Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL

Study Overview
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Brief Summary
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The purpose of the First-In-Human study is to assess safety, tolerability, pharmacokinetics (PK), immunogenicity and preliminary efficacy of JBH492 as single agent.

Detailed Description
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This is a FIH, open-label, phase I/Ib, multi-center study, which consists of a dose escalation part of JBH492 as a single agent, followed by an expansion part. The escalation part will be conducted in patients with relapsed/refractory chronic lymphocytic leukemia (r/r CLL) and Non-Hodgkin's Lymphoma (r/r NHL). Once the MTD/RD of single agent JBH492 is determined, the study will continue with an expansion part with single agent JBH492 in defined patient populations

Official Title
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A Phase I/Ib Open-label, Multi-center Dose Escalation Study of JBH492 in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL)

Conditions
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Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: JBH492


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For patients with CLL: • Confirmed diagnosis of chronic lymphocytic leukemia (CLL) For patients with NHL: Histologically confirmed diagnosis of B- or T-cell non-Hodgkins lymphoma (NHL). Must have a site of disease amenable to biopsy, and be suitable and willing to undergo study required biopsies at screening and during therapy. Exclusion Criteria, applicable to both CLL and NHL: History of anaphylactic or other severe hypersensitivity/infusion reactions to ADCs, monoclonal antibodies (mAbs) and/or their excipients such that the patient in unable to tolerate immunoglobulin/monoclonal antibody administration Any prior history of treatment with maytansine (DM1 or DM4)-based ADC Known intolerance to a maytansinoid Patients with any active or chronic corneal disorders Patients who have any other condition that precludes monitoring of the retina or fundus Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated and provided that local treatment was completed >4 weeks before first dose of study treatment. Patients that have been effectively treated for CNS disease and are stable under systemic therapy may be enrolled provided all other inclusion and exclusion criteria are met. Patients who received prophylactic intrathecal treatment are eligible, if treatment discontinued >5 half-lives prior to the first dose of study treatment Impaired cardiac function or clinically significant cardiac disease Known history of Human Immunodeficiency Virus (HIV) infection Active HBV or HCV infection. Patients whose disease is controlled under antiviral therapy should not be excluded. Patients who are anti-HBcAb positive should be HBsAg negative and HBV-DNA negative to be eligible Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 12 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JBH492 single agent<br>Patients with R/R CLL or NHL | Drug: JBH492<br>* Anti-CCR7 antibody-drug conjugate (ADC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of dose limiting toxicities (DLTs) | A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value that occurs during the first cycle of treatment with JBH492 and meets any of the protocol specified criteria, unless incontrovertibly related to underlying disease, intercurrent illness or concomitant medications. | 32 months | 
| Incidence and severity of Adverse Events (AEs) | An adverse event ( treatment emergent) is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. | 32 months | 
| Incidence and severity of Serious Adverse Events (SAEs) | A Serious adverse event (SAE) is defined as one of the following: Is fatal or life-threatening Results in persistent or significant disability/incapacity Constitutes a congenital anomaly/birth defect Is medically significant Requires inpatient hospitalization or prolongation of existing hospitalization. | 32 months | 
| Number of patients with dose interruptions | Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions | 32 months | 
| Number of patients with dose reductions | Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions | 32 months | 
| Dose intensity | Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intensity | 32 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | The overall response rate (ORR), defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR), as per local review and according to the iwCLL guideline (CLL) or Lugano Classification (NHL). | 32 months | 
| Best overall response (BOR) | The best overall response (BOR) is the best reponse recorded in a patient from the start of treatment until disease progression. | 32 months | 
| Duration of Response (DOR) | The time between the date of first documented response (CR or PR) and the date of first documented progression or death due to underlying cancer. | 32 months | 
| Progression Free Survival (PFS) | PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause | 32 months | 
| Pharmacokinetics (PK) parameter AUClast | The area under the plasma concentration-time curve (AUC) of JBH492 from time zero to the last measurable concentration sampling time (tlast) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4) | 32 months | 
| PK parameter AUCinf | The AUC from time zero to infinity (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4) | 32 months | 
| PK parameter AUCtau | The AUC calculated to the end of a dosing interval (tau) (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4) | 32 months | 
| PK parameter Cmax and Cmin | The maximum (peak) and minimum observed serum drug concentration (mass × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4) | 32 months | 
| PK parameter Tmax | The time to reach maximum (peak) serum drug concentration (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4) | 32 months | 
| PK parameter T1/2 | The elimination half-life associated with the terminal slope (λz) of a semi logarithmic concentration-time curve (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4) | 32 months | 
| Incidence of anti-JBH492 antibodies | Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies) | 32 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, NHL, CCR7, JBH492, ADC, Chronic Lymphocytic Leukemia, Non-Hodgkins Lymphoma