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

Primary Purpose

Acute Myeloid Leukemia (AML), Non Small Cell Lung Cancer, Cancer

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

ABBV-184

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Advanced Solid Tumors Cancer, Acute Myeloid Leukemia (AML), Non Small Cell Lung Cancer (NSCLC), Blood Cancer, ABBV-184, Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Dose Escalation: Participants With AML

Dose Escalation: Participants With NSCLC

Dose Expansion: Participants With AML

Dose Expansion: Participants With NSCLC

Arm Description

Participants with relapsed or refractory (R/R) AML will receive escalating doses of ABBV-184

Participants with relapsed or refractory (R/R) NSCLC will receive escalating doses of ABBV-184

Participants with R/R AML will receive ABBV-184 at recommended Phase 2 dose (RP2D) determined in dose escalation phase for AML

Participants with R/R NSCLC will receive ABBV-184 at RP2D determined in dose escalation phase for NSCLC

Outcomes

Primary Outcome Measures

Recommended Phase 2 Dose (RP2D) of ABBV-184 (Dose-Escalation Phase)

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)

CR/CRh rate is assessed based on the Clopper-Pearson (exact) method.

Objective Response Rate (ORR) (Dose Expansion Phase in Participants With NSCLC)

ORR is defined as participants with confirmed complete or partial response (CR+PR) per RECIST, v1.1

Secondary Outcome Measures

Number of Participants with Adverse Events (AEs)

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 Laboratory Parameters

Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.

Change in Vital Signs

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)

The Montreal Cognitive Assessment (MoCA) is a one page 30-point written test that assesses cognitive function.

Change in Echocardiogram

Number of participants with abnormal change from baseline in echocardiogram will be reported.

Change in Electrocardiogram (ECG)

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

Maximum Serum Concentration (Cmax) of ABBV-184.

Time to Maximum Observed Serum Concentration (Tmax)

Time to Maximum Serum Concentration (Tmax) of ABBV-184.

Terminal Phase Elimination Rate Constant (β) for ABBV-184

Terminal Phase Elimination Rate Constant (β) for ABBV-184.

Terminal Phase Elimination Half-life (t1/2) of ABBV-184

Terminal Phase Elimination Half-life (t1/2) of ABBV-184.

Area Under the Serum Concentration-Time Curve of ABBV-184

Area Under the Serum Concentration-Time Curve of ABBV-184.

Percentage of Participants With Anti-drug Antibodies (ADAs)

Duration of Response (DOR) (Dose Expansion Phase)

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.

Progression-free Survival (PFS) (Dose Expansion Phase)

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)

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)

Percentage of blast cells in bone marrow.

Change in Peripheral Blood Blast Count (Dose Expansion Phase in Participants With AML)

Percentage of blast cells in peripheral blood.

Objective Response Rate (ORR) (Dose Expansion Phase in Participants With AML)

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)

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)

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.

Full Information

NCT ID

NCT04272203

First Posted

February 14, 2020

Last Updated

September 6, 2022

Sponsor

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT04272203

Brief Title

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

Official Title

A Phase 1 First in Human, Multicenter, Open-Label Dose-Escalation Study to Determine the Safety, Tolerability, Pharmacokinetics, and RP2D of ABBV-184 in Subjects With Previously Treated Cancers

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Terminated

Why Stopped

Strategic considerations

Study Start Date

May 5, 2020 (Actual)

Primary Completion Date

June 27, 2022 (Actual)

Study Completion Date

June 27, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbbVie

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia (AML), Non Small Cell Lung Cancer, Cancer

Keywords

Advanced Solid Tumors Cancer, Acute Myeloid Leukemia (AML), Non Small Cell Lung Cancer (NSCLC), Blood Cancer, ABBV-184, Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Escalation: Participants With AML

Arm Type

Experimental

Arm Description

Participants with relapsed or refractory (R/R) AML will receive escalating doses of ABBV-184

Arm Title

Dose Escalation: Participants With NSCLC

Arm Type

Experimental

Arm Description

Participants with relapsed or refractory (R/R) NSCLC will receive escalating doses of ABBV-184

Arm Title

Dose Expansion: Participants With AML

Arm Type

Experimental

Arm Description

Participants with R/R AML will receive ABBV-184 at recommended Phase 2 dose (RP2D) determined in dose escalation phase for AML

Arm Title

Dose Expansion: Participants With NSCLC

Arm Type

Experimental

Arm Description

Participants with R/R NSCLC will receive ABBV-184 at RP2D determined in dose escalation phase for NSCLC

Intervention Type

Drug

Intervention Name(s)

ABBV-184

Intervention Description

Intravenous (IV) infusion

Primary Outcome Measure Information:

Title

Recommended Phase 2 Dose (RP2D) of ABBV-184 (Dose-Escalation Phase)

Description

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.

Time Frame

Up to 1 Cycle after the last participant is enrolled in dose escalation phase (Approximately 2 years)

Title

Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh) Rate (Dose Expansion Phase in Participants With AML)

Description

CR/CRh rate is assessed based on the Clopper-Pearson (exact) method.

Time Frame