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.

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

Neoplasms

Cancer

Ruxolitinib

JNJ-88549968

Momelotinib

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. 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.

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. For myelofibrosis
(MF) participants only, the study will explore a Phase 1b cohort in which the janus
kinase (JAK) inhibitor ruxolitinib or momelotinib is started in combination with
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, Part 2b [US only]), participants will receive JNJ-88549968 at the
RP2D regimen(s) determined in dose escalation (Part 1, Part 1b [US only]).

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).

City of Hope

Moffit Cancer center

University of Michigan

Memorial Sloan Kettering Cancer Center

Levine Cancer Institute

University of Pennsylvania

Sarah Cannon Cancer Institute

MD Anderson Cancer Center

Princess Margaret Cancer Centre University Health Network

Hopital Saint Louis

CH LYON SUD - Hematology

Universitaetsklinikum der RWTH Aachen

Charite Campus Benjamin Franklin

Medizinische Hochschule Hannover

Universitaetsklinikum Regensburg

Carmel Medical Center

Hadassah University Hospita Ein Kerem

Sheba Medical Center

Tel Aviv Sourasky Medical Center

Hosp. Univ. Germans Trias I Pujol

Hosp. Clinico Univ. de Valencia

University College London Hospitals Nhs Foundation Trust

Churchill Hospital

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.

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).

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