Chronic Lymphocytic Leukemia, Non-Hodgkins Lymphoma
Conditions
Keywords
CLL, NHL, CCR7, JBH492, ADC, Chronic Lymphocytic Leukemia, Non-Hodgkins Lymphoma
Brief summary
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.
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.
Interventions
DRUGJBH492
Anti-CCR7 antibody-drug conjugate (ADC)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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 |
| 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 |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
| 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). |
| 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) |
| Incidence of anti-JBH492 antibodies | 32 months | Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies) |
| 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) |
| 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. |
| 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. |
| 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 |
| 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) |
| 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) |
Countries
Finland, Germany, Israel, Japan, Singapore, South Korea, Spain
Outcome results
None listed