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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04272203
• Other study ID #: M19-747
• Secondary ID: 2019-003434-16
• Status: Terminated
• Phase: Phase 1
• Start date: May 5, 2020
• Est. completion date: June 27, 2022

Study information

• Verified date: September 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: June 27, 2022
• Est. primary completion date: June 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• ABBV-184
Intravenous (IV) infusion

Locations

Country	Name	City	State
France	Hopital Saint-Andre /ID# 224218	Bordeaux
France	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	Centre Antoine Lacassagne - Nice /ID# 218014	Nice	Alpes-Maritimes
France	CHU Bordeaux - Hopital Haut Leveque /ID# 224998	Pessac	Gironde
Israel	Rambam Health Care Campus /ID# 215808	Haifa
Israel	The Chaim Sheba Medical Center /ID# 215810	Ramat Gan	Tel-Aviv
Israel	Tel Aviv Sourasky Medical Center /ID# 222749	Tel Aviv-Yafo	Tel-Aviv
Japan	National Cancer Center Hospital /ID# 216466	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East /ID# 216467	Kashiwa-shi	Chiba
Japan	Aichi Cancer Center Hospital /ID# 216469	Nagoya-shi	Aichi
United Kingdom	Cardiff & Vale University Health Board /ID# 217250	Cardiff	Wales
United Kingdom	The Christie Hospital /ID# 216118	Manchester
United Kingdom	Oxford University Hospitals NHS Foundation Trust /ID# 217252	Oxford	Oxfordshire
United States	Gabrail Cancer Center Research /ID# 215667	Canton	Ohio
United States	Fort Wayne Medical Oncology and Hematology, Inc /ID# 224332	Fort Wayne	Indiana
United States	Thomas Jefferson University /ID# 218403	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  France,  Israel,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 1 Cycle after the last participant is enrolled in dose escalation phase (Approximately 2 years)
Primary	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.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Primary	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	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	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.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Change in Laboratory Parameters	Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	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.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Change in Montreal Cognitive Assessment (MoCA)	The Montreal Cognitive Assessment (MoCA) is a one page 30-point written test that assesses cognitive function.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Change in Echocardiogram	Number of participants with abnormal change from baseline in echocardiogram will be reported.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Change in Electrocardiogram (ECG)	12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Maximum Observed Serum Concentration (Cmax) of ABBV-184	Maximum Serum Concentration (Cmax) of ABBV-184.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Time to Maximum Observed Serum Concentration (Tmax)	Time to Maximum Serum Concentration (Tmax) of ABBV-184.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Terminal Phase Elimination Rate Constant (ß) for ABBV-184	Terminal Phase Elimination Rate Constant (ß) for ABBV-184.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Terminal Phase Elimination Half-life (t1/2) of 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)
Secondary	Area Under the Serum Concentration-Time Curve 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)
Secondary	Percentage of Participants With Anti-drug Antibodies (ADAs)	Percentage of Participants With Anti-drug Antibodies (ADAs)	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	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.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	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.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	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.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Change in Bone Marrow Blast Count (Dose Expansion Phase in Participants With AML)	Percentage of blast cells in bone marrow.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	Change in Peripheral Blood Blast Count (Dose Expansion Phase in Participants With AML)	Percentage of blast cells in peripheral blood.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	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).	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	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.	Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary	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.	Up to 30 days after last participant complete study drug (Approximately 3 years)