Non-Hodgkins LymphomaPhase 1NCT04240704
Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With CLL and NHL
A Phase 1 study testing JBH492 in people with Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukemia, run by Novartis Pharmaceuticals at 8 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia
- What is being tested?
- JBH492
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 8 sitesin 7 countries
- Study dates
- 7 Sep 2020to 5 Sep 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
8 sites in 7 countries.
8 sites in 7 countries
Germany2 sites
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Freiburg im Breisgau, 79106
About this study
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)
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.
Read the 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.
- Being tested
- JBH492
- Keywords
- CLL, NHL, CCR7, JBH492, ADC, Chronic Lymphocytic Leukemia, Non-Hodgkins Lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JBH492Drug
Anti-CCR7 antibody-drug conjugate (ADC)
| Study group | Role | What they receive |
|---|---|---|
| JBH492 single agent | Experimental | Patients with R/R CLL or NHL Receives: Drug: JBH492 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of dose limiting toxicities (DLTs)
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.
Measured: 32 months
Incidence and severity of Adverse Events (AEs)
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.
Measured: 32 months
Incidence and severity of Serious Adverse Events (SAEs)
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.
Measured: 32 months
Number of patients with dose interruptions
Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
Measured: 32 months
Number of patients with dose reductions
Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions
Measured: 32 months
Dose intensity
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
Measured: 32 months
Secondary outcomes (11)
Overall response rate (ORR)
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).
Measured: 32 months
Best overall response (BOR)
The best overall response (BOR) is the best reponse recorded in a patient from the start of treatment until disease progression.
Measured: 32 months
Duration of Response (DOR)
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.
Measured: 32 months
Progression Free Survival (PFS)
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
Measured: 32 months
Pharmacokinetics (PK) parameter AUClast
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)
Measured: 32 months
PK parameter AUCinf
The AUC from time zero to infinity (mass × time × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Measured: 32 months
PK parameter AUCtau
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)
Measured: 32 months
PK parameter Cmax and Cmin
The maximum (peak) and minimum observed serum drug concentration (mass × volume-1) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Measured: 32 months
PK parameter Tmax
The time to reach maximum (peak) serum drug concentration (time) for four analytes (total antibody, total antibody-drug-conjugate, DM4, sDM4)
Measured: 32 months
PK parameter T1/2
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)
Measured: 32 months
Incidence of anti-JBH492 antibodies
Number of subjects with anti-JBH492 antibodies (Anti-Drug Antibodies)
Measured: 32 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2020
- Study start7 Sep 2020
- Primary completion5 Sep 2024
- Study completion5 Sep 2024
Why it stopped: Business, strategic, and development considerations and not due to any safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkins LymphomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04240704
- Sponsor's protocol ID
- CJBH492A12101
- Other IDs
- 2019-002666-12, 2019
- Status last verified
- Oct 2025
- First submitted
- 23 Jan 2020
- Last updated
- 10 Oct 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04240704
- Acronym / sponsor ID
- CJBH492A12101
- Keywords
- CLL, NHL, CCR7, JBH492, ADC, Chronic Lymphocytic Leukemia, Non-Hodgkins Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business, strategic, and development considerations and not due to any safety concerns
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Sep 2020 (actual)
- Primary completion
- 5 Sep 2024 (actual)
- Study completion
- 5 Sep 2024 (actual)
- First posted
- 27 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| JBH492 single agent | Experimental | Drug: JBH492Patients with R/R CLL or NHL |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Confirmed diagnosis of chronic lymphocytic leukemia (CLL)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JBH492Anti-CCR7 antibody-drug conjugate (ADC) | Drug | JBH492 single agent |
Primary outcome
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
11 secondary outcomes
Overall response rate (ORR)
Time frame: 32 months
Best overall response (BOR)
Time frame: 32 months
Duration of Response (DOR)
Time frame: 32 months
Progression Free Survival (PFS)
Time frame: 32 months
Pharmacokinetics (PK) parameter AUClast
Time frame: 32 months
PK parameter AUCinf
Time frame: 32 months
PK parameter AUCtau
Time frame: 32 months
PK parameter Cmax and Cmin
Time frame: 32 months
PK parameter Tmax
Time frame: 32 months
PK parameter T1/2
Time frame: 32 months
Incidence of anti-JBH492 antibodies
Time frame: 32 months
Results and safety
The study was stopped early (reason given: Business, strategic, and development considerations and not due to any safety concerns). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2025.
- Link to study resultsLink provided by the sponsor.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JBH492 in people with Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukemia, run by Novartis Pharmaceuticals at 8 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany, Finland, Israel, Japan, Singapore and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business, strategic, and development considerations and not due to any safety concerns). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of dose limiting toxicities (DLTs) (time frame: 32 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2025.