PO.CT01.02 · 临床试验
From preclinical models to first-in-human evaluation of STC-1010 immunotherapy in unresectable advanced colorectal cancer
作者与单位
摘要 Abstract
Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer death. It comprises two biological subtypes: microsatellite-stable (MSS, 85-95%) and microsatellite-instable (MSI-H) tumors. While MSI-H tumors respond to immunotherapy, MSS tumors remain “cold” and rely on chemotherapy. STC-1010 is a first-in-class, allogeneic antigen-induced immunotherapy derived from the Stimulated Ghost Cells (SGC) platform. SGC are produced by applying controlled physical or chemical stress to CRC cell lines, followed by haptenation to boost immune recognition; the cells are then inactivated. BreAK CRC 001 is a first-in-human trial evaluating STC-1010 with standard chemotherapy in unresectable advanced CRC. This study aims to translate preclinical findings into the clinical setting by evaluating the immunogenicity and antitumor activity of STC-1010 in combination with chemotherapy.
Methods: Multi-omics analyses were performed to identify STC-1010 antigens relevance to CRC heterogeneity. The anti-tumor activity of a murine surrogate was evaluated in syngeneic CRC models. Mechanistic studies were conducted ex vivo to evaluate STC-1010-primed CD8⁺ T cells killing potency against CRC cell lines. BreAK CRC 001 is a first-in-human, open-label phase I/IIa study of STC-1010 combined with low-dose of cyclophosphamide, GM-CSF (STC-1010 regimen), and associated to standard chemotherapy for unresectable locally advanced or metastatic CRC. Phase I evaluated safety, dose-limiting toxicities, and recommended phase II dose (RP2D); phase IIa will assess safety, clinical activity and immune responses.
Results: STC-1010 provides a broad repertoire of immunogenic antigens capturing CRC heterogeneity. In murine models, mSTC-1010 reduced tumor burden, improved survival, and, when combined with FOLFOX chemotherapy, significantly decreased tumor volumes compared with control. These effects were associated with increased CD8⁺ T cell infiltration. Ex vivo, CD8⁺ T cells primed by STC-1010-treated dendritic cells induced robust apoptosis in multiple CRC cell lines (HCT116, HT29, SW620). As of January 2026, 6 patients with unresectable metastatic CRC received STC-1010 regimen with SOC chemotherapy in the phase I dose-escalation part. Treatment was well tolerated, with predominantly grade 1 infusion-related reactions and no dose-limiting toxicities at the first two dose levels. Despite variable treatment duration, preliminary clinical activity was observed, including partial responses and stable disease per RECIST v1.1.
Conclusion: STC-1010 regimen restores anti-tumor immunity and enhances immune cell activation in CRC models, supporting its continued clinical development. Combined with chemotherapy, it showed a manageable safety profile and early signs of clinical activity, consistent with the antitumor effects observed in preclinical models.
利益披露 Disclosure
D. Tosi,
Brenus Independent Contractor, Institutional funding.
Mabqi Independent Contractor.
Tes Pharma Independent Contractor.
AAA Travel, Meeting attendance.
Pfizer Travel, Meeting attendance.
MSD Travel, Meeting attendance.
Ipsen Travel, Meeting attendance.
Novartis Other, Meeting inscription fee.
A. Italiano,
Bayer ).
Merck ).
MSD ).
BMS ).
AstraZeneca ).
Roche ).
Amgen ).
A. Hollebecque,
Amgen Travel.
Roche Travel.
Incyte Independent Contractor.
Taiho Independent Contractor.
Abbvie Other.
B. You,
Roche/Genentech Independent Contractor.
AstraZeneca Independent Contractor.
Novartis Independent Contractor.
GSK-Tesaro Independent Contractor.
Bayer Independent Contractor.
Amgen Independent Contractor.
Clovis Oncology Independent Contractor.
MSD Independent Contractor.
Merck KGaA Independent Contractor.
Pharma& Independent Contractor.
ECS Progastrin Independent Contractor.
Gilead Independent Contractor.
Myriad Genetics Independent Contractor.
Seagen Independent Contractor.
BMS Independent Contractor.
Menarini Independent Contractor.
Eisai Independent Contractor.
Abbvie Independent Contractor.
See2Cure company Stock.
P. Cassier,
AstraZeneca; Boehringer Ingelheim; Brenus Pharma; Bristol Myers Squibb; GreyWolf therapeutics; MabQuest; Merck Sharp Dohme; Ose Immunotherapeutics; Pierre Fabre; Servier; Scenic Independent Contractor.
Novartis; Pierre Fabre Travel.
Debio Pharm; GSK; Merck Sharp Dohme; Novartis Other, Non-financial support.
Abbvie; Adlai Nortye; Amgen; Arcus; Astellas; Boehringer Ingelheim; Blueprint; C4 Therapeutics; Debio Pharm; Daiichi Sankyo; Dragonfly; Ellipse; Exelixis; Incyte; Iteos; Ipsen; Janssen; Kinnate ).
Lilly/Loxo; Mabquest; Molecular Partners; Novartis; Ose Immunotherapeutics; Pierre Fabre; Regeneron; Relay; Roche/Genentech; Sotio; Taiho; Tango; Toray; Transgene ).
F. Sclafani,
AMAL Therapeutics Independent Contractor.
Amgen Independent Contractor, ), Travel.
Bayer Independent Contractor, ), Travel.
BMS Independent Contractor, ).
Dragonfly Therapeutics Independent Contractor.
GSK Independent Contractor.
Medimix Independent Contractor.
Merck Independent Contractor, ), Travel.
Nordic Pharma Independent Contractor.
Roche Independent Contractor, ), Travel.
Servier Independent Contractor, ), Travel.
AstraZeneca ), Travel.
Astellas ).
Sanofi ).
MSD ).
Pierre-Fabre ).
Sanofi ).
Eli Lilly Travel.
D. Tougeron,
Pierre Fabre ), Travel.
Gilead ).
Roche ), Travel.
MSD ), Travel.
Takeda ).
Servier ), Travel.
Amgen ), Travel.
Astrazeneca Travel.
E. Christenson,
Boston Scientific; Parabilis; Roche; Seres Therapeutics; SirTex; Tatum Biosciences; Urogen Independent Contractor.
Affimed GMBH; Parabilis; Haystack; Incyte; NextCure; Pfizer; Regeneron ).
NextCure Travel.
Brenus Pharma Uncompensated Relationship.
C. Gongora, None.
I. Richert,
Brenus Pharma Employment.
G. Alzeeb,
Brenus Pharma Employment.
P. Marteau, None.
M. Brun,
Brenus Pharma Employment.
L. Feki,
Brenus Pharma Employment.
L. Chalus,
Brenus Pharma Employment.
B. Pinteur,
Brenus Pharma Employment.
P. Bravetti,
Brenus Pharma Employment.
S. Kerbouche,
Brenus Pharma Employment.
C. Tortorelli,
Brenus Pharma Employment.
F. Ghiringhelli,
AstraZeneca ).
Roche ).
Servier Travel.
Amgen Travel.
MSD Travel.