Summary
In the phase 1/2 START-001 trial, four of 27 participants at selected doses had confirmed partial responses to invikafusp alfa. The early results also supported 0.08 mg/kg as the recommended phase 2 dose.
A phase 1/2 trial of invikafusp alfa reported confirmed tumour responses in some people with solid cancers, most of whom had tumours resistant to immune checkpoint blockade. In the combined trial groups treated at two selected doses, 4 of 27 participants had a confirmed partial response, an overall response rate of 14.8%. The results are early clinical evidence from the ongoing START-001 trial, not a measure of how the drug compares with other treatments.
Contents
How the treatment works
Invikafusp alfa is a bispecific, dual T-cell agonist antibody designed to target T-cell subsets identified by the Vβ6 and Vβ10 regions of the T-cell receptor. T cells are immune cells that can recognise and respond to threats; the receptor’s variable regions help distinguish different T-cell populations. Invikafusp alfa was developed to selectively expand and stimulate the Vβ6/Vβ10 subsets.
The trial examined the drug as a monotherapy in participants with mostly immune checkpoint blockade-resistant, antigen-rich solid tumours. Checkpoint-blocking medicines target inhibitory signals that can restrain immune activity. A treatment that stimulates selected T-cell populations represents a different approach to engaging the immune system, although its clinical effects require testing in patients.
What START-001 found
As of 12 March 2025, phase 1 had completed dose escalation in 34 participants across doses from 0.01 to 0.16 mg/kg. The initial phase 2 group included 18 participants. The study did not reach a maximum tolerated dose. Two participants had reversible dose-limiting toxicities: one at 0.08 mg/kg and one at 0.16 mg/kg.
Cytokine release syndrome was the most common treatment-related adverse event, mainly at grades 1 and 2. The researchers reported no treatment-related deaths or non-laboratory grade 4 adverse events. The study’s combined phase 1 and initial phase 2 groups at the optimal biological doses—0.08 and 0.12 mg/kg—had an overall response rate of 14.8% (4 of 27). All four were confirmed partial responses. They included responses in immunologically cold tumours, such as microsatellite-stable colorectal cancer and PD-L1-negative non-small cell lung cancer. No objective responses were seen at doses below 0.08 mg/kg.
The researchers also observed dose-dependent expansion of Vβ6/Vβ10 T cells in blood and within tumours. These cells were predominantly memory-like, a state associated with the capacity to persist and respond again. Interferon-γ and soluble CD25, pharmacodynamic markers measured after treatment, showed a similar dose pattern. These findings, alongside safety and pharmacokinetic data, informed the selection of 0.08 mg/kg as the recommended phase 2 dose.
What the results mean
The findings provide an early signal that invikafusp alfa can expand its intended T-cell populations and produce tumour responses in some participants, including in cancers described as immunologically cold. The authors concluded that phase 1 met its primary objectives of assessing safety and tolerability and selecting a recommended phase 2 dose; initial phase 2 results added preliminary evidence of anti-tumour activity.
The response estimate comes from 27 participants across two selected doses, so it is a preliminary measure from an early-phase study. START-001 is ongoing, and further phase 2 evaluation is planned. Marengo Therapeutics sponsored the study and was responsible for its design, data collection and analysis, and the decision to publish.