The first patient has been dosed in the phase 1/2a clinical trial, designed to evaluate LAVA-051- a gamma-delta bispecific gamma-delta T cell engager that activates Vγ9Vδ2 T cells and type 1 natural killer T cells-in those with chronic lymphocytic leukemia, multiple myeloma, and acute myeloid leukemia.
The first patient has been dosed in the phase 1/2a clinical trial (NCT04887259), designed to evaluate LAVA-051- a gamma-delta bispecific gamma-delta T cell engager that activates Vγ9Vδ2 T cells and type 1 natural killer T (NKT) cells-in those with chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and acute myeloid leukemia (AML), according to a press release by LAVA Therapeutics.
“The dosing of the first patient with LAVA-051 is an important step towards harnessing the therapeutic potential of the Vγ9Vδ2 subset of gamma-delta T cells in the clinic,” said Benjamin Winograd, MD, PhD, chief medical officer of LAVA, in the press release. “Our preclinical data demonstrate that LAVA-051 targets CD1d-expressing tumors by activating both Vγ9Vδ2 T cells and type 1 NKT cells, leading to robust antitumor activity. These data make us confident that our dual-targeting approach may lead to important new treatment options for CD1d expressing hematological malignancies like CLL, MM and AML, which are devastating, difficult to treat cancers, for which novel treatments are needed.”
The phase 1/2a trial has an estimated enrollment of 55 participants with completion in December 2023. The study utilizes a sequential assignment, open-label design. The primary end points of phase 1 of the study are frequency of dose-limiting toxicities, and the safety, frequency, and severity of adverse events (AEs). Primary end points of phase 2 of the trial are safety and frequency of AEs, and the number of patients who achieve an anti-tumor response. Secondary end points for both phases include the number of patients who achieve an antitumor response, the pharmacokinetics of LAVA-051, biomarkers, and the incidents of patients who develop anti-drug antibodies to the agent.
During phase 1 of the single-arm study, patients will be administered the agent intravenously following a dose escalation scheme until a recommended phase 2 dose is reached. During phase 2, patients will be separated into disease-specific cohorts and will receive the recommended dose.
To be eligible for participation, patients must be 18 years of age or older; have confirmed CD1d-positive tumors; have a documented diagnosis of CLL, MM, or AML with progression and have failed to respond or relapsed after prior therapy and are not amendable to standard treatment; have a life expectancy of ≥3 months; have an ECOG status of 0 or 1; and have adequate renal function. Patients with prior allogeneic bone marrow transplant, concomitant malignancies, known uncontrolled central nervous system involvement, unstable cardiovascular function, or patients who are HIV positive are not eligible to participate.
“This important milestone marks LAVA’s transition to a clinical stage company. LAVA-051, the most advanced product candidate from our off-the-shelf antibody platform, is designed to utilize bi-specifics to unlock the full anti-cancer potential of a patient’s own gamma-delta T cells. We believe our approach overcomes the limitations of first-generation T cell engagers, reducing the risk of off-target toxicity, regulatory T-cell activation and cytokine release syndrome, while also amplifying efficacy through innate and adaptive immune responses. Adding to our momentum in the clinic, our second clinical program, LAVA-1207 in metastatic prostate cancer, is expected to enter the clinic before year end. We look forward to generating important clinical data to support our approach in both hematological malignancies and solid tumors,” said Stephen Hurly, president and chief executive officer of LAVA, in the press release.
LAVA-051 has two VHH domain antibodies that are linked using a short 5 amino acid glycine-serine linker: CD1d, which is also expressed in solid tumors such as prostate, cervical, breast, renal cell, and colorectal cancers, and the Vd2 chain of the Vγ9Vδ2 T cell receptor.
The study is currently recruiting in the Netherlands.