invikafusp alfa (STAR0602) / Marengo - LARVOL DELTA

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

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

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

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

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

A novel TCRβ-directed IL-2 fusion molecule promotes memory CD8+ T cells with self-renewing properties in tumor ecosystems, further expanded by HDAC inhibition to elicit effective tumor suppression (SITC 2025) - "Here, we examined the tumor-suppressive ability and mode of action of a murine surrogate of STAR0602 (mSTAR1302), which targets the prevalent murine TCRVβ13.2/13.3, in combination with the class I HDAC inhibitor (HDACi) Entinostat, an epigenetic modulator that enhances tumor immune recognition, in multiple tumor models irrespective of ICB responsiveness.Methods mSTAR1302 and/or Entinostat were administered to mice bearing ICB-responsive breast (EMT6) and ICB-refractory colorectal (CT26; KRasG12Dmut) tumors. 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 • IFNG • IL2 • IL2RA • KRAS • TRB

Docetaxel enhances the anti-tumor activity of a novel bi-functional TCR activating molecule in breast and prostate cancer models (SITC 2025) - "Lastly, combination treatment led to a significant increase in AH1 antigen-specific T-cells in the 4T1 model.Conclusions Here, we show that combining mSTAR1302 with docetaxel resulted in enhanced anti-tumor activity compared to either single agent alone showing an increased efficacy in cold tumor models such as 4T1 and TRAMP-C2. This data provides groundwork for the clinical development of docetaxel and STAR0602 as a 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

Triple combination therapy with a TCR Vb-directed bifunctional molecule, cisplatin and anti-PD-1 in immune checkpoint blockade-refractory head and neck murine tumor models (SITC 2025) - "Background Immune checkpoint blockade (ICB) treatment, alone or in combination with standard anti-cancer therapies, has led to important progress in the treatment of head and neck squamous cell carcinoma (HNSCC). The combination of mSTAR1302 and α-PD-1 enabled control of tumors that progressed following platinum-containing treatment.Conclusions These findings provide a rationale for the combination of STAR0602 and SOC therapy in the clinical setting for patients with recurrent or metastatic HPV- HNSCC.Ethics Approval All animal experimental studies were performed under the approval of the NIH Intramural Animal Care and Use Committee. All mice were housed and maintained in accordance with the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) guidelines: NIH AALAC approval: CIO-2."

Checkpoint block • Checkpoint inhibition • Combination therapy • IO biomarker • Preclinical • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • IFNG • IL2 • PD-1

A novel anti-TCR Vb targeted bispecific antibody in combination with a poly ADP-ribose polymerase inhibitor (PARPi) enhances anti-tumor immune response in prostate cancer models (SITC 2025) - P1/2 | "Our study tested the hypothesis that combination of mSTAR1302, the murine surrogate of STAR0602, with Olaparib, will achieve a robust anti-tumor efficacy in prostate cancer models.Methods Using TRAMP-C2 and RM-1, both syngeneic murine prostate cancer models classified as immunologically 'cold' tumors, we assessed anti-tumor activity and survival benefit after combination therapy. This data strongly supports the rationale for the design of clinical trials in mCRPC using combination therapy.Ethics Approval All animal studies were performed according to approved NIH Intramural Animal Care and Use Committee protocol (CIO-02). All mice were housed and maintained in accordance with the Association for Assessment and Accreditation of Laboratory Animal Care guidelines."

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

Epigenetic modulation synergizes with TCRβ-targeted IL-2 to yield CD8+ T cell dependent, MHC-I independent tumor control via an antibody associated mechanism (SITC 2025) - "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.Methods mSTAR1302 and/or Entinostat were administered to mice bearing β2-microglobulin (B2m)-deleted (MHC-Inull) breast (EMT6) and colorectal (MC38) tumors. Ongoing mechanistic investigation of this myeloid/lymphoid crosstalk in MHC-I+ and MHC-Inull tumors will provide deeper insight into the mode of action of this combination therapy.Conclusions 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."

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

Impact of a Vβ6/Vβ10 targeting IL-2 fusion protein (invikafusp alfa) on the peripheral immunome, including stimulation of memory T cells with self-renewing properties, in patients with cancer (SITC 2025) - P1/2 | "Further studies combining STAR0602 with other immunotherapeutic agents to synergize with this peripheral burst of T cell stemness are warranted.Ethics Approval All subjects gave written informed consent. Study protocol (NCT05592626) was approved by the NIH's IRB, and conducted in accordance with institutional and federal guidelines."

Clinical • Colorectal Cancer • Oncology • Solid Tumor • CD4 • CD8 • GZMB • IL2 • IL2RA • PD-1

Marengo Presents Initial Phase 2 Results Demonstrating Broad Single-Agent Activity of Invikafusp Alfa Across Multiple PD-1-Refractory or -Resistant Solid Tumors as a Late-Breaking Oral Presentation at ESMO 2025 (PRNewswire) - "As of the July 29, 2025 data cutoff, 55 patients with advanced solid tumors....Tumor shrinkage: 52% of patients experienced target-lesion regression. In the TMB-H patients, there was a 20.5% overall response rate (ORR) (9/44) and a 79.5% disease control rate (DCR) (35/44) across six tumor types, including colorectal, gastric, lung, breast, GEJ, and head and neck cancers. In the MSI-H/dMMR patients, there was a 30% ORR (3/10) and 70% DCR (7/10)."

dMMR • Late-breaking abstract • MSI-H • P2 data • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer

START-001: Initial phase II clinical activity of invikafusp alfa, a first-in-class T cell receptor (TCR) β-chain-targeted bispecific antibody as monotherapy in patients with antigen-rich solid tumors resistant to immune checkpoint blockade (ICB) (ESMO 2025) - P1/2 | "Conclusions As a first-in-class, dual T cell agonist, invikasfusp monotherapy led to clinically meaningful anti-tumor activity in TMB-H tumors with potential to overcome ICB resistance (particularly in NSCLC and CRC) offering a new class of IO backbone option for these patients. Phase 2 expansion is ongoing to further investigate the efficacy of invikafusp."

Checkpoint block • Checkpoint inhibition • Clinical • Late-breaking abstract • Monotherapy • P2 data • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • MSI • PD-L1 • TMB

Marengo to Present Late-Breaking Clinical Oral Abstract at SITC 2025 Highlighting Initial Monotherapy Activity of Invikafusp Alfa in Tissue-Agnostic, TMB-High Advanced Cancers (PRNewswire) - "The presentation will include initial Phase 2 monotherapy results from the ongoing STARt-001 trial, which is evaluating Invikafusp alfa in tissue-agnostic, tumor mutational burden-high (TMB-H) advanced cancers....Marengo will also present data from its TriSTAR T cell engager platform in addition to four preclinical analyses in collaboration with the National Cancer Institute (NCI) exploring rational combinations of Invikafusp alfa with standard-of-care modalities."

Late-breaking abstract • P2 data • Preclinical • Solid Tumor

Marengo Therapeutics to Present Key Pipeline Updates at 2025 SITC Annual Meeting and Reveal First Asset from TriSTAR Platform Targeting Nectin-4 (PRNewswire) - "...for the first time present preclinical data on its lead TriSTAR program, TriSTAR0701....The company will feature four preclinical presentations in partnership with NCI evaluating rational combination strategies for Invikafusp alfa, the company's lead clinical-stage program, with standard-of-care agents including immune checkpoint blockade (ICB), chemotherapies, HDAC inhibitors, and PARP inhibitors."

Preclinical • Head and Neck Cancer • Prostate Cancer

Combination of a novel TCR Vβ chain-directed selective T cell activator with standard of care therapy for head and neck cancer improves antitumor responses and promotes regression of checkpoint-refractory tumor models. (PubMed, J Immunother Cancer) - "These findings provide a rationale for the combination of STAR0602 and SOC therapy in the clinical setting for patients with recurrent or metastatic HPV- HNSCC."

IO biomarker • Journal • Preclinical • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • IFNG • IL2

Marengo to Present a Late-breaking Clinical Oral Abstract at ESMO 2025 on Initial Phase 2 Clinical Data of Invikafusp Monotherapy Activity in Patients with Antigen-Rich Solid Tumors Resistant to Immune Checkpoint Blockade (PRNewswire) - "Data to be presented from the STARt-001 trial demonstrating invikafusp's single-agent anti-tumor activity in diverse, large cancer indications."

Late-breaking abstract • P2 data • Solid Tumor

Marengo Therapeutics, Inc…announced the completion of the safety run-in and the determination of recommended Phase 2 dose (RP2D) for its ongoing Phase 1b/2 STARt-002 trial. (Marengo Press Release) - "The study, evaluating Marengo’s dual T-cell agonist invikafusp alfa in combination with TRODELVY (sacituzumab govitecan-hziy), Gilead’s approved TROP2-directed antibody-drug conjugate (ADC), is now advancing into two expansion cohorts in HR+/HER2− and TNBC metastatic breast cancer, respectively...The STARt-002 study (NCT06827613) is currently enrolling patients across leading North American cancer centers..."

Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer

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

Marengo Presents Monotherapy Activity of Invikafusp Alfa, a First-in-Class Selective Dual T Cell Agonist in PD-1 Resistant GI Tumors, as a Late-Breaking Oral Presentation at ESMO Gastrointestinal Cancers Congress 2025 (PRNewswire) - P1/2 | N=365 | START-001 (NCT05592626) | Sponsor: Marengo Therapeutics, Inc. | "Marengo Therapeutics...presented new clinical data from the ongoing STARt-001 Phase 1/2 trial of Invikafusp alfa...Updated Findings from the ESMO GI 2025 Clinical Plenary Presentation: In 17 heavily pretreated PD-1 resistant TMB-H GI cancer patients, invikafusp alfa monotherapy demonstrated: Disease control rate (DCR): 63%; Tumor Regression Rate of 53%; Overall response rate (ORR): 23%...Responses included: Three CRC responders across major molecular subtypes (MSS RASwt, MSS RASmut, PD-1 resistant MSI-H); One objective response in PD-1 resistant MSI-H GEJ; In PD-1 resistant TMB-H metastatic CRC specifically, ORR was 25% (3/12 patients)...No new safety signals observed in Phase 2a; Safety profile consistent with invikafusp alfa's selective T cell activation mechanism; Adverse events were generally transient and manageable with supportive care."

MSI-H • P1/2 data • Colorectal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Microsatellite Instability

Phase 2 dose expansion of START-001: A phase 1/2 study of invikafusp alfa (STAR0602), a first-in-class, selective T cell receptor (TCR)-targeting, bifunctional antibody-fusion molecule, as monotherapy in patients with antigen-rich tumors resistant to anti-PD(L)-1. (ASCO 2025) - P1/2 | "Primary endpoint: overall response rate (ORR) per iRECIST. The enrollment to the first three cohorts has begun."

Clinical • IO biomarker • Monotherapy • P1/2 data • P2 data • Breast Cancer • Castration-Resistant Prostate Cancer • Cervical Cancer • Colorectal Cancer • Epithelial Ovarian Cancer • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Microsatellite Instability • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Oropharyngeal Cancer • Ovarian Cancer • Prostate Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Triple Negative Breast Cancer • Vulvar Cancer • CD8 • MSI • TMB

Marengo Appoints Dr. Everett Vokes to the Scientific Advisory Board While Advancing Invikafusp alfa Clinical Program in PD-1 Resistant Solid Tumors (PRNewswire) - "Following our recent data presented at AACR showing pan-tumor activity of Invikafusp alfa in multiple solid tumors that are resistant to PD-1 treatment, Dr. Vokes' deep expertise and leadership in the landscape of clinical cancer research, specifically in thoracic oncology, will be instrumental in shaping our development strategy. His insight will not only help advance invikafusp as a next generation pan-tumor IO backbone but will also provide broader guidance as we progress our expanding pipeline."

Commercial • Solid Tumor

Marengo Doses First Patient in STARt-002 Clinical Trial Evaluating First-in-Class Dual T Cell Agonist, Invikafusp Alfa in Combination with TROP2-directed ADC Trodelvy in Metastatic Breast Cancer (PRNewswire) - "Marengo Therapeutics...today announced that the first patient has been dosed in its STARt-002 clinical trial. The Phase 1b/2 study evaluates the safety and efficacy of Marengo's lead clinical T cell agonist in combination with Trodelvy (sacituzumab govitecan-hziy), Gilead's approved TROP2-directed antibody-drug conjugate (ADC), in patients with metastatic breast cancer (mBC)...beginning with a run-in phase to determine the optimal tolerated combined dose of the two agents, followed by dose expansion in two patient cohorts: metastatic triple-negative breast cancer (mTNBC) and hormone receptor-positive, HER2-negative (HR+/HER2−) metastatic breast cancer."

Trial status • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Triple Negative Breast Cancer