Development of LAVA-1207 Discontinues in mCRPC

The development of LAVA-1207 as a potential treatment option for patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) has been discontinued, according to an announcement from LAVA Therapeutics.1

The decision to discontinue the development of the novel bispecific gamma-delta T-cell engager was made after data from a phase 1/2a trial (NCT05369000) did not reach LAVA’s internal benchmarks.1,2 The discontinuation was not related to safety concerns, and the agent will remain available for patients ongoing treatment at physician discretion.1

Findings from the phase 1 portion of the study showed that prostate-specific antigen (PSA) reductions occurred in several patients, and a higher baseline circulating Vd2 T-cell level was associated with a longer time on study. Safety and tolerability data were consistent with the intended mechanism of action of LAVA-1207.

“LAVA’s goal is to develop immuno-oncology medicines to improve the lives of [patients with] cancer. While we are disappointed that LAVA-1207 did not reach our predetermined success criteria, we are reprioritizing our pipeline to focus on LAVA-1266 for acute myeloid leukemia and myelodysplastic syndrome and will continue to support our partnered programs,” Stephen Hurly, president and chief executive officer of LAVA Therapeutics, stated in a news release. “We are pleased by the progress of our partnered programs, including a preclinical data presentation by Johnson & Johnson at [the 2024 ASH Annual Meeting] and ongoing enrollment in the phase 1 program by Pfizer. LAVA is well capitalized, with approximately $79 million in cash, and with this pipeline reprioritization, we expect our cash balance to fund the company into 2027.”

LAVA-1207 was designed to bind with high affinity to the Vδ2 chain of Vγ9Vδ2 T cells and PSMA.2 It was also hypothesized that an anti–PD-1 antibody, such as pembrolizumab (Keytruda), could potentiate the effect of LAVA12-07 since PD-1 could dampen Vγ9Vδ2 T-cell activity.

The phase 1/2a trial included a 3+3 dose-escalation portion in phase 1, along with expansion cohorts in phase 2a. The study enrolled patients with mCRPC whose disease had progressed following prior treatment with at least 1 androgen receptor pathway inhibitor and taxane-based chemotherapy; notably, patients who were deemed unsuitable to receive a taxane-based chemotherapy were permitted to enroll.

Progressive disease was defined by PSA level, RECIST 1.1 criteria, or the appearance of 2 or more bone metastases. All patients were required to have an ECOG performance status of 0 or 1, and a PSMA PET scan was performed at baseline.

The design of phase 1 included the evaluation of LAVA-1207 at 10 escalating dose levels. For cleared doses (levels 6, 7, and 8), low-dose subcutaneous interleukin 2 (IL-2) was added. Another dose-escalation arm was evaluating LAVA-1207 in combination with pembrolizumab at 400 mg once every 6 weeks.

The study’s primary end points were to assess the safety of LAVA-1207 alone or in combination with pembrolizumab or low-dose IL-2; and to determine the recommended phase 2 dose. Secondary end points included pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity. The effect of LAVA-1207 on circulating tumor cells and circulating tumor DNA served as exploratory end points.

The study began enrollment in February 2022, and as of April 10, 2024, 71 patients had been enrolled. Enrollment in dose-escalation cohorts 9 and 7A1 had been completed; enrollment in cohort 10 started in April 2024.

“We thank the patients, investigators, and our employees for supporting the LAVA-1207 clinical study,” Charlie Morris, MD, chief medical officer of LAVA Therapeutics, added in the news release.1 “The longer time to progression, with several patients on trial beyond 6 months and duration of treatment observed for patients with higher circulating gamma delta2 T cells, are consistent with the mechanism of action and support continued clinical investigation of the platform.”

References

1. LAVA reports third quarter 2024 financial results and announces pipeline reprioritization and cash runway extension into 2027. News release. LAVA Therapeutics. December 10, 2024. Accessed January 20, 2025. https://ir.lavatherapeutics.com/news-releases/news-release-details/lava-reports-third-quarter-2024-financial-results-and-announces
2. Mehra N, Voortman J, Wise DR, et al. Phase I/II trial of LAVA-1207, a novel bispecific gamma-delta T-cell engager alone, or with low dose IL-2 or pembrolizumab, in metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol. 2024;42(suppl 16):TPS2672. doi:10.1200/JCO.2024.42.16_suppl.TPS2672