A Study to Determine Safety, Tolerability, Pharmacokinetics, and Recommended Phase 2 Dose (RP2D) of Intravenous ABBV-184 in Adult Participants With Previously Treated Cancers

Phase 1

Terminated

• Conditions: Non Small Cell Lung Cancer; Cancer; Acute Myeloid Leukemia (AML)
• Interventions: Drug: ABBV-184

• Registration Number: NCT04272203
• Lead Sponsor: AbbVie

Brief Summary

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. This study focuses on two types of cancers: Acute Myeloid Leukemia (AML) and Non-Small Cell Lung Cancer (NSCLC). AML (blood cancer) is cancer of the white blood cells (WBC). NSCLC (solid tumor) is a disease in which cancer cells form in the tissues of the lung. The purpose of this study is to determine recommended phase 2 dose (RP2D) and to see if the study drug is safe and able to treat patients who have AML and NSCLC.

ABBV-184 is an investigational drug being developed for treatment of cancer. The study has two arms and two phases: AML arm and NSCLC arm; dose escalation and dose expansion phase. Adult participants with diagnosis of AML or NSCLC will be enrolled. In dose escalation phase, around 36 participants will be enrolled in each arm. In dose expansion phase, around 20 participants will be enrolled in each arm. The study will be conducted in approximately 50 sites across 10 countries.

Participants will receive weight based intravenous (IV) infusion of ABBV-184 once a week. At the beginning of the study, visits will occur daily during hospitalization followed by less frequently over time.

There will be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood tests, checking for side effects, and questionnaires.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-02-14
• Study First Submitted QC: 2020-02-14
• Study First Posted: 2020-02-17
• Study Start: 2020-05-05
• Primary Completion: 2022-06-27
• Study Completion: 2022-06-27
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-06
• Last Update Posted: 2022-09-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

• Diagnosis of acute myeloid leukemia (AML) or non-small cell lung cancer (NSCLC).
• Participants must consent to hospitalization for at least 72 hours following the first two doses of ABBV-184 in Cycle 1.
• Participants must have Human Leukocyte Antigen-A2 (HLA-A2) restricted genotype. Participants must be HLA-A2:01 positive in at least one allele tested with a high-resolution HLA genotyping assay performed in a College of American Pathologists (CAP)/Clinical Laboratory Improvement Act (CLIA)-certified or equivalent laboratory.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Laboratory values and cardiac function must meet the protocol specifications.

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Exclusion Criteria

• For AML participants:

  • Presence or history of extramedullary disease are ineligible, participants with a diagnosis of acute promyelocytic leukemia (APL) or BCR-ABL-positive leukemia are not eligible.

• For NSCLC participants:

  • Tumors with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) gene rearrangements are not eligible.

• Active/uncontrolled central nervous system (CNS) leukemia/lung cancer are not eligible for the study.

• History of inflammatory bowel disease, interstitial lung disease (pneumonitis), myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis, solid organ transplantation, active autoimmune disease (with exceptions of vitiligo, Type I diabetes mellitus, hypothyroidism, and psoriasis), primary immunodeficiency.

• History of clinical diagnosis of tuberculosis or major immunologic reaction to any immunoglobulin G (IgG)-containing agent are not eligible.

• Previously received anti-cancer treatment with an agent that targets the immune system by engaging cluster of differentiation 3 (CD3) are not eligible.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose Escalation: Participants With AML	ABBV-184	Participants with relapsed or refractory (R/R) AML will receive escalating doses of ABBV-184
Dose Escalation: Participants With NSCLC	ABBV-184	Participants with relapsed or refractory (R/R) NSCLC will receive escalating doses of ABBV-184
Dose Expansion: Participants With AML	ABBV-184	Participants with R/R AML will receive ABBV-184 at recommended Phase 2 dose (RP2D) determined in dose escalation phase for AML
Dose Expansion: Participants With NSCLC	ABBV-184	Participants with R/R NSCLC will receive ABBV-184 at RP2D determined in dose escalation phase for NSCLC

Primary Outcome Measures

Name	Time	Method
Recommended Phase 2 Dose (RP2D) of ABBV-184 (Dose-Escalation Phase)	Up to 1 Cycle after the last participant is enrolled in dose escalation phase (Approximately 2 years)	The RP2D of ABBV-184 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data.
Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh) Rate (Dose Expansion Phase in Participants With AML)	Up to 30 days after last participant complete study drug (Approximately 3 years)	CR/CRh rate is assessed based on the Clopper-Pearson (exact) method.
Objective Response Rate (ORR) (Dose Expansion Phase in Participants With NSCLC)	Up to 30 days after last participant complete study drug (Approximately 3 years)	ORR is defined as participants with confirmed complete or partial response (CR+PR) per RECIST, v1.1

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events (AEs)	Up to 30 days after last participant complete study drug (Approximately 3 years)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Change in Vital Signs	Up to 30 days after last participant complete study drug (Approximately 3 years)	Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.
Change in Montreal Cognitive Assessment (MoCA)	Up to 30 days after last participant complete study drug (Approximately 3 years)	The Montreal Cognitive Assessment (MoCA) is a one page 30-point written test that assesses cognitive function.
Duration of Response (DOR) (Dose Expansion Phase)	Up to 30 days after last participant complete study drug (Approximately 3 years)	DOR is defined as the time between date of first response and the first occurrence of progression or death from any cause, whichever occurs first.
Change in Laboratory Parameters	Up to 30 days after last participant complete study drug (Approximately 3 years)	Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.
Change in Echocardiogram	Up to 30 days after last participant complete study drug (Approximately 3 years)	Number of participants with abnormal change from baseline in echocardiogram will be reported.
Change in Electrocardiogram (ECG)	Up to 30 days after last participant complete study drug (Approximately 3 years)	12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.
Maximum Observed Serum Concentration (Cmax) of ABBV-184	Up to 30 days after last participant complete study drug (Approximately 3 years)	Maximum Serum Concentration (Cmax) of ABBV-184.
Time to Maximum Observed Serum Concentration (Tmax)	Up to 30 days after last participant complete study drug (Approximately 3 years)	Time to Maximum Serum Concentration (Tmax) of ABBV-184.
Terminal Phase Elimination Rate Constant (β) for ABBV-184	Up to 30 days after last participant complete study drug (Approximately 3 years)	Terminal Phase Elimination Rate Constant (β) for ABBV-184.
Terminal Phase Elimination Half-life (t1/2) of ABBV-184	Up to 30 days after last participant complete study drug (Approximately 3 years)	Terminal Phase Elimination Half-life (t1/2) of ABBV-184.
Area Under the Serum Concentration-Time Curve of ABBV-184	Up to 30 days after last participant complete study drug (Approximately 3 years)	Area Under the Serum Concentration-Time Curve of ABBV-184.
Percentage of Participants With Anti-drug Antibodies (ADAs)	Up to 30 days after last participant complete study drug (Approximately 3 years)	Percentage of Participants With Anti-drug Antibodies (ADAs)
Progression-free Survival (PFS) (Dose Expansion Phase)	Up to 30 days after last participant complete study drug (Approximately 3 years)	PFS will be defined as the time between the first dose of any study drug and the first occurrence of progression or death from any cause.
Relapse-Free Survival (RFS) (Dose Expansion Phase in Participants With AML)	Up to 30 days after last participant complete study drug (Approximately 3 years)	RFS is defined as the time between date of first response and the first occurrence of progression or death from any cause, whichever occurs first.
Change in Bone Marrow Blast Count (Dose Expansion Phase in Participants With AML)	Up to 30 days after last participant complete study drug (Approximately 3 years)	Percentage of blast cells in bone marrow.
Change in Peripheral Blood Blast Count (Dose Expansion Phase in Participants With AML)	Up to 30 days after last participant complete study drug (Approximately 3 years)	Percentage of blast cells in peripheral blood.
Objective Response Rate (ORR) (Dose Expansion Phase in Participants With AML)	Up to 30 days after last participant complete study drug (Approximately 3 years)	ORR is defined as the proportion of participants with complete remission (CR), morphologic complete remission with incomplete blood count recovery (CRi), complete remission with partial hematologic recovery (CRh), complete response with incomplete platelet recovery (CRp), and partial remission (PR).
Rate of Conversion to Transfusion Independence (Dose Expansion Phase in Participants With AML)	Up to 30 days after last participant complete study drug (Approximately 3 years)	AML participants will be considered to have converted to transfusion independence if they receive no red blood cell transfusion, platelet transfusion, or growth factors for a 56-day window after beginning study treatment.
Clinical Benefit Rate (CBR) (Dose Expansion Phase in Participants With NSCLC)	Up to 30 days after last participant complete study drug (Approximately 3 years)	CBR is defined as the proportion of participants with a CR, PR, or stable disease (SD) for at least 6 weeks by RECIST 1.1 criteria.

Trial Locations

Locations (17)

National Cancer Center Hospital East /ID# 216467; 🇯🇵 Kashiwa-shi, Chiba, Japan

Tel Aviv Sourasky Medical Center /ID# 222749; 🇮🇱 Tel Aviv-Yafo, Tel-Aviv, Israel

Hopital Saint-Andre /ID# 224218; 🇫🇷 Bordeaux, France

The Chaim Sheba Medical Center /ID# 215810; 🇮🇱 Ramat Gan, Tel-Aviv, Israel

Aichi Cancer Center Hospital /ID# 216469; 🇯🇵 Nagoya-shi, Aichi, Japan

The Christie Hospital /ID# 216118; 🇬🇧 Manchester, United Kingdom

Centre Antoine Lacassagne - Nice /ID# 218014; 🇫🇷 Nice, Alpes-Maritimes, France

CHU Bordeaux - Hopital Haut Leveque /ID# 224998; 🇫🇷 Pessac, Gironde, France

Oxford University Hospitals NHS Foundation Trust /ID# 217252; 🇬🇧 Oxford, Oxfordshire, United Kingdom

CHRU Lille - Hopital Claude Huriez /ID# 217508; 🇫🇷 Lille, Hauts-de-France, France

CHU de Nantes, Hotel Dieu -HME /ID# 215703; 🇫🇷 Nantes, Pays-de-la-Loire, France

National Cancer Center Hospital /ID# 216466; 🇯🇵 Chuo-ku, Tokyo, Japan

Thomas Jefferson University /ID# 218403; 🇺🇸 Philadelphia, Pennsylvania, United States

Fort Wayne Medical Oncology and Hematology, Inc /ID# 224332; 🇺🇸 Fort Wayne, Indiana, United States

Gabrail Cancer Center Research /ID# 215667; 🇺🇸 Canton, Ohio, United States

Rambam Health Care Campus /ID# 215808; 🇮🇱 Haifa, Israel

Cardiff & Vale University Health Board /ID# 217250; 🇬🇧 Cardiff, Wales, United Kingdom