Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety and tolerability of JNJ-63709178 and identify the recommended Phase 2 dose(s) (RP2D) and schedule for JNJ-63709178 in Part 1 and to characterize the safety and tolerability of JNJ-63709178 at the RP2D(s) in Part 2.

Detailed Description
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This is first-in-human (FIH) Phase 1, open-label (identity of assigned study drug will be known), multicenter, dose escalation study with dose expansion to identify the RP2D and to evaluate the safety, tolerability, and preliminary antitumor activity of JNJ-63709178 in adult participants with relapsed or refractory acute myeloid leukemia (AML) who are ineligible for or have exhausted standard therapeutic options. The study will be conducted in 2 parts: dose escalation and dose expansion. The study is divided into 3 periods: a Screening Phase (within 28 days before the first dose of study drug), a Treatment Phase (first dose of study drug until the last dose of study drug) and a Post-treatment Follow-up Phase (up to the end of study participation or end of study). Participants' safety will be monitored throughout the study.

Official Title
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A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Subjects With Relapsed or Refractory AML

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Drug: JNJ-63709178


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of acute myeloid leukemia (AML) according to the World Health Organization 2008 criteria with relapsed or refractory disease and ineligible for or have exhausted standard therapeutic options Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Hematology laboratory parameters within the Protocol specified range Chemistry laboratory parameters within the Protocol specified range A woman of childbearing potential must have a negative highly sensitive serum (beta human chorionic gonadotropin [b-hCG]) or urine test prior to the first dose of study drug Exclusion Criteria: Acute promyelocytic leukemia Active central nervous system involvement Prior solid organ transplantation Prior hematopoietic stem cell transplant within 6 months of enrollment. If the participant had an allogenic transplant there must be no apparent signs of graft versus host disease and participants must have discontinued all immunosuppressive therapies for at least 4 weeks Prior treatment with a CD123xCD3 bispecific agent, T cells expressing CD123 specific chimeric antigen receptor, or toxin-conjugated to CD123 antibodies; prior treatment with naked anti-CD123 monoclonal antibody is permitted

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation<br>Participants will receive JNJ-63709178 in Part 1 (in different cohorts). Each subsequent cohort will receive JNJ-63709178 at an increased dose level. Ascending doses may be given initially to minimize or prevent cytokine release syndrome. Dose escalation will continue until the maximum tolerated dose is reached or all planned doses are administered. | Drug: JNJ-63709178<br>* Participants will receive JNJ-63709178 in Part 1 and Part 2.<br>|
| Experimental: Part 2: Dose Expansion<br>Participants will receive JNJ-63709178 at the recommended Phase 2 dose(s) (RP2D) determined in dose expansion phase. | Drug: JNJ-63709178<br>* Participants will receive JNJ-63709178 in Part 1 and Part 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of participants with dose-limiting toxicity (DLT) |  | Up to Day 28 | 
| Part 1: Type of dose-limiting toxicity (DLT) |  | Up to Day 28 | 
| Part 2: Number of participants with adverse events and serious adverse events |  | Up to 1.5 years | 
| Part 2: Number of participants with adverse events by severity |  | Up to 1.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 2: Serum concentration of JNJ-63709178 |  | Up to 1.5 years | 
| Part 2: JNJ-63709178 Receptor occupancy |  | Up to 1.5 years | 
| Part 2: Number of participants with depletion of CD123 expressing cells |  | Up to 1.5 years | 
| Part 2: Systemic cytokine concentration |  | Up to 1.5 years | 
| Part 2: Concentration of markers of T cell activation |  | Up to 1.5 years | 
| Part 2: Anti- JNJ-63709178 antibodies concentration |  | Up to 1.5 years | 
| Part 2: Overall response rate (ORR) | ORR rate is defined as the rate of complete response (CR) plus CR with incomplete recovery (CRi) plus CR with partial hematologic recovery (CRh). | Up to 1.5 years | 
| Part 2: Event-free survival (EFS) | EFS is defined as time from start of treatment to the date of an event, that is, first documented treatment failure, relapse from CR, CRi, or CRh, or death due to any cause. | Up to 1.5 years | 
| Part 2: Relapse-free survival (RFS) | RFS is defined as time from CR, CRi, or CRh confirmed objective response to relapse from CR, CRi, or CRh or death from any cause. | Up to 1.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Myeloid, Acute, JNJ-63709178