Invikafusp Alfa Receives Second FDA Fast Track Designation for TMB-High Solid Tumors

The FDA has granted a second fast track designation (FTD) to invikafusp alfa (STAR0602), an investigational immunotherapy, for the treatment of patients with unresectable, locally advanced or metastatic tumor mutational burden-high (TMB-H) solid tumors that have progressed following prior treatment, including immune checkpoint inhibition, and who have no satisfactory treatment options, according to Marengo Therapeutics, the agent’s developer.¹

The new designation expands invikafusp alfa’s existing FTD, granted in January 2025 for TMB-H colorectal cancer, to a tissue-agnostic indication encompassing solid tumors regardless of their site of origin.

Clinical Data Supporting Fast Track Designation

The designation is supported by findings from the ongoing phase 1/2 STARt-001 study (NCT05592626), which is evaluating invikafusp alfa monotherapy in patients with advanced solid tumors that are resistant or refractory to PD-1–directed therapy. The company reported objective responses across multiple tumor types, including colorectal, gastric, breast, urothelial, endometrial, gastroesophageal, head and neck, and lung cancers.²

Invikafusp alfa is a bispecific dual T-cell agonist designed to selectively activate a subset of T cells through T-cell receptor engagement and a costimulatory signal. The approach is intended to expand clonally diverse effector memory T cells and strengthen antitumor immune responses in patients whose cancers do not respond to, or progress after, immune checkpoint blockade.

“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,” Ke Liu, MD, PhD, chief development officer of Marengo Therapeutics, said in the company’s news release.

Regulatory and Development Context

Marengo is also evaluating invikafusp alfa in combination with standard-of-care therapies, including an antibody-drug conjugate, to assess its potential in earlier lines of treatment. The phase 2 expansion of STARt-001 is ongoing.¹

“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,” Eric Rubin, MD, a member of Marengo Therapeutics’ scientific advisory board and former senior vice president of global clinical oncology at Merck, said in the company’s news release.

Updated phase 2 findings from the ongoing STARt-001 study are scheduled for oral presentation at the European Society for Medical Oncology (ESMO) Congress 2026 on October 23. Invikafusp alfa remains investigational and has not been approved by the FDA or any other regulatory authority.¹

REFERENCES

1. Marengo Therapeutics receives second US 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. News release. Marengo Therapeutics. October 15, 2026. Accessed October 16, 2026. https://tinyurl.com/52fucbjs

2. A study of invikafusp alfa (STAR0602) in participants with advanced solid tumors (STARt-001). ClinicalTrials.gov. Updated August 11, 2026. Accessed October 16, 2026. https://clinicaltrials.gov/study/NCT05592626