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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04240704
• Other study ID #: CJBH492A12101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 7, 2020
• Est. completion date: September 17, 2024

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: September 17, 2024
• Est. primary completion date: September 17, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkins Lymphoma

Intervention

Drug:
• JBH492
Anti-CCR7 antibody-drug conjugate (ADC)

Locations

Country	Name	City	State
Finland	Novartis Investigative Site	HUS
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Freiburg
Israel	Novartis Investigative Site	Tel Aviv
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Korea, Republic of	Novartis Investigative Site	Seoul
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Finland,  Germany,  Israel,  Japan,  Korea, Republic of,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	PK parameter T1/2	The elimination half-life associated with the terminal slope (?z) of a semi logarithmic concentration-time curve (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)	32 months
Secondary	Incidence of anti-JBH492 antibodies	Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)	32 months