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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Leukemia, Myeloid, Acute

Treatments: Drug: JNJ-63709178

Study type: Interventional

Funder types: Industry

Identifiers

NCT02715011

2016-000208-27 (EudraCT Number)

63709178AML1001 (Other Identifier)

CR108147

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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62 participants in 2 patient groups

Part 1: Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: JNJ-63709178

Part 2: Dose Expansion

Experimental group

Description:

Participants will receive JNJ-63709178 at the recommended Phase 2 dose(s) (RP2D) determined in dose expansion phase.

Treatment:

Drug: JNJ-63709178