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

• ClinicalTrials.gov Identifier: NCT04240704
• Recruitment Status: Recruiting
• First Posted: January 27, 2020
• Last Update Posted: November 14, 2022
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Non-Hodgkins Lymphoma; Chronic Lymphocytic Leukemia	Drug: JBH492	Phase 1

Detailed 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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: September 7, 2020
• Estimated Primary Completion Date: August 30, 2024
• Estimated Study Completion Date: August 31, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of dose limiting toxicities (DLTs) [ Time Frame: 32 months ]
   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.
2. Incidence and severity of Adverse Events (AEs) [ Time Frame: 32 months ]
   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.
3. Incidence and severity of Serious Adverse Events (SAEs) [ Time Frame: 32 months ]

   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.
4. Number of patients with dose interruptions [ Time Frame: 32 months ]
   Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
5. Number of patients with dose reductions [ Time Frame: 32 months ]
   Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions
6. Dose intensity [ Time Frame: 32 months ]
   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

Secondary Outcome Measures :

1. Overall response rate (ORR) [ Time Frame: 32 months ]
   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).
2. Best overall response (BOR) [ Time Frame: 32 months ]
   The best overall response (BOR) is the best reponse recorded in a patient from the start of treatment until disease progression.
3. Duration of Response (DOR) [ Time Frame: 32 months ]
   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.
4. Progression Free Survival (PFS) [ Time Frame: 32 months ]
   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
5. Pharmacokinetics (PK) parameter AUClast [ Time Frame: 32 months ]
   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)
6. PK parameter AUCinf [ Time Frame: 32 months ]
   The AUC from time zero to infinity (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
7. PK parameter AUCtau [ Time Frame: 32 months ]
   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)
8. PK parameter Cmax and Cmin [ Time Frame: 32 months ]
   The maximum (peak) and minimum observed serum drug concentration (mass × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
9. PK parameter Tmax [ Time Frame: 32 months ]
   The time to reach maximum (peak) serum drug concentration (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
10. PK parameter T1/2 [ Time Frame: 32 months ]
    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)
11. Incidence of anti-JBH492 antibodies [ Time Frame: 32 months ]
    Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

Locations

United States, Arizona

Mayo Clinic Arizona; Withdrawn

Phoenix, Arizona, United States, 85054

United States, Minnesota

Mayo Clinic Rochester; Withdrawn

Rochester, Minnesota, United States, 55905

United States, Wisconsin

Medical College of Wisconsin; Withdrawn

Milwaukee, Wisconsin, United States, 53226

Finland

Novartis Investigative Site; Recruiting

HUS, Finland, FIN-00029

Germany

Novartis Investigative Site; Recruiting

Dresden, Germany, 01307

Novartis Investigative Site; Recruiting

Freiburg, Germany, 79106

Israel

Novartis Investigative Site; Recruiting

Tel Aviv, Israel, 6423906

Japan

Novartis Investigative Site; Recruiting

Chuo ku, Tokyo, Japan, 104 0045

Korea, Republic of

Novartis Investigative Site; Recruiting

Seoul, Korea, Republic of, 03080

Singapore

Novartis Investigative Site; Recruiting

Singapore, Singapore, 169608

Spain

Novartis Investigative Site; Recruiting

Barcelona, Catalunya, Spain, 08035

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04240704
• Other Study ID Numbers: CJBH492A12101
• First Posted: January 27, 2020
• Last Update Posted: November 14, 2022
• Last Verified: November 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

CLL; NHL; CCR7; JBH492; ADC; Chronic Lymphocytic Leukemia; Non-Hodgkins Lymphoma

Additional relevant MeSH terms:

Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes