Trial of LAVA-051 in Patients With Relapsed/Refractory CLL, MM, or AML

Study Overview
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Brief Summary
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A phase 1/2a, first-in-human trial to evaluate the safety and tolerability of LAVA-051 in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM), or Acute Myeloid Leukemia (AML).

Detailed Description
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An open-label, phase 1/2a dose escalation trial with disease-specific expansion cohorts to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary anti-tumor activity of LAVA-051 in patients with relapsed or refractory CLL, MM, or AML.

Official Title
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A Phase 1/2a Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of LAVA-051 in Patients With Relapsed or Refractory CLL, MM, or AML

Conditions
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Chronic Lymphocytic Leukemia, Multiple Myeloma, Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: LAVA-051
* Biological: Interleukin 2


Participation Criteria
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Eligibility Criteria
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KEY INCLUSION CRITERIA Patient must be 18 years of age inclusive or above at the time of signing the informed consent. Patients with documented diagnosis of relapsed or refractory 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. Predicated life expectancy of ≥ 3 months. ECOG performance status of 0 or 1. Males or non-pregnant, non-breastfeeding females who are either: Surgically sterile. Female of childbearing potential with a negative pregnancy test and compliant with an effective contraceptive regimen. Female, postmenopausal. Male compliant with an effective contraceptive regimen. Male refraining from donating sperm. Capable of giving signed and dated informed consent prior to initiation of any trial-related procedures. KEY EXCLUSION CRITERIA Prior allogeneic bone marrow transplant if the patient still has active acute or chronic graft versus host disease requiring >10 mg prednisone or equivalent corticosteroids. 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. Uncontrolled or severe intercurrent medical condition. Previous treatment with an aminobisphonsphonate IV (e.g. ibandronate, pamidronate, zoledronate) within 4 weeks prior to initial IMP administration. Known ongoing drug or alcohol abuse in the opinion of the investigator. Previous autologous haematopoietic stem cell transplantation (HSCT) or treatment with Chimeric Antigen Receptor (CAR) T-cell therapy within 6 months prior to initial IMP administration. Immunodeficiency disorders. Patients with Richter's transformation are excluded. Other eligibility criteria will apply during full screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAVA-051<br>Part 1 (dose escalation): LAVA-051 will be given to patients via intravenous (IV) infusion with dose escalation. A selected group of patients will also receive a low dose of interleukin 2 via subcutaneous injection. Group A: LAVA-051 Group B: LAVA-051 + low dose interleukin 2 Part 2 (dose expansion): patients will receive LAVA-051 at the dose and regimen established in Part 1 of the study | Biological: LAVA-051<br>* In part 1 and part 2, LAVA-051 will be administered via intravenous (IV) infusion<br>Biological: Interleukin 2<br>* In Part 1 and Part 2, a low dose of interleukin 2 will be given via subcutaneous injection with LAVA-051 in a selected group of patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 & Part 2 - Frequency and severity of AEs: | Frequency, severity, and grading of Adverse Events using the Common Terminology Criteria and grading for Adverse Events (CTCAE) v5.0. CRS will be evaluated using the ASTCT. | Approximately 6 months | 
| Part 1 - Frequency and type of DLT | 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 | First 28 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 & Part 2: Number of participants with an antitumor response | Antitumor response for CLL per iwCLL guidelines, MM per IMWG-based response criteria, and AML per ELN criteria | Approximately 6 months | 
| Part 1 & Part 2: Pharmacokinetics of LAVA-051, area under the plasma concentration versus time curve (AUC) | Area under the plasma concentration versus time curve (AUC) of LAVA-051 will be assessed in all patients treated with LAVA-051 | Approximately 6 months | 
| Part 1 & Part 2: Incidence and prevalence anti-LAVA-051 antibodies | Development of antibodies (anti-drug antibodies) to LAVA-051 will be evaluated | Approximately 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, Phase 1 dose escalation, Phase 1 safety, Phase 2 safety, Open label, MM, AML, relapsed, refractory