START-001 Study of STAR0602 Doses First Patient With PD-1 Refractory Solid Tumors

The START-001 trial will administer STAR0602 to patients with PD-1 refractory advanced solid tumors in order to evaluate the safety, tolerability, and preliminary clinical activity of the agent as a monotherapy.

About the Phase 1/2 START-001 Trial

Trial Name: A Phase 1/2, First-in-Human, Open-Label, Dose Escalation and Expansion Study of STAR0602, a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule, in Subjects With Unresectable, Locally Advanced, or Metastatic Solid Tumors That Are Antigen-rich (START-001) Identifier: NCT05592626

Sponsor: Marengo Therapeutics, Inc.

Recruitment Contact: Ke Liu, MD, PhD, +1 (617) 917-4980,

Completion Date: October 2026

The first patient has been dosed with STAR0602 in the ongoing phase 1/2 START-001 trial (NCT05592626) evaluating the agent in a biomarker-enriched cohort of patients with PD-1 refractory advanced solid tumors.1

“The Center for Cancer Research's Center for Immuno-Oncology at the NCI [National Institutes of Health National Cancer Institute] was recently established to explore fundamental questions of cancer immunotherapy through rigorous preclinical studies and translate these findings into clinical trials with the goal of developing novel therapies for a spectrum of cancers with high unmet medical needs. We look forward to studying this novel TCR [T-cell receptor] agonist that selectively activates a subset of αβ T cells in cancer patients at the NCI," said James Gulley, MD, PhD, co-director of the Center for Immuno-Oncology, deputy director of the Center for Cancer Research at the NCI, and acting clinical director, NCI, in the press release.

STAR0602 is the first T-cell activator made as part of the STAR platform which is currently being developed by Marengo Therapeutics, Inc. The agent works by selectively targeting a common subset of T cell present in all cancers and activates the TCR with a T-cell co-stimulator. This then allows for the expansion of clonally enriched effector memory Vβ T cells that boost tumor immune responses to target tumors.

Preclinical models have demonstrated the potent antitumor activity with STAR0602. These are attributed to a distinct mechanism of action from existing cancer immunotherapies.

START-001 is an open-label, multicenter, phase 1/2 trial where investigators are examining the safety, tolerability, and preliminary clinical activity of STAR0602 when used as monotherapy in patients with advanced solid tumors, including those that are PD-1 refractory. The trial will consist of 2 parts, including the phase 1 dose-escalation portion and phase 2 dose-expansion part.

STAR0602 will be administered via intravenous infusion in patients with advanced solid tumors in the dose-escalation part of the trial. This portion aims to assess the safety and tolerability profile of STAR0602, as well as to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of the agent. Then, the phase 2 dose-expansion study will examine STAR0602 at the RP2D. Patients with advanced, antigen-rich solid tumors will be administered treatment at the RP2D to further evaluate STAR0602.

In order to be enrolled in part 1 of the study, patients must have a histologically confirmed solid tumor(s)that is unresectable, locally advanced, or metastatic. Standard curative therapies must not exist or no longer be effective, symptomatic central nervous system metastases must have been treated, and patients must be asymptomatic for at least 14 days.

In the study, the clinical activity of STAR0602 will be assessed by objective tumor response rate (ORR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS). The primary end points are to assess patients with dose-limiting toxicities in phase 1, number of patients with adverse events in parts 1 and 2, and ORR in part 2. Secondary end points include ORR in part 1, DOR, PFS, OS, and pharmacokinetics.

Patients are currently being enrolled at the NCI and Mass General Hospital/Harvard Medical School. Additional cancer centers are planned to join during the dose expansion portion of the study. The study has an estimated enrollment of 365 patients and a study completion date of October 2026.

"Cancer immunotherapy has transformed standard of care across many tumor settings and has significantly improved overall survival for patients with cancer. Despite these innovative therapies, most patients progress following treatment creating an urgent need to develop the next wave of novel therapeutics," added Ryan Sullivan, MD, associate director, melanoma program at Massachusetts General Hospital Cancer Center, in the press release. "We are excited to test this novel biology via reinvigorating the T-cell compartment in tumors to promote an antitumor immune response distinct from the PD-1 mechanism."

1. Marengo Therapeutics announces first patient dosed in phase 1/2 clinical trial of its novel TCR Vβ directed antibody-fusion molecule STAR0602, in cancer patients refractory to anti-PD1 therapy. News release. Marengo Therapeutics, Inc. January 27, 2023. Accessed January 31, 2023.
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