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Trial With LAVA-051 in Patients With Relapsed/Refractory CD1d (Cluster of Differentiation (CD)1d)-Positive CLL, MM, AML

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ClinicalTrials.gov Identifier: NCT04887259
Recruitment Status : Recruiting
First Posted : May 14, 2021
Last Update Posted : May 24, 2021
Sponsor:
Information provided by (Responsible Party):
Lava Therapeutics

Brief Summary:

An open-label, Phase 1/2a study to evaluate the safety and tolerability of LAVA-051 as monotherapy in patients with relapsed or refractory CD1d-positive Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) or Acute Myeloid Leukemia (AML).

Condition or disease: Chronic Lymphocytic Leukemia (CLL); Multiple Myeloma (MM); Acute Myeloid Leukemia (AML)

Intervention/ treatment; Biological - LAVA-051

Phase 1/2a


Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Multiple Myeloma Acute Myeloid Leukemia Biological: LAVA-051 Phase 1 Phase 2

Detailed Description:
This is a phase 1/2a, first-in-human study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary anti-tumor activity of LAVA-051; a humanized gamma-delta bispecific T-cell engager (bsTCE) antibody, as monotherapy in subjects with relapsed or refractory CD1d-positive CLL, MM, or AML.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: phase 1 sequential dose escalation cohorts phase 2 parallel disease specific cohorts
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 and 2a Open-label Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of LAVA-051 in Patients With Relapsed or Refractory CD1d-positive CLL, MM, or AML
Estimated Study Start Date : May 18, 2021
Estimated Primary Completion Date : September 24, 2023
Estimated Study Completion Date : December 30, 2023


Arm Intervention/treatment
Experimental: Single arm

In part 1 (dose escalation) LAVA-051 will be administered via intravenous infusion with dose escalation until an estimated therapeutic dose level has been reached.

In part 2 (dose expansion) patients will receive LAVA-051 at the recommended phase 2 dose(s) established in part 1 of the study in disease specific cohorts for MM and/or CLL and/or AML

Biological: LAVA-051

In part 1 (dose escalation) LAVA-051 will be administered via intravenous infusion.

In part 2 (dose expansion) LAVA-051 will be administered at the recommended phase 2 dose(s) and interval(s)





Primary Outcome Measures :
  1. Part 1; Frequency of dose limiting toxicity (DLT) [ Time Frame: first 28 days of treatment ]
    A DLT is defined as an adverse event that is unrelated to disease progression, intercurrent illness, or concomitant medications and is occurring during the first 28 days of treatment. These events will be classified according to the CTCAE v5.0; CRS will be evaluated according to the ASTCT consensus criteria

  2. Part 1; Safety; frequency and severity of Adverse Events using the CTCAE version 5.0 and ASTCT grading for CRS. [ Time Frame: Through study completion, 6 months ]
    Frequency and severity of Adverse Events using the Common Terminology Criteria and grading for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) grading for Cytokine Release Syndrome (CRS).

  3. Part 2; Safety; frequency and severity of Adverse Events using the CTCAE version 5.0 and ASTCT grading for CRS. [ Time Frame: Through study completion, 6 months ]
    Frequency and severity of Adverse Events using the Common Terminology Criteria and grading for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) grading for Cytokine Release Syndrome (CRS).

  4. Part 2; Number of patients who achieve an antitumor response [ Time Frame: Through study completion, 6 months ]
    Antitumor response will be assessed for CLL according most recent International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guideline, for MM to the most recent International Myeloma Working Group (IMWG) criteria, for AML to the most recent European LeukemiaNet (ELN) criteria


Secondary Outcome Measures :
  1. Part 1; Number of patients who achieve an antitumor response [ Time Frame: Through study completion, 6 months ]
    Antitumor response will be assessed for CLL according most recent International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guideline, for MM to the most recent International Myeloma Working Group (IMWG) criteria, for AML to the most recent European LeukemiaNet (ELN) criteria

  2. Part 1 & part 2; Pharmacokinetics of LAVA-051, area under the plasma concentration versus time curve (AUC) [ Time Frame: first 28 days of treatment ]
    Area under the plasma concentration versus time curve (AUC) of LAVA-051 will be assessed in the patients treated with LAVA-051

  3. Part 1 & part 2; Biomarkers, binding of LAVA-051 to Vγ9Vδ2-T cells (population of T cells that have a critical role in immune surveillance) [ Time Frame: Through study completion, 6 months ]
    Binding of LAVA-051 to Vγ9Vδ2-T cells will be measured in serum and on tumor samples

  4. Part 1 & part 2; Biomarkers, binding of LAVA-051 to CD1d positive tumor cells [ Time Frame: Through study completion, 6 months ]
    Binding of LAVA-051 to CD1d positive tumor cells will be measured in serum and on tumor samples

  5. Part 1 & part 2; Incidence of patients that develop anti-drug antibodies to LAVA-051 [ Time Frame: Through study completion, 6 months ]
    Potential development of antibodies (anti-drug antibodies) to LAVA-051 will be evaluated in plasma samples collected from all patients.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for both Part 1 and Part 2 of the trial:

  1. Patient must be 18 years of age inclusive or above, at the time of signing the informed consent.
  2. Confirmed tumor cell CD1d positivity/expression.
  3. Patients with documented diagnosis of CLL, MM, or AML who have failed to respond to or who have relapsed after prior therapy and are not amenable to standard treatments or for whom no standard treatments are available.
  4. Males or non-pregnant, non-breastfeeding females who are:

    1. Surgically sterile
    2. Female of childbearing potential with a negative pregnancy test prior to first dosing and compliant with a highly effective contraceptive regimen from signing of the informed consent form (ICF) through 90 days after the last Investigational Medicinal Product (IMP) administration.
    3. Female, postmenopausal defined as continuous amenorrhea for at least 12 consecutive months without an alternative medical cause and a serum follicle-stimulating hormone (FSH) measurement of > 40 IU/L).
    4. Male, compliant with an effective contraceptive regimen from signing of the ICF through 90 days after the last IMP administration.
    5. Male, refraining from donating sperm following from signing of the ICF through 90 days after the last IMP administration.
  5. Predicted life-expectancy of ≥ 3 months.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Adequate renal function ((estimated glomerular filtration rate (eGFR) per local laboratory> 40 mL/min/1.73m2)), hepatic function [(total bilirubin ≤ 2 times upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 times ULN] and hematological function (neutrophils ≥ 1 x109/L; platelet count ≥ 75x109/L
  8. Capable of giving signed and dated informed consent prior to initiation of any trial-related procedure that is not considered Standard of Care which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.

Exclusion Criteria:

  1. Prior allogeneic bone marrow transplant as long as the patient still has active acute or chronic graft versus host disease requiring >10 mg prednisone or equivalent corticosteroids.
  2. Concomitant malignancies except carcinoma in situ, basal or squamous cell skin carcinoma. Patients who had no evidence of disease from another primary cancer for 2 or more years are allowed to participate in the trial. Localized non-metastatic prostate cancer, not requiring systemic treatment, and for which no local treatment is planned, is allowed.
  3. Uncontrolled or severe intercurrent medical condition.
  4. Known uncontrolled central nervous system involvement.
  5. A significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this trial.
  6. Unstable cardiovascular function defined as: (a) symptomatic ischemia, or (b) uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block (left anterior fascicular block /right bundle branch block) will not be excluded), or (c) congestive heart failure New York Heart Association Class ≥ 3, or (d) myocardial infarction within 3 months.
  7. Previous treatment with radiotherapy, immunotherapy, or chemotherapy in the 2 weeks prior to initial IMP administration.
  8. Previous treatment with biological therapy or with an investigational product in the 4 weeks prior to initial IMP administration.
  9. Previous treatment of any systemic immunosuppressant within 2 weeks prior to initial IMP administration, with the exception of systemic corticosteroid use up to oral dose of 10 mg prednisolone daily (or equivalent for other steroids).
  10. Previous treatment with live or live attenuated vaccines within 2 weeks prior to initial IMP administration. Other (new) types of vaccines need to be evaluated as to their mode of action.
  11. Known non-CLL/MM/AML related pre-existing clinically relevant immunodeficiency disorders.
  12. Positive serological testing for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen [HBsAg] and hepatitis B core antibody (anti-HBc) negative, and hepatitis C virus antibody. Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative Polymerase Chain Reaction (PCR) within 6 weeks prior to initial IMP administration. Those who are PCR positive will be excluded.
  13. Known allergies, hypersensitivity, or intolerance to the excipients of the IMP.
  14. Major surgery within 4 weeks of initial IMP administration or planned surgery during the time the patient is expected to participate in the trial.
  15. Known ongoing drug and alcohol abuse in the opinion of the investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04887259


Contacts
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Contact: Peter Holleman +31 (0) 630 003 035 p.holleman@lavatherapeutics.com
Contact: Benjamin Winograd, MD, PhD +31 (0) 630 003 035 b.winograd@lavatherapeutics.com

Locations
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Netherlands
Amsterdam UMC, location AMC Recruiting
Amsterdam, Noord Holland, Netherlands, 1105 AZ
Contact: Arnon Kater, MD, PhD       a.p.kater@amsterdamumc.nl   
Amsterdam UMC, location VUmc Recruiting
Amsterdam, Noord-Holland, Netherlands, 1081 HV
Contact: Niels vd Donk, MD, PhD       n.vandedonk@amsterdamumc.nl   
Sponsors and Collaborators
Lava Therapeutics
Investigators
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Study Chair: Benjamin Winograd, MD, PhD Lava Therapeutics
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Responsible Party: Lava Therapeutics
ClinicalTrials.gov Identifier: NCT04887259    
Other Study ID Numbers: LV-002-S042
First Posted: May 14, 2021    Key Record Dates
Last Update Posted: May 24, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lava Therapeutics:
open-label
phase 1 dose escalation
phase 1 safety
phase 2 proof of concept
phase 2 safety
Additional relevant MeSH terms:
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Leukemia
Multiple Myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Lymphatic Diseases
Leukemia, B-Cell