Clinical trial NCT04272203: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-02-17
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D) of ABBV-184 (Dose-Escalation Phase)
timeFrame: Up to 1 Cycle after the last participant is enrolled in dose escalation phase (Approximately 2 years)
measure: Complete Remission (CR) or Complete Remission With Partial Hematologic Recovery (CRh) Rate (Dose Expansion Phase in Participants With AML)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Objective Response Rate (ORR) (Dose Expansion Phase in Participants With NSCLC)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Change in Laboratory Parameters
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Change in Vital Signs
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Change in Montreal Cognitive Assessment (MoCA)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Change in Echocardiogram
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Change in Electrocardiogram (ECG)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Maximum Observed Serum Concentration (Cmax) of ABBV-184
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Time to Maximum Observed Serum Concentration (Tmax)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Terminal Phase Elimination Rate Constant (β) for ABBV-184
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Terminal Phase Elimination Half-life (t1/2) of ABBV-184
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Area Under the Serum Concentration-Time Curve of ABBV-184
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Percentage of Participants With Anti-drug Antibodies (ADAs)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Duration of Response (DOR) (Dose Expansion Phase)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Progression-free Survival (PFS) (Dose Expansion Phase)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Relapse-Free Survival (RFS) (Dose Expansion Phase in Participants With AML)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Change in Bone Marrow Blast Count (Dose Expansion Phase in Participants With AML)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Change in Peripheral Blood Blast Count (Dose Expansion Phase in Participants With AML)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Objective Response Rate (ORR) (Dose Expansion Phase in Participants With AML)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Rate of Conversion to Transfusion Independence (Dose Expansion Phase in Participants With AML)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
measure: Clinical Benefit Rate (CBR) (Dose Expansion Phase in Participants With NSCLC)
timeFrame: Up to 30 days after last participant complete study drug (Approximately 3 years)
Other outcomes:
Locations:
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc /ID# 224332
state: Indiana
city: Canton
country: United States
facility: Gabrail Cancer Center Research /ID# 215667
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University /ID# 218403
state: Pennsylvania
city: Nice
country: France
facility: Centre Antoine Lacassagne - Nice /ID# 218014
state: Alpes-Maritimes
city: Pessac
country: France
facility: CHU Bordeaux - Hopital Haut Leveque /ID# 224998
state: Gironde
city: Lille
country: France
facility: CHRU Lille - Hopital Claude Huriez /ID# 217508
state: Hauts-de-France
city: Nantes
country: France
facility: CHU de Nantes, Hotel Dieu -HME /ID# 215703
state: Pays-de-la-Loire
city: Bordeaux
country: France
facility: Hopital Saint-Andre /ID# 224218
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 215810
state: Tel-Aviv
city: Tel Aviv-Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 222749
state: Tel-Aviv
city: Haifa
country: Israel
facility: Rambam Health Care Campus /ID# 215808
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital /ID# 216469
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 216467
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 216466
state: Tokyo
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust /ID# 217252
state: Oxfordshire
city: Cardiff
country: United Kingdom
facility: Cardiff & Vale University Health Board /ID# 217250
state: Wales
city: Manchester
country: United Kingdom
facility: The Christie Hospital /ID# 216118
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: