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

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)

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

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia; Non-Hodgkins Lymphoma
• Intervention / Treatment: Drug: JBH492

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, FIN-00029
    • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Freiburg im Breisgau, Germany, 79106
    • Novartis Investigative Site
• Israel
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Japan
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104 0045
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 03080
    • Novartis Investigative Site
• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Link to study results
• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Actual): September 5, 2024
• Study Completion (Actual): September 5, 2024

Study Registration Dates

• First Submitted: January 23, 2020
• First Submitted That Met QC Criteria: January 23, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Estimated): October 10, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: NHL; CLL; Chronic Lymphocytic Leukemia; ADC; Non-Hodgkins Lymphoma; CCR7; JBH492
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: CJBH492A12101; 2019-002666-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No