Description:
The purpose of the First-In-Human study is to assess safety, tolerability, pharmacokinetics
(PK), immunogenicity and preliminary efficacy of JBH492 as single agent.
Title
- 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)
Clinical Trial IDs
- ORG STUDY ID:
CJBH492A12101
- NCT ID:
NCT04240704
Conditions
- Non-Hodgkins Lymphoma
- Chronic Lymphocytic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
JBH492 | | JBH492 single agent |
Purpose
The purpose of the First-In-Human study is to assess safety, tolerability, pharmacokinetics
(PK), immunogenicity and preliminary efficacy of JBH492 as single agent.
Trial Arms
Name | Type | Description | Interventions |
---|
JBH492 single agent | Experimental | | |
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 12 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence and severity of dose limiting toxicities (DLTs) |
Time Frame: | 32 months |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Overall response rate (ORR) |
Time Frame: | 32 months |
Safety Issue: | |
Description: | 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). |
Measure: | Best overall response (BOR) |
Time Frame: | 32 months |
Safety Issue: | |
Description: | The best overall response (BOR) is the best reponse recorded in a patient from the start of treatment until disease progression. |
Measure: | Duration of Response (DOR) |
Time Frame: | 32 months |
Safety Issue: | |
Description: | 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. |
Measure: | Progression Free Survival (PFS) |
Time Frame: | 32 months |
Safety Issue: | |
Description: | 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 |
Measure: | Pharmacokinetics (PK) parameter AUClast |
Time Frame: | 32 months |
Safety Issue: | |
Description: | 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) |
Measure: | PK parameter AUCinf |
Time Frame: | 32 months |
Safety Issue: | |
Description: | The AUC from time zero to infinity (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4) |
Measure: | PK parameter AUCtau |
Time Frame: | 32 months |
Safety Issue: | |
Description: | 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) |
Measure: | PK parameter Cmax and Cmin |
Time Frame: | 32 months |
Safety Issue: | |
Description: | The maximum (peak) and minimum observed serum drug concentration (mass × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4) |
Measure: | PK parameter Tmax |
Time Frame: | 32 months |
Safety Issue: | |
Description: | The time to reach maximum (peak) serum drug concentration (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4) |
Measure: | PK parameter T1/2 |
Time Frame: | 32 months |
Safety Issue: | |
Description: | 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) |
Measure: | Incidence of anti-JBH492 antibodies |
Time Frame: | 32 months |
Safety Issue: | |
Description: | Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies) |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- CLL
- NHL
- CCR7
- JBH492
- ADC
- Chronic Lymphocytic Leukemia
- Non-Hodgkins Lymphoma
Last Updated
July 27, 2021