Marengo Unveils Positive First-in-Human Data for Invikafusp Alfa at 2024 SITC Meeting

Marengo Therapeutics, Inc., a clinical-stage biotechnology company focused on pioneering novel T cell activation approaches, has announced promising initial data from its Phase 1 clinical trial of invikafusp alfa (STAR0602). This data was presented during a late-breaking oral session at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in Houston, Texas.

The STARt-001 Phase 1/2 trial is the first to evaluate Marengo's innovative Vβ TCR agonist technology. The study assesses invikafusp alfa as a monotherapy in biomarker-enriched patients, specifically those with advanced anti-PD-1 resistant or refractory solid tumors. Initial Phase 1 results demonstrate early signs of anti-tumor activity and clinical benefits in heavily pre-treated cancer patients resistant to PD-1. Invikafusp alfa has also shown a manageable safety profile aligned with its novel mechanism of action, indicating its potential as a treatment across various high tumor mutation burden (TMB-H) cancers or virally associated malignancies.

Dr. Zhen Su, Chief Executive Officer of Marengo Therapeutics, expressed enthusiasm over the initial clinical findings, emphasizing the importance of the observed single-agent activity in Phase 1, particularly in PD-1 resistant tumors such as colorectal cancer. Dr. Su highlighted the significance of these results as a critical milestone, indicating the potential of STAR0602 as a foundational immuno-oncology therapy across diverse tumor types.

Key highlights from the Phase 1 findings include the sustained and selective in vivo expansion of TCRVβ6/Vβ10 T cells achieved across all six dose levels, with up to a 500% peak increase post-treatment. Disease control was observed in 50% of the 28 patients across all dose escalation cohorts, with 32% experiencing tumor shrinkage across six tumor types. At the optimal biological dose range (0.08 mg/kg and 0.12 mg/kg), invikafusp alfa demonstrated significant clinical activity with a 63% disease control rate, 50% of patients experiencing tumor shrinkage, and a 25% overall response rate in TMB-H, anti-PD-1 resistant patients.

The safety profile of invikafusp alfa was consistent with its T cell activation and expansion mechanism, with the most common treatment-related adverse events being transient grade 1 and 2 cytokine release syndrome (CRS) during the first and second infusions, without any grade 4 adverse events or immune effector cell-associated neurotoxicity syndrome (ICANS). Based on safety, pharmacokinetic/pharmacodynamic (PK/PD) data, and preliminary anti-tumor activity, a recommended Phase 2 dose of 0.08 mg/kg was selected for further studies.

Dr. James L. Gulley of the National Cancer Institute commented on the first-in-human data, noting that the novel approach of selectively activating and expanding Vβ T cell subsets shows promise for treating advanced solid tumors. The observed selective expansion of Vβ6/Vβ10 T cells across various solid tumors and the initial anti-tumor activity in heavily pre-treated anti-PD-1 resistant cancer patients with TMB-H colorectal cancer are encouraging. The differentiated clinical profile supports further investigation in subsequent clinical trials for addressing high unmet medical needs in anti-PD-1 resistant tumors.

In summary, the data from the STARt-001 study highlights the potential of invikafusp alfa as a novel therapeutic option for patients with advanced, PD-1-resistant solid tumors. Marengo Therapeutics has initiated Phase 2 dose expansion and anticipates sharing initial results in the second half of 2025.