Neoplasms
Conditions
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.
Interventions
DRUGJNJ-88549968
JNJ-88549968 will be administered.
DRUGRuxolitinib
For US sites: Ruxolitinib will be administered for participants with MF only.
DRUGMomelotinib
For US sites: Momelotinib will be administered for participants with MF only.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1, Part 1b (US Only): Number of Participants With Dose Limiting Toxicity (DLT) | Approximately up to 35 days after first dose of study treatment | 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. |
| Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) | Up to 2 years | 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. |
| Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants with Adverse Events (AEs) by Severity | Up to 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1, 2, Part 1b (US Only), Part 2b (US Only): Serum Concentration of JNJ-88549968 | Up to 2 years | Serum samples will be analyzed to determine concentrations of JNJ-88549968. |
| Part 1, 2, Part 1b (US Only), Part 2b (US Only): Number of Participants With Presence of Anti-Drug Antibodies to JNJ-88549968 | Up to 2 years | Number of participants with presence of anti-drug antibodies to JNJ-88549968 will be reported. |
| Part 1, 2, Part 1b (US Only), Part 2b (US Only): Overall Response Rate | Up to 2 years | 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. |
| Part 1, 2, Part 1b (US Only), Part 2b (US Only): Complete Response (CR) Rate | Up to 2 years | 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. |
| Part 1, 2, Part 1b (US Only), Part 2b (US Only): Time to Response (TTR) | Up to 2 years | 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. |
| Part 1, 2, Part 1b (US Only), Part 2b (US Only): Duration of Response (DOR) | Up to 2 years | 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. |
| Part 2, Part 2b (US Only): Change From Baseline in Myeloproliferative Neoplasm (MPN) Symptom Burden | Baseline up to 2 years | Change from baseline in MPN symptom burden assessed using patient reported outcome (PRO) questionnaire will be reported in this outcome measure. |
Countries
Canada, France, Germany, Israel, Italy, Spain, United Kingdom, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed