion and tumor infiltration of targeted Vβ T cell subsets with a novel effector memory gene signature and striking increase in TCR repertoire diversity. These data provide strong scientific rationale to investigate the safety and efficacy of STAR0602 in patients with CPI-resistant cancers.
Methods:
Using a 3+3 trial design, Phase 1 of START-001 is a dose escalation through eight provisional dose levels of STAR0602, administered via an intravenous infusion once every two weeks, to determine a recommended Phase 2 dose (RP2D), based on safety and tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity. Subjects must have one of the following, histologically confirmed solid tumors that are unresectable, locally advanced or metastatic and for which standard curative therapies do not exist or are no longer effective: 1) high mutational burden solid tumors (TMB-H); 2) MSI-H/mismatch repair-deficient (dMMR) cancers; 3) Virally associated tumors including Merkel cell carcinoma, cervical, oropharyngeal, anal, penile, vaginal, and vulval cancers. After an RP2D is selected, Phase 2 (dose expansion at this RP2D) will begin to further investigate the safety and preliminary anti-tumor activity of STAR0602 in 10 provisional cohorts of patients who have the following solid tumors: TMB-H, CPI experienced; TMB-H, no prior CPI experience; MSI-H/dMMR; virally associated tumors; K-RAS wild-type and MSI-L/MMR proficient colorectal cancer (CRC); K-Ras mutant CRC; metastatic triple-negative breast cancer; relapsed and refractory epithelial ovarian cancer; metastatic castration-resistant prostate cancer; primary stage IV or recurrent non-small cell lung cancer. Phase 1 enrollment has begun since January 2023. Clinical trial information: NCT05592626.
Clinical status
Clinical
1 clinical trial
7 organizations
1 drug
3 targets
Clinical trial
A Phase 1/2, First-in-Human, Open-Label, Dose Escalation and Expansion Study of STAR0602, a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule, in Subjects With Unresectable, Locally Advanced, or Metastatic Solid Tumors That Are Antigen-rich (START-001)Status: Recruiting, Estimated PCD: 2026-10-01
Organization
Marengo TherapeuticsOrganization
Center for Immuno-Oncology, CCR, NCI, NIHOrganization
Center for Immuno-Oncology, CCR, NCI, NIHOrganization
Gustave Roussy Cancer CampusDrug
STAR0602Target
Vβ10 TCRTarget
Vβ6 TCRTarget
IL-2 receptor