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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04240704
Collaborator
(none)
120
11
1
33.2
10.9
0.3

Study Details

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
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
Anticipated 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 :
Sep 7, 2020
Anticipated Primary Completion Date :
Jun 15, 2023
Anticipated Study Completion Date :
Jun 15, 2023

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) [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) [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) [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 [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 [32 months]

    Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions

  6. Dose intensity [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) [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) [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) [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) [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 [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 [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 [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 [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 [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 [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 [32 months]

    Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 Mayo Clinic Arizona Phoenix Arizona United States 85054
2 Mayo Clinic Rochester Rochester Minnesota United States 55905
3 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
4 Novartis Investigative Site Helsinki Finland FIN-00029
5 Novartis Investigative Site Dresden Germany 01307
6 Novartis Investigative Site Freiburg Germany 79106
7 Novartis Investigative Site Tel Aviv Israel 6423906
8 Novartis Investigative Site Chuo ku Tokyo Japan 104 0045
9 Novartis Investigative Site Seoul Korea, Republic of 03080
10 Novartis Investigative Site Singapore Singapore 169608
11 Novartis Investigative Site Barcelona Catalunya Spain 08035

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT04240704
Other Study ID Numbers:
  • CJBH492A12101
First Posted:
Jan 27, 2020
Last Update Posted:
Jun 3, 2022
Last Verified:
May 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 3, 2022