FDA Grants Orphan Drug Designation to Bispecific Antibody LAVA-051 for CLL


The FDA has granted an orphan drug designation to LAVA-051, a CD1d-targeted Gammabody, for the treatment of patients with chronic lymphocytic leukemia.

Stephen Hurly

Stephen Hurly

The FDA has granted an orphan drug designation to LAVA-051, a CD1d-targeted Gammabody, for the treatment of patients with chronic lymphocytic leukemia (CLL), according to an announcement from LAVA Therapeutics N.V.1

The bispecific antibody was designed to recruit the immune system to attack cancer cells that express CD1d through the preferential activation of gamma delta T cells and type 1 natural killer T (NKT) cells. Proof of concept was established when the agent showcased safety and efficacy in several preclinical models.2 LAVA-051 can activate Vγ9Vδ2 T cells and invariant NKT cells in a target-dependent manner.

“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 Gammabody platform that is designed to unlock the full anticancer potential of this specialized effector cell population,” Stephen Hurly, president and chief executive officer of LAVA Therapeutics N.V., stated 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.”

The safety and efficacy of single-agent LAVA-051 is currently under exploration in patients with CD1d-positive CLL, multiple myeloma, and acute myeloid leukemia (AML) as part of an ongoing 2-part phase 1/2 trial (NCT04887259).3

To be eligible for enrollment to both parts of the trial, patients must be at least 18 years of age, have confirmed tumor cell CD1d expression, and have a documented diagnosis of CLL, multiple myeloma, or AML and have been unresponsive to or have relapsed following previous therapy; patients were either not amenable to standard approaches or do not have standard options available to them.

Moreover, patients needed to have a predicted life expectancy of at least 3 months, an ECOG performance status of 0 or 1, and acceptable renal, hepatic, and hematological function.

If patients previously underwent an allogeneic bone marrow transplant and they had active acute or chronic graft-versus-host disease requiring more than 10 mg of prednisone or an equivalent corticosteroid, they were excluded. Patients could not have previously received radiotherapy, immunotherapy, or chemotherapy within 2 weeks before treatment, nor could they have received biological therapy with an investigational product within 4 weeks prior to treatment.

Other exclusion criteria comprised having concomitant malignancies apart from carcinoma in situ, basal, or squamous cell carcinoma; an uncontrolled or severe intercurrent medical condition; known uncontrolled central nervous system involvement; unstable cardiovascular function; or a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease.

In part 1 of the trial, the dose-escalation portion, the bispecific antibody will be given via intravenous infusion and escalated until an estimated therapeutic dose level has been reached. In the dose-expansion portion of the research, participants will be given LAVA-051 at the recommended phase 2 dose established in part 1 in disease-specific cohorts for multiple myeloma and/or CLL and/or AML.

The primary outcome measures for part 1 of the trial are frequency of dose-limiting toxicities within the first 28 days of treatment and the frequency of adverse effects (AEs). For part 2, investigators will focus on the frequency and severity of AEs through study completion and the number of patients who experience an antitumor response.

A secondary outcome measure for part 1 is the number of patients who respond to treatment. For both parts of the research, investigators will also examine the pharmacokinetics of LAVA-051, biomarkers in the form of the agent binding to Vγ9Vδ2 T cells and CD1d-positive cells, and the incidence of patients who develop antidrug antibodies to LAVA-051.

Findings from the dose-escalation phase of the research are anticipated in the first half of 2022. Top-line clinical data from the phase 2a expansion cohorts are expected in the second half of 2022.


  1. Lava Therapeutics receives FDA orphan drug designation for LAVA-051 for the treatment of chronic lymphocytic leukemia. News release. October 15, 2021. Accessed October 18, 2021. https://bit.ly/3jds82c
  2. Pipeline. Lava Therapeutics N.V. Accessed October 18, 2021. https://bit.ly/3vmbJx4
  3. Trial with LAVA-051 in patients with relapsed/refractory CD1d (cluster of differentiation (CD)1d)-positive CLL, MM, AML. ClinicalTrials.gov. Updated June 16, 2021. Accessed October 18, 2021. https://clinicaltrials.gov/ct2/show/NCT04887259
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