invikafusp alfa (STAR0602) / Marengo - LARVOL DELTA

START-001: Phase 2 results of invikafusp alfa, a first-in-class T cell receptor β-chain–targeted bispecific antibody, as monotherapy in patients with TMB-H solid tumors resistant to immune checkpoint blockade (ICB) (ESMO 2026) - No abstract available

Bispecific • Checkpoint block • Checkpoint inhibition • Clinical • Monotherapy • P2 data • Oncology • Solid Tumor • TMB

Initial monotherapy clinical activity of invikafusp alfa, a first-in-class TCR β-chain-targeted bifunctional antibody, in tissue-agnostic, TMB-H patients from STARt-001, a Phase 1/2 trial (SITC 2025) - P1/2 | "The list of the names of the ethics committee(s) or institutional review board(s): Comite de Protection des Personnes Sud-Est III (CT # 2023-505334-10-01) CEIm HM Hospitales (CT # 2023-505334-10-01) Dana Farber Cancer Institute IRB (22-577) Comite de Protection des Personnes Sud-Est III (CT # 2023-505334-10-01) Institutional Review Board/Privacy Board/Memorial Sloan Kettering Cancer Center (23-239) CEIm HM Hospitales (CT # 2023-505334-10-01) WCG IRB (Inst Tracking #: NCT05592626) University of Miami Human Subject Research Office (HSRO) (IBIS# 20231136) NIH Office of IRB Operations (23-5345) AdventHealth Orlando IRB (2052490-3) WCG IRB (Inst Tracking #: STUDY00019146) WCG IRB (Inst. Tracking #: 24-11-7340)Abstract 1316 Table 1View inline•Open as popupInvikafusp showed tissue-agnostic anti-tumor activity (partial responses and tumor regression) in 10 different tumor types with high tumor mutational burden (TMB-H*)"

Clinical • IO biomarker • Late-breaking abstract • Monotherapy • P1/2 data • Pan tumor • Tumor mutational burden • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • FOXP3 • IL2 • MSI • PD-1 • TMB

START001: a phase 1/2 study of invikafusp alfa (STAR0602), a first-in-class TCR β chain-targeted bispecific antibody, as monotherapy in patients with antigen-rich solid tumors resistant to anti-PD(L)1 (SITC 2024) - P1/2 | "All patients experienced grade 1 fever and 60% had grade 2 CRS without premedication with corticosteroids or tocilizumab. Advent Health (Central Florida) IRB. ID of the approval:2052490-3."

Clinical • Late-breaking abstract • Monotherapy • P1/2 data • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • CD4 • CD8 • MSI • TMB

Trial START-001: A phase 1/2 study of STAR0602, a first-in-class, selective T cell receptor (TCR)-targeting, bifunctional antibody-fusion molecule, as monotherapy in patients with antigen-rich tumors post checkpoint inhibitor (CPI) treatment. (ASCO 2023) - P1/2 | "Phase 1 enrollment has begun since January 2023. Clinical trial information: NCT05592626."

Checkpoint inhibition • Clinical • IO biomarker • Monotherapy • P1/2 data • Tumor mutational burden • Breast Cancer • Cervical Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Merkel Cell Carcinoma • Microsatellite Instability • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Oropharyngeal Cancer • Ovarian Cancer • Prostate Cancer • Refractory Ovarian Cancer • Skin Cancer • Solid Tumor • Triple Negative Breast Cancer • Vulvar Cancer • CD4 • CD8 • IL2 • KRAS • MSI • TMB

Marengo Therapeutics…announced the completion of enrollment in the monotherapy cohorts of STARt-001, its Phase 1/2 clinical trial evaluating invikafusp alfa in patients with PD-1–resistant, antigen-rich solid tumors (PRNewswire) - "Enrollment continues in standard of care combination cohorts. In addition, updated results from the study have been selected for an oral presentation at the European Society for Medical Oncology (ESMO) 2026 Congress, taking place October 23–27 in Madrid, Spain....Following the ESMO presentation, the company expects to complete planned interactions with the U.S. Food and Drug Administration (FDA) to align on the development plan for invikafusp alfa, with the next stage of development expected to begin in 2027."

Enrollment status • FDA event • P1/2 data • Pipeline update • Solid Tumor

Phase I/II 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 (ESMO-GI 2025) - P1/2 | "Invikasfusp, a first-in-class selective, dual T cell agonist, as monotherapy, led to clinically meaningful anti-tumor activity in various GI cancers, particularly in CRC. The Phase 2 expansion is ongoing in antigen-rich GI tumors to further investigate the efficacy of invikafusp in these cancers."

Clinical • Monotherapy • P1/2 data • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • CD8 • MSI • TMB

START-001: A Study of a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule STAR0602 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=366 | Recruiting | Sponsor: Marengo Therapeutics, Inc. | Trial completion date: Oct 2026 ➔ Sep 2027 | Trial primary completion date: Oct 2026 ➔ Sep 2027

First-in-human • Trial completion date • Trial primary completion date • Colorectal Cancer • Epstein-Barr Virus Infections • Genito-urinary Cancer • Gynecologic Cancers • Infectious Disease • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urology • Vulvar Cancer • MSI • TMB

Marengo Therapeutics…announced that key Phase 2 data from the ongoing STARt-001 study of invikafusp alfa, a first-in-class bispecific dual T-cell agonist, have been selected for an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2026 (PRNewswire) - "The ESMO presentation will feature updated clinical and translational data from tumor mutational burden-high (TMB-H) patients with advanced solid tumors that are refractory or resistant to PD-1–directed therapy."

P2 data • Solid Tumor

PARP inhibition combined with a T-cell receptor β chain-directed antibody fusion molecule drives polyclonal antitumor immunity and tumor regression. (PubMed, J Immunother Cancer) - P1/2 | "These findings suggest that combining tumor-sensitizing therapies with selective T-cell activation may represent a broader strategy to overcome immune exclusion in solid tumors. Together, these results provide mechanistic rationale for clinical evaluation of olaparib in combination with STAR0602 in patients with mCRPC who have progressed on androgen deprivation therapy."

IO biomarker • Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • CD8 • IFNG • IL2 • TNFRSF10B

Docetaxel enhances Vβ-directed T-cell activation and antitumor immunity mediated by a bifunctional TCR agonist in breast and prostate cancer models. (PubMed, Front Immunol) - "These findings identify a mechanistic axis in which docetaxel-induced tumor sensitization via TRAIL-R2 cooperates with Vβ-targeted T cell expansion to drive coordinated immune-mediated tumor regression. This work supports the clinical evaluation of STAR0602 in combination with chemotherapy and highlights TRAIL-R2-mediated tumor sensitization as a mechanistically defined strategy to enhance immunotherapy efficacy in immune-excluded tumors."

IO biomarker • Journal • Preclinical • Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8 • IL2 • TNFRSF10B

Initial clinical and translational results and selection of recommended phase 2 dose (RP2D) 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 metastatic triple-negative or HR+/HER2- breast cancer (AACR 2026) - "This first-in-human study demonstrates 1) the feasibility and safety of invika, a FIC dual T-cell agonist, in combination with SG, a standard-of-care ADC; 2) dose-dependent expansion of Vβ6 T cells; 3) antitumor activity, including confirmed responses, in heavily pre-treated mBC patients. Phase 2 expansion is ongoing to further study the efficacy and safety of this novel combination in patients with mBC."

Clinical • Combination therapy • First-in-human • Metastases • P1/2 data • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Marengo Reports Late-Breaking Initial Phase 2 Clinical Results from Invikafusp Alfa Plus TRODELVY and Unveils Partnered Novel IPN01203/STAR0501 STAR Program in Phase 1 at AACR 2026 (PRNewswire) - "To date, invikafusp alfa with TRODELVY has shown a safety profile consistent with the known profiles of the individual agents. Pharmacodynamic analyses further confirmed that invikafusp alfa maintains its mechanism of action in a combination regimen, driving robust and selective expansion of Vβ6/Vβ10 T cells. The STARt-002 Phase 1b/2a trial is actively enrolling patients at select cancer centers across North America, with enrollment expected to be completed later this year....The next clinical candidate, IPN01203/STAR0501, has been selected for an oral presentation during the New Drugs on the Horizon session."

Late-breaking abstract • P1/2 data • Pipeline update • Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Solid Tumor • Triple Negative Breast Cancer

Docetaxel enhances anti-tumor activity of bi-functional TCR activating molecule in breast and prostate cancer models [WITHDRAWN] (AACR 2025) - "Here, we show that combining mSTAR1302 with docetaxel resulted in enhanced anti-tumor activity compared to either single agent alone, demonstrating an increased efficacy in cold tumor models such as 4T1 and TRAMP-C2. The data provide the groundwork for the clinical development of docetaxel and STAR0602 as a combination therapy."

IO biomarker • Preclinical • Breast Cancer • Genito-urinary Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8 • IL2 • TNFRSF10B

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 b chain-targeted bispecific antibody in patients with anti-PD(L)1-resistant, antigen-rich solid tumors (AACR 2025) - "Invikafusp, a selective, dual T cell agonist, as monotherapy, led to clinically meaningful anti-tumor activity in anti-PD(L)-1 resistant tumors. It promoted potent and selective expansion of mainly CD8+ Vβ6/ Vβ10 T cells with a novel TCM phenotype, and ledto ctDNA decrease and expansion of antigen-specific T cells. Based on these initial clinical results, US FDA granted Fast track Designation for invikafusp in TMB-H CRC and a Phase 2 trial is ongoing in antigen-rich (e.g., TMB-H & MSI-H/dMMR) tumors."

Bispecific • Clinical • P1/2 data • P2 data • Colorectal Cancer • Esophageal Cancer • Melanoma • Microsatellite Instability • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • IFNG • IL6 • MSI • TMB • TNFA

Epigenetic modulation synergizes with a novel TCR β chain directed antibody-fusion molecule to suppress checkpoint-refractory tumors irrespective of MHC I status (AACR 2024) - "Ongoing mechanistic studies indicate combination therapy to elicit complimentary mechanisms of tumor suppression beyond CD8+ T cells. Ongoing proteomic and single-cell transcriptomic investigation of MHC-I competent and null tumors will provide a deeper insight into the mode of action of this combination therapy. Collectively, these data support the use of STAR0602 in combination with Entinostat for the treatment of solid malignancies, including for patients harboring ICB-refractory tumors devoid of MHC class I."

Colon Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • B2M • CD4 • CD8 • IFNG • KRAS

Clinical Experience of Invikafusp Alfa, a Selective Dual T-cell Agonist (SITC-SSC 2026) - No abstract available

Clinical

Synergistic epigenetic modulation with a TCRβ-targeted IL-2 fusion molecule enhances CD8 + T cell-mediated MHC-I independent tumor control via an antibody-linked mechanism (AACR-IO 2026) - "Here, we examined the tumor-suppressive ability and mode of action of a murine surrogate of STAR0602 (mSTAR1302), which targets murine TCRVβ13.2/13.3, in combination with the class I HDAC inhibitor (HDACi) Entinostat, an epigenetic modulator that enhances tumor immune cell recognition, in multiple ICB-refractory tumor models devoid of MHC-I. Collectively, these data highlight an alternative mechanism of tumor suppression when direct MHC-I/TCR engagement is absent. This supports the use of STAR0602 in combination with HDAC inhibitors for the treatment of solid malignancies including those resistant to current ICB therapies. Citation Format: Katherine L. Lothstein, Lisa K. Poppe, Christine M. Minnar, Asma S. Khelifa, Ainara Meler, Nicholas Roller, Masaya Miyamoto, David Peeney, Andrew Bayliffe, Zhen Su, James L. Gulley, Jeffrey Schlom, Sofia R. Gameiro."

Colorectal Cancer • Oncology • Solid Tumor • B2M • CD4 • CD8 • FCGR3A • IL2 • IL2RA • TRB

A novel TCRβ-directed IL-2 fusion molecule promotes stem-like CD8 + T cells with self-renewing properties in the peripheral lymphoid tissue, further expanded by HDAC inhibition to elicit a sustained anti-tumor therapeutic response (AACR-IO 2026) - "Collectively, these data demonstrate the antitumor effects of non-canonical TCRVβ13/IL-2R targeting to be significantly augmented by combination with Entinostat. These effects are associated with TCRVβ13/IL-2R targeting augmenting CD8 + T cell self-renewal properties, further enhanced with HDACi combination. Collectively, this data supports the clinical use of STAR0602 in combination with HDAC inhibitors for patients harboring solid malignancies irrespective of ICB sensitivity."

Oncology • Solid Tumor • CD4 • CD8 • IL2 • IL2RA • KRAS • TRB

Examination of a novel bi-functional TCR activating molecule in combination with docetaxel in breast and prostate cancer models (AACR-IO 2026) - "Background STAR0602 is a novel bi-functional T-cell engager comprised of an antibody targeted to Vβ6/Vβ10 T-cell receptors conjugated to interleukin-2 that is currently being evaluated in clinical trials. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B020."

Combination therapy • IO biomarker • Preclinical • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8 • FASLG • IL2 • TNFRSF10B

Combination therapy with a TCR Vβ-directed bifunctional molecule, cisplatin and anti-PD-1 promotes antitumor activity in immune checkpoint blockade-refractory head and neck murine tumor models (AACR-IO 2026) - "Background Immune checkpoint blockade (ICB) treatment, alone or in combination with cisplatin and fluorouracil (FU) chemotherapy, is used as first-line treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)...STAR0602, a selective, bifunctional T cell agonist consisting of an antibody targeting Vβ6 and Vβ10 T cell receptors fused to human interleukin-2, has demonstrated clinical activity in anti-PD(L)-1 resistant tumors...In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A028."

Checkpoint block • Checkpoint inhibition • Combination therapy • IO biomarker • Preclinical • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • IFNG • IL2

A phase 1b/2 clinical investigation of invikafusp alfa (STAR0602), a first-in-class dual T-cell agonist, in combination with sacituzumab govitecan in patients with metastatic TNBC or HR+/HER2- MBC (START-002 trial) (SABCS 2025) - P1/2 | "Recent clinical results from the ASCENT-04 trial demonstrated improved progression-free survival in previously untreated PD-L1+ mTNBC patients who received the combination of SG and pembrolizumab, thus confirming the clinical potential of combining an ADC with an IO agent in metastatic breast cancer.START-002 explores the hypothesis that combining SG's immunomodulatory potential with invikafusp alfa's selective activation and expansion of tumor-reactive Vβ6/Vβ10 T-cells, will enhance anti-tumor responses and result in improved clinical outcomes in breast cancer patients.Study design: START-002 is a phase 1b/2 open label, multi-center study to determine the safety, feasibility, and anti-tumor activity of invikafusp alfa in combination with SG in patients with mTNBC or HR+/HER2- mBC. Prior topoisomerase 1 inhibitor therapy is excluded.Primary objective and endpoint: The primary objective of this Ph1b/2 study is to characterize the safety and tolerability of..."

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Tumor mutational burden • Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer • CD8 • HER-2 • PD-L1 • TMB

Initial clinical and pharmacology results from START-002: A phase 1b/2 clinical investigation of invikafusp alfa (STAR0602), a first-in-class dual T cell agonist, in combination with sacituzumab govitecan in patients with mTNBC or HR+/HER2- mBC (SABCS 2025) - "Invika in combination with SG is feasible and safe at the doses tested. Combination safety profile is consistent with the known safety profile of each individual agent. Consistent with its mechanism of action, invika demonstrated unequivocal expansion of Vβ6/10 T cells when given with SG in mBC patients."

Clinical • Combination therapy • IO biomarker • P1/2 data • Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer • CD8 • HER-2 • TMB

Marengo to Present Initial Results from Invikafusp Alfa and TRODELVY Combination Study, STARt-002, at the 2025 San Antonio Breast Cancer Symposium (PRNewswire) - "Early anti-tumor activity observed in majority of patients, recommended dose selected for phase 2 expansion cohorts currently enrolling at select North American cancer centers..Early findings from the combination study of Invikafusp alfa (Invika) and TRODELVY (sacituzumab govitecan-hziy; SG) suggest that this novel regimen, which leverages two key modalities (immunotherapy and ADCs), is well tolerated and biologically active across all dose levels evaluated. The safety profile of the combination was consistent with the known profiles of each agent...Pharmacodynamic analyses confirmed that Invika maintains its mechanism of action in combination with Trodelvy, inducing robust and selective expansion of Vβ6/10 T cells in patients with previously treated metastatic triple-negative breast cancer (TNBC) and HR+/HER2– metastatic breast cancer."

P1/2 data • Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer

Initial clinical and pharmacology results from START-002: A phase 1b/2 clinical investigation of invikafusp alfa (STAR0602), a first-in-class dual T cell agonist, in combination with sacituzumab govitecan in patients with metastatic TNBC or HR+/HER2- MBC [WITHDRAWN] (SABCS 2025) - No abstract available

Clinical • Combination therapy • Metastases • P1/2 data • Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer • HER-2

Marengo Late-Breaking Oral Presentation Highlights Single-Agent, Pan Tumor Activity of Invikafusp Alfa Across PD-1-Resistant Cancers in Phase 2 Clinical Trial at SITC 2025 (PRNewswire) - "As of the July 15, 2025 data cutoff, 57 patients with TMB-H advanced solid tumors were enrolled across 20 histologies and 46 patients were efficacy-evaluable....20% ORR and 80% DCR observed across seven major tumor types - colorectal, gastric, lung, breast, GEJ, head and neck, and bladder cancers. Responses by indication include gastrointestinal (GI) tumors (28% ORR, 78% DCR), colorectal cancer (CRC) (33% ORR, 67% DCR), and non-small cell lung cancer (NSCLC) (20% ORR, 80% DCR). Target tumor shrinkage, with 59% of patients experiencing target-lesion regression."

Late-breaking abstract • P2 data • Bladder Cancer • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastroesophageal Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer