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).

A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms

Myeloproliferative Disorders

Myeloproliferative Neoplasms

Blood Cancer

Hematologic Neoplasms

Hematologic Malignancies

Hematology

Hematological Malignancies

Essential Thrombocythemia

Myelofibrosis

Neoplasms

Cancer

JNJ-88549968

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

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.

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.

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.

Serum samples will be analyzed to determine concentrations of JNJ-88549968.

Number of participants with presence of anti-drug antibodies to JNJ-88549968 will be
reported.

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.

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.

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.

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.

Change from baseline in MPN symptom burden assessed using patient reported outcome (PRO)
questionnaire will be reported in this outcome measure.

In dose escalation (Part 1), participants will receive JNJ-88549968. The dose will be
escalated sequentially to determine the recommended phase 2 dose (RP2D) and optimal
dosing schedule(s) based on safety, pharmacokinetic, pharmacodynamic, and preliminary
assessment of efficacy across several dose regimens. In dose expansion (Part 2),
participants will receive JNJ-88549968 at the RP2D regimen(s) determined in dose
escalation (Part 1).

City of Hope

Moffit Cancer center

A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms

Trials at a glance

Trials at a glance

A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms

Outcome measures

Primary outcome measures

Secondary outcome measures