On November 9, 2026 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering precision immunotherapies for oncology and inflammation and immunology (I&I), reported interim results from the Phase 1b/2 STARt-002 trial evaluating invikafusp alfa, a first-in-class dual T-cell agonist, in combination with sacituzumab govitecan-hziy (Trodelvy; SG). Results from patients with metastatic triple-negative breast cancer (mTNBC) and HR-positive/HER2-negative metastatic breast cancer (HR+/HER2− mBC) were presented in an oral session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2026 Annual Meeting.

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The presentation, titled "Initial clinical results from STARt-002: A Phase 1b/2 study of invikafusp alfa, a first-in-class dual T-cell agonist, in combination with sacituzumab govitecan in triplenegative or HR+/HER2− mBC," highlighted interim results from the first clinical trial evaluating a Vβ-directed selective T-cell agonist in combination with an antibody-drug conjugate (ADC), advancing a next-generation precision IO–ADC combination approach.

STARt-002 is evaluating the combination across two biologically distinct metastatic breast cancer populations: TNBC and HR-positive/HER2-negative disease. The combination is designed to bring together two complementary mechanisms. SG provides Trop-2-directed tumor-cell killing and antigen release, which may prime less immunogenic tumors, while invikafusp alfa selectively activates and expands functional Vβ T cells to amplify the resulting antitumor immune response.

"The interim STARt-002 findings provide encouraging evidence that invikafusp alfa retains its selective immunologic mechanism when combined with SG while generating antitumor activity across two difficult-to-treat metastatic breast cancer populations," said Steven J. Isakoff, M.D., Ph.D., Director of Breast Cancer Clinical Research at Mass General Brigham Cancer Institute and presenter of the study. "Most notably, confirmed complete responses were observed in both triple-negative and HR-positive/HER2-negative metastatic breast cancer, including a response continuing beyond one year in a patient with PD-L1-negative metastatic TNBC. These findings support further evaluation of this novel combination for patients who need new treatment options."

Highlights from the STARt-002 Presentation

As of the October 16, 2026, data cutoff, 48 patients had been enrolled across the metastatic TNBC and HR+/HER2− mBC cohorts, representing heavily pretreated populations. Fifty percent of patients had received three or more prior lines of therapy in the metastatic setting, including 67% of patients in the HR+/HER2− cohort. Key findings include:

Reductions in target lesions were observed in 71% (27/38) of efficacy-evaluable patients, with disease control achieved in 74% (28/38) overall and 83% among ADCnaïve patients across mTNBC and HR+/HER2− mBC.

Confirmed complete responses were observed in both the mTNBC and HR+/HER2− mBC cohorts, including a response continuing beyond 12 months in a patient with PDL1-negative mTNBC.

• Objective responses were observed in both breast cancer subtypes:
o 25% ORR (5/20) and 80% DCR (16/20) in HR+/HER2− mBC.
o 28% ORR (5/18) and 67% DCR (12/18) in mTNBC.
o 36% ORR (5/14) and 79% DCR (11/14) in ADC-naïve mTNBC.

Translational analyses demonstrated selective expansion of Vβ6-positive T cells in all eight patients assessed during the first treatment cycle, consistent with observations previously reported for invikafusp alfa monotherapy

The combination demonstrated a manageable safety profile consistent with the known profiles of each agent:

o Cytokine release syndrome was primarily low-grade and medically manageable.
o Adverse events commonly associated with SG were managed using established
supportive-care measures and dose modifications.
o No unexpected toxicities or treatment-related deaths were observed.

"These interim results reinforce our conviction that selective activation of Vβ T-cell populations can broaden the reach of immunotherapy, particularly in less immunogenic tumors that derive limited benefit from checkpoint inhibition," said Zhen Su, M.D., President and Chief Executive Officer of Marengo Therapeutics. "The confirmed complete responses in both metastatic breast cancer cohorts, together with reductions in target lesions in 71% of efficacy-evaluable patients, are particularly encouraging. STARt-002 is the first clinical study to combine a dual T-cell agonist with an ADC, and these data provide important clinical support for invikafusp alfa’s potential as a precision immune amplifier and IO backbone for rational combinations in broader patient populations.

The STARt-002 results highlighted here expand upon the initial Phase 2a findings presented at the 2026 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, providing a larger and more mature dataset with quantified activity across both metastatic breast cancer cohorts. The data also complement Phase 2 STARt-001 findings recently presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2026 Congress, which demonstrated tissue-agnostic, single-agent efficacy signals for invikafusp alfa across eight distinct TMB-H solid tumor types.

First-in-human data supporting this approach were recently published in Nature Medicine2 , demonstrating that invikafusp alfa can selectively activate and expand Vβ-positive T-cell populations in the blood and tumor and generate antitumor activity across advanced solid tumors. Together, STARt-001 and STARt-002 provide converging clinical and translational evidence supporting invikafusp alfa as a precision immune amplifier with potential applicability across tumor types and therapeutic combinations.

Marengo continues to advance invikafusp alfa through a focused development strategy that translates the broad potential of selective T-cell activation into prioritized programs, spanning biomarker-selected monotherapy and rational combinations in broader all-comer populations.

The use of invikafusp alfa and sacituzumab govitecan in patients with metastatic TNBC and HR+/HER2- metastatic breast cancer is investigational, and the safety and efficacy of this combination has not been established.

(Press release, Marengo Therapeutics, NOV 9, 2026, View Source [SID1234674478])