Clinical trial NCT03071757: A Study of the Safety, Tolerability and Pharmacokinetics of ABBV-368 as a Single Agent and Combination in Subjects With Locally Advanced or Metastatic Solid Tumors
Official title: A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of ABBV-368 as a Single Agent and Combination in Subjects With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors Cancer
Keywords: Solid Tumors
Cancer
Metastatic Solid Tumors
Advanced Solid Tumors
Triple negative breast cancer (TNBC)
Ovarian cancer
Hepatocellular carcinoma (HCC)
Gastric cancer
Mesothelioma
Small cell lung cancer (SCLC)
Cholangiocarcinoma
Merkel cell carcinoma
Melanoma
Non-small cell lung cancer (NSCLC)
2'-Deoxy-2'-[18F]Fluoro-9-β-DArabinofuranosylguanine (18F-AraG)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-03-07
Enrollment: 139
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: The primary purpose of this Phase 1, open-label study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of ABBV-368 as a monotherapy and in combination with ABBV-181 in participants with locally advanced or metastatic solid tumors. The study will consist of 3 parts: ABBV-368 dose escalation, ABBV-368 tumor-specific dose expansion (triple negative breast cancer \[TNBC\] cohort and head and neck cancer cohort) and 18F-AraG Imaging Substudy.

Detailed description: Recruitment is closed in Part 1A; subjects are in maintenance

Eligibility criteria: Inclusion Criteria:

* Participants must have histologic or cytology diagnosis of a known immunogenic solid tumor, as described for Part 1 Dose Escalation and Part 2 Cohort Expansion:
* Part 1 Dose Escalation:
* Participants with advanced or metastatic solid tumors that have exhausted standard treatment for their incurable disease and for whom there is currently no programmed cell death 1 (PD-1)/ programmed cell death-ligand 1 (PD-L1) approved therapy, with immunogenic type tumors such as, but not limited to triple negative breast cancer (TNBC), ovarian cancer, small cell lung cancer, mesothelioma, and cholangiocarcinoma.
* Participants who are refractory to a PD-1/PD-L1 agent, with tumor types such as melanoma, NSCLC, platinum-pretreated head and neck cancer, second line bladder and RCC.
* Part 2A and 2B Cohort Expansion:
* 2A : TNBC ABBV-368 monotherapy cohorts: Subjects with locally advanced or metastatic TNBC that have exhausted standard treatment for their incurable disease.
* 2B : Head and Neck cohort: Participants with recurrent squamous cell head and neck carcinoma that are not candidates for curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies.
* Part 3A and 3B Imaging Substudy:
* 3A: Participants with locally advanced or metastatic TNBC that have exhausted standard treatment for their incurable disease and are treatment naïve to a PD-1/PD-L1 targeting agent.
* 3B: Participants with recurrent HNSCC that are not candidates for curative treatment with local or systemic therapy, or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies. Participants must be treatment naïve to a PD-1/PD-L1 targeting agent.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
* Participants must have immune-related Response Evaluation Criteria for Solid Tumors (iRECIST) evaluable or measurable disease in the PART 1 and measurable disease per iRECIST in PART 2
* Adequate bone marrow, kidney and liver function.

Exclusion Criteria:

* Received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 21 days prior to the first dose of ABBV-368.
* Prior treatment with an OX40 targeting agent.
* has known uncontrolled metastases to the central nervous system (CNS).
* History of active autoimmune disorders and other conditions that compromise or impair the immune system.
* Confirmed positive test results for human immunodeficiency virus (HIV), or subjects with chronic or active hepatitis A, B or C. Subjects who have a history of hepatitis B or C who have documented cures after anti-viral therapy may be enrolled.
* Has received live vaccine within 28 days prior to the first dose of study drug.

Primary outcomes:
measure: Terminal half-life (t1/2) of ABBV-368
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
measure: Area under the serum concentration-time curve (AUC) of ABBV-368
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
measure: Maximum tolerated dose (MTD) of ABBV-368 when administered as monotherapy or in combination with ABBV-181
timeFrame: Up to 1 year
measure: Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with ABBV-181
timeFrame: Up to 18 months
measure: Time to Cmax (Tmax) of ABBV-368
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
measure: Terminal phase elimination rate constant (β) of ABBV-368
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
measure: Number of Participants With Adverse Events
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
measure: Maximum observed serum concentration (Cmax) of ABBV-368
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
measure: Clinical benefit rate (CBR)
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
measure: Duration of Objective Response (DOR)
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
measure: Progression-Free Survival (PFS)
timeFrame: Multiple time points in each cycle (each cycle is 28 days), throughout study completion, an average of 2 years, or participant becomes lost to follow up, or study termination
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores Cancer Center at UC San Diego /ID# 201334
state: California
city: Sacramento
country: United States
facility: University of California, Davis Comprehensive Cancer Center /ID# 201342
state: California
city: Stanford
country: United States
facility: Stanford University /ID# 206949
state: California
city: New Haven
country: United States
facility: Yale University /ID# 207895
state: Connecticut
city: Huntersville
country: United States
facility: Carolina BioOncology Institute /ID# 160786
state: North Carolina
city: Greenville
country: United States
facility: Greenville Hospital System /ID# 160785
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center /ID# 201934
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics /ID# 160788
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia /ID# 212895
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax /ID# 160787
state: Virginia
city: Marseille CEDEX 05
country: France
facility: AP-HM - Hopital de la Timone /ID# 165036
state: Bouches-du-Rhone
city: Paris CEDEX 05
country: France
facility: Institut Curie /ID# 165038
state: Ile-de-France
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 165037
state: Rhone
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 165035
state: Val-de-Marne
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 214530
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 214531
state: Tokyo
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC /ID# 213809
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Duran i Reynals /ID# 205997
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro, Majadahonda /ID# 206973
state: Madrid
city: Pamplona
country: Spain
facility: CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 208879
state: Navarra
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon /ID# 205999
city: Madrid
country: Spain
facility: CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 205996
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 211500
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia /ID# 211499
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital /ID# 164002
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 164000
city: Taipei City
country: Taiwan
facility: Taipei Medical University Hospital /ID# 164001
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: