Marengo to Share Updated Clinical Results from STARt-001 Phase 1/2 Clinical Trial Featuring Invikafusp Alfa Monotherapy Activity in PD1 Resistant Tumors at Upcoming AACR 2025 Clinical Plenary Oral Presentation

• Initial disease control rate of 67%, tumor regression rate of 44% and preliminary objective response rate of 22% were observed in TMB-H patients at the optimal biological dose range
  
  
• Invikafusp alfa (STAR0602) demonstrates pan-tumor selective Vβ T cell expansion in vivo across 18 different solid tumor types
  
  
• Data highlight promising anti-tumor activity as single agent in heavily pretreated anti-PD(L)1 resistant tumors including both primary and secondary resistant patients

CAMBRIDGE, Mass., April 25, 2025 /PRNewswire/ -- Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision immunotherapy, today announced an upcoming clinical plenary oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2025. The presentation will report updated clinical and translational findings from the ongoing Phase 1/2 trial (STARt-001) evaluating invikafusp alfa (STAR0602) in patients with anti-PD(L)1-resistant, antigen-rich solid tumors.

The results highlight clinical pharmacology, selective immune activation, and RP2D selection in addition to demonstrating clinically meaningful anti-tumor activity and a well-characterized safety profile. The data also further support the advancement of the lead asset into Phase 2 development and confirm clinical efficacy.

"These encouraging data represent the first clinical proof of our precision T cell agonist approach to overcome anti-PD(L)1-resistant cancer, a therapeutic area with significant unmet need. Importantly, invikafusp monotherapy not only selectively engaged and expanded a key T cell subset in immunotherapy-resistant tumors, but also reinvigorated anti-tumor responses," said Ke Liu, M.D. Ph.D., Chief Development Officer of Marengo Therapeutics. "Based on the initial disease control and tumor regression rates observed, invikafusp has the potential to offer a promising new class of immunotherapy for patients who have exhausted checkpoint inhibitor therapy options."

"The initial clinical activity of invikafusp monotherapy in PD-1 resistant tumors is novel and important as a new approach to immunotherapy," said Bruce A. Chabner, M.D., Clinical Director Emeritus at Massachusetts General Hospital. "The ability of invikafusp to activate a specific subset of T cells in heavily pretreated cancer patients and achieve objective responses in tumors that have failed PD-1 inhibitors is clinically meaningful. These results may mark the beginning of a new class of novel T cell agonists in treating checkpoint resistant cancers with precision immune activation."

Invikafusp alfa is Marengo's first-in-class, dual T cell agonist with a bi-specific antibody design to selectively activate the Vβ6 and Vβ10 subsets of T cells in vivo.

Key Findings from the Abstract (CT205):

• Initial Clinical Activity (TMB-H subgroup at optimal biologic dose):
  • Six of the initial nine efficacy evaluable patients (67%) achieved disease control (2 confirmed partial responses (cPRs) and 4 with stable disease)
  • The cPRs were in MSS colorectal cancer with one response lasting ~12 months
  • Plenary oral presentation to include updated clinical results from initial data cut and additional patients
• Clinical Pharmacology and Recommended Phase 2 Dose (RP2D):
  • RP2D was determined as 0.08 mg/kg Q2W, selected based on pharmacokinetics, pharmacodynamics, safety, and activity
  • Dose-dependent, selective expansion of peripheral CD8⁺ Vβ6/Vβ10 T cells, with ~600% average peak expansion at RP2D
  • Expanded Vβ T cells exhibited a memory phenotype and expressed cytotoxic effector molecules
  • Soluble markers of T cell activation (e.g., IFN-γ, sCD25) increased post-dosing; inflammatory cytokines (e.g., TNF-α, IL-6) remained limited below RP2D

Based on initial clinical and preclinical results, the U.S. Food and Drug Administration granted Fast Track Designation to invikafusp alfa for the treatment of patients with TMB-high colorectal cancer. The STARt-001 Phase 2 portion of the trial is ongoing and actively enrolling, focused on expanding into other antigen-rich tumors, including MSI-H and TMB-H tissue agnostic solid tumors.

Presentation Details

• Title: Updated clinical results, recommended Phase 2 dose (RP2D) determination and translational study results for START-001: a Phase 1/2 trial of invikafusp alfa, a first-in-class TCR β chain-targeted bispecific antibody in patients with anti-PD(L)1-resistant, antigen-rich solid tumors
• Abstract Number: CT205 (Late-breaking)
• Session Title: Clinical Trials Plenary: Biologics and T-cell Engagers
• Session Date and Time: Tuesday, April 29, 2025, 10:15 AM – 12:15 PM CT
• Presenter: Ryan J. Sullivan, M.D., Massachusetts General Hospital

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