FDA Grants Marengo’s Invikafusp Alfa Second Fast Track Designation in TMB-H Solid Tumors

The FDA has granted a second Fast Track Designation to invikafusp alfa (STAR0602), Marengo Therapeutics’ investigational bispecific dual T-cell agonist, for the treatment of unresectable, locally advanced, or metastatic tumor mutational burden-high (TMB-H) solid tumors that have progressed following prior treatment including immune checkpoint inhibition, in patients with no satisfactory treatment options.¹ The new designation expands the drug’s Fast Track status from a single tumor type, TMB-H colorectal cancer, which received the first designation in January 2025, to TMB-H solid tumors regardless of tissue of origin.¹

Marengo said it believes invikafusp alfa is the first immuno-oncology T-cell agonist to receive Fast Track Designation in a biomarker-defined, tissue-agnostic indication.¹

What did the FDA grant?

Fast Track Designation is intended to facilitate development and expedite review of drugs that treat serious conditions and fill an unmet medical need. It provides more frequent communication with FDA and, for drugs that meet the relevant criteria, eligibility for rolling review, accelerated approval, and priority review.¹

According to Marengo, the expanded designation is supported by objective responses in the ongoing Phase 1/2 STARt-001 study across multiple tumor types, including colorectal, gastric, breast, urothelial, endometrial, gastroesophageal, head and neck, and lung cancers.¹ Initial data were presented at the Society for Immunotherapy of Cancer 2025 Annual Meeting. Updated phase 2 results in this population will be presented in an oral session at the European Society for Medical Oncology Congress 2026 in Madrid on Oct. 23.¹

How does invikafusp alfa work?

Invikafusp alfa is a bifunctional antibody fusion protein. It consists of an agonist antibody targeting the variable beta 6 (Vβ6) and beta 10 (Vβ10) regions of the T-cell receptor (TCR), fused to the cytokine interleukin-2 (IL-2).² Marengo describes the molecule as combining a non-clonal mode of TCR activation with a T-cell co-stimulatory signal, an approach designed to expand clonally diverse, effector memory Vβ T cells.¹

“Years ago, when we pursued the tumor-agnostic TMB-H approval for pembrolizumab, the premise was that a high mutational burden gives T cells more to recognize. Yet many patients with TMB-H tumors do not respond to PD-1 blockades, such as pembrolizumab, or progress after it and are left with few treatment options,” said Eric Rubin, MD, a member of Marengo’s scientific advisory board and former senior vice president of global clinical oncology at Merck, where he led the initial development of pembrolizumab. “Invikafusp alfa takes a fundamentally different approach: rather than releasing a checkpoint on exhausted T cells, it directly expands new T cells that can act on that antigen-rich landscape. That makes it a compelling candidate for patients whose tumors do not or no longer respond to PD-1-directed therapy, regardless of where the tumor arises.”¹

Why does TMB-H status matter?

TMB measures the number of somatic mutations in a tumor’s genome. Tumors with high TMB, defined as at least 10 mutations per megabase, occur across many cancer types.¹ FDA granted accelerated approval to pembrolizumab on June 16, 2020, for adult and pediatric patients with unresectable or metastatic TMB-H solid tumors that had progressed following prior treatment. It was the first time the agency approved a cancer treatment for an indication based on TMB.³

In a BioPharm International® video interview on cancer vaccines, Eric von Hofe, PhD, chief executive officer of CellxLife, addressed patients who do not benefit from checkpoint inhibitors. “In those 60 to 70% where they are not effective, the issue there is that cancer vaccines can be effective in generating a new immune response to attack the cancer,” he said.

What happens next?

STARt-001 (NCT05592626) is a global phase 1/2 trial evaluating invikafusp alfa monotherapy in patients with advanced, antigen-rich solid tumors that are refractory or resistant to PD-1-directed therapy. Its phase 2 portion uses biomarker-enriched cohorts, including TMB-H and microsatellite instability-high (MSI-H) tumors, and expansion is ongoing.¹

The company is also evaluating invikafusp alfa in combination with standard-of-care therapies, including an antibody-drug conjugate, to support its potential in earlier lines of therapy.¹

“Across multiple clinical data sets, invikafusp alfa has shown encouraging monotherapy activity in heavily pretreated patients across tumor types that were either insensitive to checkpoint inhibitors or progressed after PD-1–directed therapy,” said Ke Liu, MD, PhD, chief development officer of Marengo Therapeutics.¹

Invikafusp alfa is investigational and has not been approved by FDA or any other regulatory authority.¹

References

1. Marengo Therapeutics. Marengo Therapeutics Receives Second U.S. FDA Fast Track Designation for Invikafusp Alfa, Expanding to a Tissue-Agnostic Indication Across Tumor Mutational Burden-High Solid Tumors That Progress After Prior Therapy, Including Checkpoint Inhibition. Press release. Published October 15, 2026. Accessed October 15, 2026.
2. National Cancer Institute. Anti-TCR Vb6/Vb10/IL-2 antibody fusion protein STAR0602. NCI Drug Dictionary. Accessed October 2026.
3. Marcus L, Fashoyin-Aje LA, Donoghue M, et al. FDA Approval Summary: Pembrolizumab for the treatment of tumor mutational burden-high solid tumors. Clin Cancer Res. Published online June 3, 2021.