Brief Summary
The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D\[s\]) and optimal dosing schedule(s) of JNJ-88549968 in part 1 (Dose Escalation); to characterize the safety of JNJ- 88549968 at RP2D(s) in part 2 (Cohort Expansion). For U.S. sites: the purpose of this study is to characterize the safety and to determine the RP2D(s) and optimal dosing schedule(s) of JNJ-88549968 in Part 1 and part 1b (Dose Escalation), and to characterize the safety of JNJ-88549968 at the RP2D(s) in Part 2 and part 2b (Cohort Expansion), when given as monotherapy in essential thrombocythemia (ET) or myelofibrosis (MF), and with ruxolitinib or momelotinib in MF only.
Brief Title
A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
844-434-4210
Central Contact Email
Participate-In-This-Study1@its.jnj.com
Completion Date
Completion Date Type
Estimated
Conditions
Neoplasms
Eligibility Criteria
Inclusion Criteria:
* Be greater than or equal to (\>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent
* Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)
* Participants with ET and MF with risk characteristics as described in the protocol
* Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (\<=) 2
* For US sites: Eligible for ruxolitinib therapy as per drug label for participants naive to a janus kinase (JAK) inhibitor
Exclusion Criteria:
* Known allergies, hypersensitivity, or intolerance to the excipients of the study treatment
* Concurrent or recently diagnosed or treated malignancies present at the time of participant screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix, and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of study treatment in the opinion of both the investigator and sponsor's medical monitor. Participants cured of another malignant disease with no sign of relapse greater than or equal to (\>=) 3 years after treatment ended are allowed to enter the study
* Prior solid organ transplantation
* Either of the following regarding hematopoietic stem cell transplantation:
1. Prior treatment with allogenic stem cell transplant less than or equal to (\<=) 6 months before the first dose of JNJ-88549968 or
2. Evidence of graft versus host disease (GVHD) that requires immunosuppressant therapy
* History of clinically significant cardiovascular disease within 6 months prior to the first dose of study treatment
* Be greater than or equal to (\>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent
* Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)
* Participants with ET and MF with risk characteristics as described in the protocol
* Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (\<=) 2
* For US sites: Eligible for ruxolitinib therapy as per drug label for participants naive to a janus kinase (JAK) inhibitor
Exclusion Criteria:
* Known allergies, hypersensitivity, or intolerance to the excipients of the study treatment
* Concurrent or recently diagnosed or treated malignancies present at the time of participant screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix, and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of study treatment in the opinion of both the investigator and sponsor's medical monitor. Participants cured of another malignant disease with no sign of relapse greater than or equal to (\>=) 3 years after treatment ended are allowed to enter the study
* Prior solid organ transplantation
* Either of the following regarding hematopoietic stem cell transplantation:
1. Prior treatment with allogenic stem cell transplant less than or equal to (\<=) 6 months before the first dose of JNJ-88549968 or
2. Evidence of graft versus host disease (GVHD) that requires immunosuppressant therapy
* History of clinically significant cardiovascular disease within 6 months prior to the first dose of study treatment
Inclusion Criteria
Inclusion Criteria:
* Be greater than or equal to (\>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent
* Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)
* Participants with ET and MF with risk characteristics as described in the protocol
* Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (\<=) 2
* For US sites: Eligible for ruxolitinib therapy as per drug label for participants naive to a janus kinase (JAK) inhibitor
* Be greater than or equal to (\>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever the greater) at the time of informed consent
* Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET) or myelofibrosis (MF)
* Participants with ET and MF with risk characteristics as described in the protocol
* Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of less than or equal to (\<=) 2
* For US sites: Eligible for ruxolitinib therapy as per drug label for participants naive to a janus kinase (JAK) inhibitor
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06150157
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
88549968MPN1001
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A First-in-Human Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-88549968, a T-cell Redirecting Bispecific Antibody for CALR-mutated Myeloproliferative Neoplasms
Primary Outcomes
Outcome Description
Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. For US only: A DLT is any adverse event attributed to study treatment that meets the criteria for severity and duration and that occurs during the evaluation periods unless it can be incontrovertibly attributed to disease or other extraneous cause such as an accident.
Outcome Measure
Part 1, Part 1b (US Only): Number of Participants With Dose Limiting Toxicity (DLT)
Outcome Time Frame
Approximately up to 35 days after first dose of study treatment
Outcome Description
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Outcome Measure
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs)
Outcome Time Frame
Up to 2 years
Outcome Description
An adverse event is any untoward medical occurrence in a clinical study participant that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from grade 1 (mild) to grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse event. Cytokine release syndrome (CRS) and associated neurologic toxicity events (immune effector cell-associated neurotoxicity syndrome events \[ICANS\]) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.
Outcome Measure
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) by Severity
Outcome Time Frame
Up to 2 years
Secondary Ids
Secondary Id
2023-505584-36-00
Secondary Outcomes
Outcome Description
Serum samples will be analyzed to determine concentrations of JNJ-88549968.
Outcome Time Frame
Up to 2 years
Outcome Measure
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration of JNJ-88549968
Outcome Description
Number of participants with presence of anti-drug antibodies to JNJ-88549968 will be reported.
Outcome Time Frame
Up to 2 years
Outcome Measure
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968
Outcome Description
ORR is defined as the percentage of participants who achieve partial response (PR) and complete response (CR) according to modified International Working Group-Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) criteria and modified European Leukemia Net (ELN) consensus report.
Outcome Time Frame
Up to 2 years
Outcome Measure
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Overall Response Rate
Outcome Description
CR rate is defined as the percentage of participants who achieve a best response of CR according to disease as defined in modified IWG-MRT criteria and modified ELN consensus report.
Outcome Time Frame
Up to 2 years
Outcome Measure
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Complete Response (CR) Rate
Outcome Description
TTR is defined for participants who achieved PR or CR as the time from the first dose of study treatment to first response of PR or CR according to modified IWG-MRT criteria and modified ELN consensus report.
Outcome Time Frame
Up to 2 years
Outcome Measure
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Time to Response (TTR)
Outcome Description
DOR is defined for participants who achieved PR or CR as the time between the date of initial documentation of PR or CR to the date of first documented evidence of disease progression, as defined in modified IWG-MRT criteria and modified ELN consensus report, or death, whichever comes first.
Outcome Time Frame
Up to 2 years
Outcome Measure
Part 1, 2, Part 1b (US Only), Part 2b (US Only): Duration of Response (DOR)
Outcome Description
Change from baseline in MPN symptom burden assessed using patient reported outcome (PRO) questionnaire will be reported in this outcome measure.
Outcome Time Frame
Baseline up to 2 years
Outcome Measure
Part 2, Part 2b (US Only): Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
Montefiore
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Cancer --- NEOPLASMS
MeSH Terms
NEOPLASMS
RUXOLITINIB
N-(CYANOMETHYL)-4-(2-((4-(4-MORPHOLINYL)PHENYL)AMINO)-4-PYRIMIDINYL)BENZAMIDE