Marengo Therapeutics has announced encouraging initial Phase 1 clinical data from its lead program, invikafusp alfa (STAR0602), at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting. The STARt-001 trial (NCT05592626) evaluated invikafusp alfa as a monotherapy in patients with advanced anti-PD-1 resistant or refractory solid tumors, enriched for biomarkers like TMB-H, MSI-H/dMMR, or viral associations.
Promising Early Clinical Activity
Phase 1 data from the STARt-001 trial demonstrated early anti-tumor activity and initial signals of clinical benefit in heavily pre-treated, anti-PD-1 resistant cancer patients. The therapy also exhibited a manageable safety profile, aligning with its novel mechanism of action. This supports its potential as a treatment option for high tumor mutational burden (TMB-H) cancers or virally associated malignancies.
Zhen Su, M.D., MBA, Chief Executive Officer of Marengo Therapeutics, stated, "The single agent activity observed in Phase 1, especially in PD-1 resistant cold tumors such as colorectal cancer is a critical milestone, and we look forward to further exploring the potential of STAR0602 to become a next-generation backbone IO therapy across a range of tumor types."
Key Phase 1 Findings
- T Cell Expansion: Sustained and selective in vivo expansion of TCRVβ6/Vβ10 T cells was achieved across all 6 dose levels, with up to ~500% peak increase post invikafusp alfa treatment.
- Disease Control: A Disease Control Rate (PR + SD) was reported in 50% of 28 patients from all dose escalation cohorts, with 32% of patients experiencing tumor shrinkage across six tumor types.
- Optimal Biological Dose: At the optimal biological dose range (0.08 mg/kg and 0.12 mg/kg), invikafusp alfa demonstrated single agent clinical activity with a 63% Disease control rate, 50% of patients experienced tumor shrinkage and 25% ORR reported in TMB-H, anti-PD-1 resistant patients.
- Safety Profile: The safety profile was consistent with the T cell activation/expansion mechanism of action (MOA) without corticosteroid or tocilizumab pretreatment. The most common treatment-related adverse events (TRAEs) were mainly transient grade 1 & 2 CRS during first and second infusion without any grade 4 adverse events (AEs) or immune effector cell-associated neurotoxicity syndrome (ICANS).
- Recommended Phase 2 Dose: Recommended Phase 2 dose (RP2D) of 0.08 mg/kg was selected for Phase 2 dose expansion studies based on safety, PK/PD data and preliminary anti-tumor activity.
Expert Commentary
Dr. James L. Gulley, Co-Director of the Center for Immuno-Oncology and Clinical Director of the National Cancer Institute, commented, "The first-in-human data suggest that this novel approach to selectively activate and expand Vβ T cell subsets may hold promise for treating patients with advanced solid tumors... The differentiated clinical profile supports further investigation of this unique mechanism of action in the next phase of clinical trials for high unmet medical needs in anti-PD-1 resistant tumors."
STAR Platform and Invikafusp Alfa
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. Invikafusp alfa (STAR0602) selectively targets a common Vβ T cell subset present in all cancers and, by combining a novel non-clonal mode of TCR activation with a T cell co-stimulator in the same molecule, promotes expansion of a new population of clonally enriched, effector memory Vβ T cells that turbo-charge tumor immune responses and promote durable clearance of tumors.
Ongoing and Future Development
Marengo has initiated the Phase 2 dose expansion of the STARt-001 study and expects to share initial results in 2H 2025. The data presented from the STARt-001 study underscore invikafusp alfa's potential as a novel therapeutic option for patients with advanced, PD-1-resistant solid tumors.
