On April 25, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision immunotherapy, reported an upcoming clinical plenary oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Marengo Therapeutics, APR 25, 2025, View Source [SID1234652161]). 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.

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 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