On April 29, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision immunotherapy, reported new clinical and translational data from the ongoing STARt-001 Phase 1/2 trial of invikafusp alfa (STAR0602), presented as a clinical plenary oral session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Marengo Therapeutics, APR 29, 2025, View Source [SID1234652333]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The presentation highlights strong evidence of meaningful clinical activity, robust immune activation in vivo, and a well-characterized safety profile, further supporting the momentum behind the ongoing Phase 2 study as well as the value proposition for developing invikafusp as monotherapy in PD1 resistant TMB-H cancers.

"Today’s data represent a major step forward for Marengo and for the field of IO to advance a new class of cancer immunotherapy: Immune Activation Inducers (IAI)," said Zhen Su, M.D., M.B.A., Chief Executive Officer of Marengo Therapeutics. "Invikafusp alfa’s ability to selectively activate and expand a key T cell subset to drive meaningful anti-tumor responses across a range of PD-1 resistant tumors gives us confidence in our precision T cell activation approach. The emerging clinical signals in both colorectal and lung cancers further underscore invikafusp’s pan-tumor potential and justify our focused expansion into these high-need indications."

"Colorectal cancer is less sensitive to immunotherapy except in a very small percentage of MSI-H tumors. The field has seen few, if any, immunotherapy agents achieve single-agent activity in PD-1 resistant colorectal cancer," said Josep Tabernero, M.D., Director of Vall d’Hebron Institute of Oncology (VHIO). "The clinical signals observed with invikafusp alfa in both CRC and other tumor types are highly encouraging and warrant further clinical investigation to fully realize the clinical potential of this novel T cell agonist approach."

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.

Updated Findings from the STARt-001 Clinical Plenary Presentation:

Clinically meaningful anti-tumor activity as monotherapy in anti-PD(L)1-resistant tumors at the recommended Phase 2 dose (RP2D) of 0.08 mg/kg:
61% disease control rate in heavily pretreated, PD-1 resistant tumors dosed at 0.08 or 0.12 mg/kg
52% tumor regression rate observed across multiple tumor types, including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), cervical, squamous cell carcinoma of the head and neck (SCCHN), and melanoma
Objective responses in colorectal cancer and NSCLC:
3 responders out of 10 TMB-high metastatic CRC patients (across RAS wild-type, RAS mutant, and MSI-H subtypes)
1 additional responder with 73% tumor regression out of 2 anti-PD(L)1-resistant TMB-high NSCLC patients
Mechanism of Action and Translational Insights:
Invikafusp promoted potent, selective expansion of peripheral CD8+ Vβ6/Vβ10 T cells, which acquired a novel "memory-like effector" phenotype in both blood and tumor tissue
Expanded and activated Vβ T cells in post treatment tumor tissues consistent with enhanced anti-tumor function
Safety Profile:
Consistent with a selective T cell activation mechanism
Adverse events were generally transient and manageable with supportive care
Based on these early clinical and preclinical findings, the U.S. Food and Drug Administration has granted Fast Track Designation to invikafusp alfa for the treatment of patients with TMB-high colorectal cancer.

The Phase 2 portion of the STARt-002 trial is actively enrolling patients across multiple tumor types, including TMB-H metastatic colorectal cancer, MSI-H and TMB-H tissue-agnostic solid tumors.