Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL)

• ClinicalTrials.gov Identifier: NCT04240704
• Recruitment Status: Recruiting
• First Posted: January 27, 2020
• Last Update Posted: December 6, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: January 23, 2020
• First Posted Date: January 27, 2020
• Last Update Posted Date: December 6, 2021
• Actual Study Start Date: September 7, 2020
• Estimated Primary Completion Date: June 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 23, 2020)

• 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.
• 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.
• 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.
• 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
• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 23, 2020)

• 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).
• 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.
• 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.
• 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
• 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)
• 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)
• 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)
• 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)
• 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)
• 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)
• Incidence of anti-JBH492 antibodies [ Time Frame: 32 months ]
  Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL)
• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Hodgkins Lymphoma
• Chronic Lymphocytic Leukemia

Intervention

Drug: JBH492

Anti-CCR7 antibody-drug conjugate (ADC)

Study Arms

Experimental: JBH492 single agent

Intervention: Drug: JBH492

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 23, 2020): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 15, 2023
• Estimated Primary Completion Date: June 15, 2023 (Final data collection date for primary outcome measure)

Eligibility 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 > 4 weeks before enrollment. 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.
• Impaired cardiac function or clinically significant cardiac disease
• Known history of Human Immunodeficiency Virus (HIV) infection
• Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection

Other inclusion and exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

Contact: Novartis Pharmaceuticals; +41613241111

• Listed Location Countries: Finland, Germany, Israel, Japan, Korea, Republic of, Singapore, Spain, United States

Administrative Information

• NCT Number: NCT04240704
• Other Study ID Numbers: CJBH492A12101
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: December 2021