Marengo Presents Monotherapy Activity of Invikafusp Alfa, a First-in-Class Selective Dual T Cell Agonist in PD-1 Resistant GI Tumors, as a Late-Breaking Oral Presentation at ESMO Gastrointestinal Cancers Congress 2025

• Promising monotherapy activity observed in all three major metastatic colorectal cancer subtypes harboring high tumor mutational burden (MSS RASwt, MSS RASmut and PD-1 resistant MSI-H) supported by recent FDA fast track designation
  
  
• New clinical response observed in PD-1 resistant gastroesophageal junction (GEJ) tumor
  
  
• Invikafusp alfa demonstrates overall Disease Control Rate of 63%, Tumor Regression Rate of 53% and Objective Response Rate of 23% in heavily pretreated PD-1 resistant TMB-H GI cancer patients

CAMBRIDGE, Mass., July 2, 2025 /PRNewswire/ -- Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision immunotherapy, today presented new clinical data from the ongoing STARt-001 Phase 1/2 trial of Invikafusp alfa during an oral session at the European Society of Medical Oncology (ESMO) Gastrointestinal Cancers Congress 2025.

Presentation Details

• Title: Phase 1/2 clinical investigation of Invikafusp alfa, a first-in-class TCR-beta chain-targeted bispecific antibody, as monotherapy in patients with anti-PD(L)1-resistant, antigen-rich gastrointestinal (GI) cancers
• Abstract Number: 479MO (Late-breaking)
• Session Title: Mini Oral session - Innovation in GI cancers
• Session Date and Time: Thursday, July 2, 2025, 4:15 PM – 5:35 PM CET (UTC+01:00)
• Presenter: Elena Elez, M.D. Ph.D., Vall d'Hebron Institute of Oncology

Invikafusp alfa is Marengo's first-in-class dual T cell agonist, designed with a bi-specific antibody format to selectively engage and activate the Vβ6 and Vβ10 subsets of T cells in vivo, promoting durable anti-tumor immunity. The updated clinical data continue to reinforce invikafusp alfa's potential as a backbone immunotherapy for PD-1 resistant gastrointestinal (GI) cancers, with monotherapy clinical responses observed in both colorectal cancer (CRC) and gastric-esophageal junction (GEJ) cancer, including tumor types where checkpoint inhibitors have very limited monotherapy activity.

"We are thrilled to see high quality single agent clinical activity in multiple PD-1 resistant tumor types including MSS CRC, PD-L1 negative NSCLC and now, additional GI cancers including GEJ cancer," said Zhen Su, M.D., M.B.A., Chief Executive Officer of Marengo Therapeutics. "Invikafusp's ability to drive meaningful responses in both PD-1-resistant/insensitive tumors, and across diverse tissue types, underscores the potential of our precision T cell activation platform to deliver real impact as a new class of IO backbone in immunotherapy-refractory tumors. These results further validate our commitment to advancing invikafusp as next gen IO especially in GI cancers."

"The activity we are observing with invikafusp in both CRC and GEJ tumors is highly compelling and highlights the clinical potential of a novel T cell agonist approach," said Aparna Parikh, M.D., GI Oncologist and Director of Colorectal Medical Oncology and the Center for Young Adult Colorectal Cancer at Massachusetts General Hospital Cancer Center and Harvard Medical School. "Having a new class of cancer immunotherapy with such a differentiated mechanism in GI tumors, especially in those not responsive to checkpoint inhibitors, is truly exciting for the GI cancer research field and cancer patients."

Updated Findings from the ESMO GI 2025 Clinical Plenary Presentation:

• In 17 heavily pretreated PD-1 resistant TMB-H GI cancer patients, invikafusp alfa monotherapy demonstrated:
  • Disease control rate (DCR): 63%
  • Tumor Regression Rate of 53%
  • Overall response rate (ORR): 23%
  • Responses included:
    • Three CRC responders across major molecular subtypes (MSS RASwt, MSS RASmut, PD-1 resistant MSI-H)
    • One objective response in PD-1 resistant MSI-H GEJ
  • In PD-1 resistant TMB-H metastatic CRC specifically, ORR was 25% (3/12 patients)

Safety Profile:

• No new safety signals observed in Phase 2a
• Safety profile consistent with invikafusp alfa's selective T cell activation mechanism
• Adverse events were generally transient and manageable with supportive care

Invikafusp alfa (STAR0602) is a first-in-class, dual T cell agonist designed to selectively activate Vβ6 and Vβ10 T cell subsets in vivo, promoting durable anti-tumor immunity. Marengo is currently enrolling patients in the Phase 2a expansion cohorts of STARt-001 trial across multiple tumor types, including TMB-H metastatic CRC, and MSI-H or TMB-H solid tumors.

About Marengo Therapeutics
Marengo Therapeutics, Inc., a clinical-stage biotech company, develops novel TCR-targeting antibodies that selectively modulate common and disease-specific T cell subsets of the germline TCR repertoire to provide lifelong protection against cancer and autoimmune diseases. With a passionate team of dedicated scientists experienced in immunology and oncology, and three proprietary platforms: Selective T Cell Activation Repertoire (STAR), Trispecific T Cell Engager (Tri-STAR) and T cell Depletor (MSTAR), Marengo is working to selectively target the right T cells in the right patients to create a world in which everyone's immune system can defeat cancer and autoimmune diseases. To learn more, visit marengotx.com.

About the STAR™ Platform
Marengo's STAR™ Platform is a multi-specific antibody-fusion platform derived from Marengo's proprietary library of antibodies targeting germline-encoded variable Vβ regions of the TCR fused to different T cell co-stimulatory moieties. Combining a novel non-clonal mode of TCR activation with a T cell co-stimulator in the same molecule promotes a distinct mechanism of action that promotes durable anti-tumor Vβ T cell responses.

About Invikafusp alfa (STAR0602)
Invikafusp alfa (STAR0602) is the lead candidate from Marengo's STAR™ platform. It is designed to selectively activate a common Vβ T cell subset found in all cancers by combining a non-clonal mode of TCR activation with a T cell co-stimulatory signal in a single molecule. This innovative approach promotes the expansion of clonally diverse, effector memory Vβ T cells, enhancing anti-tumor immunity and enabling durable tumor clearance. Extensive preclinical studies demonstrate STAR0602's potent anti-tumor activity in both mouse and human ex vivo models via a novel mechanism of action. 

About the STARt-001 Clinical Study
STARt-001 is a Phase 1/2 clinical trial evaluating the safety, tolerability, and preliminary efficacy of invikafusp alfa as a monotherapy in biomarker-selected patients with advanced antigen-rich solid tumors, including PD-1 refractory and rare tumor types. The trial consists of two parts: Phase 1 dose escalation and Phase 2 dose expansion. For more information, visit clinicaltrials.gov (Identifier: NCT05592626).

Patients interested in participating in this study at the National Cancer Institute (NCI) can contact NCI's toll-free number: 1-800-4-CANCER (1-800-422-6237) (TTY: 1-800-332-8615), visit the website at https://trials.cancer.gov, or email [email protected].

Marengo Contacts:

Media
Peg Rusconi | [email protected] 

Investors
Svetlana Makhni | [email protected] 

SOURCE Marengo Therapeutics