Clinical trial NCT04240704: Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-Hodgkins Lymphoma
Chronic Lymphocytic Leukemia
Keywords: CLL
NHL
CCR7
JBH492
ADC
Chronic Lymphocytic Leukemia
Non-Hodgkins Lymphoma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-01-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Incidence and severity of dose limiting toxicities (DLTs)
timeFrame: 32 months
measure: Incidence and severity of Adverse Events (AEs)
timeFrame: 32 months
measure: Incidence and severity of Serious Adverse Events (SAEs)
timeFrame: 32 months
measure: Number of patients with dose interruptions
timeFrame: 32 months
measure: Number of patients with dose reductions
timeFrame: 32 months
measure: Dose intensity
timeFrame: 32 months
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 32 months
measure: Best overall response (BOR)
timeFrame: 32 months
measure: Duration of Response (DOR)
timeFrame: 32 months
measure: Progression Free Survival (PFS)
timeFrame: 32 months
measure: Pharmacokinetics (PK) parameter AUClast
timeFrame: 32 months
measure: PK parameter AUCinf
timeFrame: 32 months
measure: PK parameter AUCtau
timeFrame: 32 months
measure: PK parameter Cmax and Cmin
timeFrame: 32 months
measure: PK parameter Tmax
timeFrame: 32 months
measure: PK parameter T1/2
timeFrame: 32 months
measure: Incidence of anti-JBH492 antibodies
timeFrame: 32 months
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
Study officials:
References: