FDA Grants Fast Track Designation to Invikafusp Alfa in TMB-H Colorectal Cancer

• Invikafusp alfa (STAR0602) received fast track designation for treating advanced high tumor mutation burden (TMB-H) colorectal cancer.
• Early studies demonstrated invikafusp alfa’s antitumor activity in heavily pretreated patients, with a favorable safety profile and minimal severe adverse events (AEs).
• The recommended phase 2 dose of 0.08 mg/kg was selected based on safety and efficacy data, with ongoing trials exploring its potential as a novel therapeutic for PD-1–resistant cancers.

The FDA has granted fast track designation to invikafusp alfa, a first-in-class selective dual T-cell agonist, for the potential treatment of patients with advanced colorectal cancer with TMB-H.¹

Findings from a first-in-human, phase 1 study of the agent in heavily pretreated patients with cancer support this designation. The results, which were presented at the 2024 Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting, as well as during an oral presentation at the 2024 ESMO Immuno-Oncology Congress, showed the antitumor activity observed with invikafusp alfa. The agent also demonstrated a favorable safety profile.

In biomarker-enriched, heavily pretreated patients with advanced anti–PD-1 resistant or refractory solid tumors, invikafusp alfa demonstrated early antitumor activity, with sustained and selective in vivo expansion of TCRVβ6/Vβ10 T cells observed across all 6 dose levels, peaking at ~500%.² Among 28 patients in dose-escalation cohorts, the disease control rate (DCR) was 50%, with tumor shrinkage observed in 32% across 6 tumor types. Notably, at the optimal biological dose range of 0.08-0.12 mg/kg, invikafusp alfa showed single-agent clinical activity, achieving a 63% DCR, 50% tumor shrinkage, and a 25% objective response rate (ORR) in patients with TMB-H and anti–PD-1-resistant disease.

Colorectal cancer image: © mi_viri - stock.adobe.com

"The FDA's fast track designation is an important milestone for the STAR0602 program and further positions our unique selective dual T-cell agonist platform as a promising solution to address key challenges that perpetuate significant unmet needs in oncology," said Zhen Su, MD, MBA, chief executive officer of Marengo Therapeutics, in a press release.¹ "This recognition specifically validates the promise of STAR0602 as a novel treatment option for patients with TMB-H metastatic colorectal cancer, which is insensitive to PD-1 treatment."

For safety, the most common treatment-related AEs observed were primarily transient grade 1 and 2 cytokine release syndrome.² These were seen after the first and second infusions. There were also no grade 4 AEs or immune effector cell–associated neurotoxicity syndrome reported.

The recommended phase 2 dose of 0.08 mg/kg was selected for further evaluation in phase 2 dose expansion studies, based on safety data, pharmacokinetic and pharmacodynamic findings, and the preliminary antitumor activity.

Invikafusp alfa entered into phase 2 clinical trials at the end of 2024. Additional efficacy results from the study are expected to be presented later this year.

"Marengo's selective Vβ T cell activation approach targeting specific T-cell subsets enriched in Tumor-infiltrating lymphocytes to enhance anti-tumor activity is unique and highly promising," said Bruce Chabner, MD, clinical director emeritus for the Massachusetts General Hospital Cancer Center and professor of medicine at Harvard Medical School, in the press release.¹ "The phase 2 clinical investigation of invikafusp alfa is ongoing and this novel treatment could lead to a new class of therapeutics for tumor types that are PD-1 insensitive or resistant, especially in colorectal cancer where current treatment options remain limited."

REFERENCES:

1. Marengo's first-in-class invikafusp alfa (STAR0602) receives U.S. FDA fast track designation for treatment of unresectable, locally advanced, or metastatic colorectal cancers with high tumor mutational burden (TMB-H). News release. Marengo Therapeutics, Inc. January 8, 2025. Accessed January 8, 2025. https://tinyurl.com/zbcerb9k

2. Gulley JL. 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. Presented at: 2024 SITC Annual Meeting; November 6-10, 2024; Houston, TX. Abstract LBA-1470.