LAVA Therapeutics has announced the discontinuation of LAVA-1207 development for metastatic castration-resistant prostate cancer (mCRPC), despite the phase 1/2a trial showing some encouraging signals.
The trial (NCT05369000), designed to evaluate safety and preliminary efficacy, met the company’s standards for tolerability but failed to meet internal benchmarks necessary for continued development. Notably, this decision was not driven by safety concerns. Patients currently receiving the agent can continue treatment if deemed appropriate by their physicians.

During the trial’s phase 1 portion, several patients exhibited prostate-specific antigen (PSA) reductions. Data also suggested that higher baseline levels of circulating Vδ2 T cells correlated with longer treatment durations. The study explored multiple approaches, including dose escalation and combination strategies with pembrolizumab and low-dose interleukin 2 (IL-2).
The trial aimed to identify the optimal phase 2 dose while gathering pharmacokinetic, pharmacodynamic, and preliminary antitumor activity data.

LAVA-1207, a gamma-delta T-cell engager targeting PSMA-positive tumors, was developed to bind with Vδ2 T cells and PSMA with high affinity.
The agent’s mechanism proposed that adding an anti–PD-1 antibody, like pembrolizumab, could enhance its efficacy by overcoming inhibitory signals on T-cell activity. Although the trial provided valuable insights into patient selection and the agent’s biological effects, the data ultimately fell short of advancing to the next phase.

Following this decision, LAVA Therapeutics has shifted its focus to its pipeline’s lead program, LAVA-1266, which targets acute myeloid leukemia and myelodysplastic syndrome. The company will also continue collaborating with industry partners and investing in preclinical programs. With approximately $79 million in cash reserves, LAVA Therapeutics remains financially positioned to pursue its updated priorities into 2027.

While the end of LAVA-1207’s development in mCRPC marks a setback, the trial’s findings contribute to the broader understanding of gamma-delta T-cell engagers, potentially informing future approaches in immuno-oncology.

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