LAVA-051 for CLL Granted Orphan Drug Designation by FDA

LAVA-051 for the treatment of CLL was granted an orphan drug designation by the FDA. Results of a phase 1 study of the agent are expected in the first half of 2022.

The FDA has granted an orphan drug designation to LAVA-051, an agent designed to activate both VyVδ2 T cells and type 1 NKT cells meant to kill CD1d expressing tumor cells, for the treatment of chronic lymphocytic leukemia (CLL), according to a press release.1

LAVA-051 uses the Gammabody platform, a fully molecular, off-the-shelf, system allowing for the use of existing antibodies. This allows for the high potency of EC50 in low picomolar range and the potential expansion of activated Vγ9Vδ2 T cells.2

LAVA-051 is currently being evaluated in an ongoing phase 1/2 trial (NCT04887259). The sequential assignment trial has an estimated enrollment of 55 participants and an estimated study completion date of December 2023. The primary end points of phase 1 are the frequency of dose limiting toxicities and the safety, frequency, and severity of adverse events (AEs). The primary end points of phase 2 are the safety, frequency, and severity of AEs using the CTCAE version 5.0, and the number of patients who achieve an antitumor response. Secondary end points include the number of patients who achieved an antitumor response, the pharmacokinetics of LAVA-051, biomarkers, and the incidence of patients developing anti-drug antibodies to LAVA-051.3

During phase 1 of the study, LAVA-051 will be administered intravenously with dose escalation until an estimated therapeutic dose level has been reached. During the phase 2 dose-expansion portion, patients will receive LAVA-051 at the recommended dosing level in specific cohorts for CLL, acute myeloid leukemia, and multiple myeloma.

In order to participate, patients must be 18 years of age or older, confirmed CD1d positivity/expression, must have failed to respond or relapse after prior therapy, have a life expectancy of 3 months or greater, an ECOG score of 0 or 1, and have adequate renal, hepatic, and hematologic function. Patients with prior allogenic bone marrow transplant, uncontrolled central nervous system involvement, a significant history of any disease that in the option of the investigator would adversely affect their trial participation, unstable cardiovascular function, or previous radiation, immunotherapy, or chemotherapy within 2 weeks prior to initial dosing are not eligible to participate.

"We are excited to receive our first orphan drug designation from the FDA for LAVA-051, our most advanced product candidate from our off-the-shelf GammabodyTM platform that is designed to unlock the full anti-cancer potential of this specialized effector cell population,” said Stephen Hurly, president and chief executive officer, LAVA Therapeutics in a press release. “This designation will be helpful in enhancing our communication with the FDA on our development of LAVA-051. We are grateful to the FDA for highlighting the need for new and improved therapies to address the unmet needs in CLL.”

Results from the phase 1 dose escalation portion are expected in the first half of 2022.

1.Lava Therapeutics receives FDA orphan drug designation for LAVA-051 for the treatment of chronic lymphocytic leukemia. Lava Therapeutics. News release. October 15, 2021. Accessed October 15, 2021.
2.Gammabody™ Platform. Lava Therapeutics. Accessed October 15, 2021.
3.Trial with LAVA-051 in patients with relapsed/refractory CD1d (Cluster of Differentiation (CD)1d)-Positive CLL, MM, AML. Accessed October 15, 2021.