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

NCT03071757 | Completed Phase 1 FDA Drug

• 2 other identifiers: M16-0742016-004205-14
• Study Type: interventional
• Target: 139
• Locations: 6 countries
• Sites: 27

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.

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)

Outcome Measures

Primary Outcomes (8)

• Terminal half-life (t1/2) of ABBV-368

  Terminal half-life of ABBV-368

  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

• Area under the serum concentration-time curve (AUC) of ABBV-368

  Area under the serum concentration-time curve of ABBV-368

  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

• Maximum tolerated dose (MTD) of ABBV-368 when administered as monotherapy or in combination with ABBV-181

  The MTD of ABBV-368 when administered as monotherapy or as combination therapy with ABBV-181 will be determined during the dose escalation phase of the study.

  Up to 1 year

• Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with ABBV-181

  Recommended Phase 2 dose (RPTD) for ABBV-368 when administered as monotherapy or as combination therapy with ABBV-181 will be established during the Dose expansion of the study

  Up to 18 months

• Time to Cmax (Tmax) of ABBV-368

  Time to Cmax of ABBV-368

  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

• Terminal phase elimination rate constant (β) of ABBV-368

  Terminal phase elimination rate constant of ABBV-368

  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

• Number of Participants With Adverse Events

  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. 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 subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section.

  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

• Maximum observed serum concentration (Cmax) of ABBV-368

  Maximum observed serum concentration of ABBV-368

  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 (4)

• Objective Response Rate (ORR)

  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

• Clinical benefit rate (CBR)

  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

• Duration of Objective Response (DOR)

  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

• Progression-Free Survival (PFS)

  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

Study Arms (5)

Part 1A: Monotherapy Dose Escalation

EXPERIMENTAL

Part 1A: ABBV-368 (various dose levels) intravenous administration every 2 weeks (Q2W). One cycle of treatment is 28 days, thus there will be 2 doses with ABBV-368 per cycle.

Drug: ABBV-368

Part 2A: Monotherapy Cohort Expansion

EXPERIMENTAL

Part 2A: Additional participants (triple negative breast cancer \[TNBC\]) will be enrolled in a dose expansion cohort that will further evaluate ABBV-368 (various dose levels) intravenous administration Q4W.

Drug: ABBV-368

Part 2B: Combination Therapy Cohort Expansion

EXPERIMENTAL

Part 2B: Additional participants (with Head and Neck carcinoma) will be enrolled in a dose expansion cohort that will further evaluate ABBV-368 (various dose levels) intravenous administration Q4W plus ABBV-181.

Drug: ABBV-368; Drug: ABBV-181

Part 3A: 18F-AraG Imaging Substudy in TNBC Participants

EXPERIMENTAL

Part 3A: Additional participants (with TNBC) will be enrolled in 18F-AraG Imaging Substudy that will further evaluate ABBV-368 intravenous administration Q4W plus ABBV-181.

Drug: ABBV-368; Drug: ABBV-181

Part 3B: 18F-AraG Imaging Substudy in HNSCC Participants

EXPERIMENTAL

Part 3B: Additional participants (with HNSCC) will be enrolled in 18F-AraG Imaging Substudy that will further evaluate ABBV-368 intravenous administration Q4W plus ABBV-181.

Drug: ABBV-368; Drug: ABBV-181

Interventions

ABBV-368 DRUG

Intravenous infusion

Part 1A: Monotherapy Dose Escalation; Part 2A: Monotherapy Cohort Expansion; Part 2B: Combination Therapy Cohort Expansion; Part 3A: 18F-AraG Imaging Substudy in TNBC Participants; Part 3B: 18F-AraG Imaging Substudy in HNSCC Participants

ABBV-181 DRUG

Intravenous infusion

Part 2B: Combination Therapy Cohort Expansion; Part 3A: 18F-AraG Imaging Substudy in TNBC Participants; Part 3B: 18F-AraG Imaging Substudy in HNSCC Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• A : TNBC ABBV-368 monotherapy cohorts: Subjects with locally advanced or metastatic TNBC that have exhausted standard treatment for their incurable disease.
• B : 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:
• A: 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.
• B: 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (27)

Moores Cancer Center at UC San Diego /ID# 201334

La Jolla, California, 92093, United States

Location

University of California, Davis Comprehensive Cancer Center /ID# 201342

Sacramento, California, 95817, United States

Location

Stanford University /ID# 206949

Stanford, California, 94305, United States

Location

Yale University /ID# 207895

New Haven, Connecticut, 06510, United States

Location

Carolina BioOncology Institute /ID# 160786

Huntersville, North Carolina, 28078, United States

Location

Greenville Hospital System /ID# 160785

Greenville, South Carolina, 29605, United States

Location

University of Texas Southwestern Medical Center /ID# 201934

Dallas, Texas, 75390-7208, United States

Location

South Texas Accelerated Research Therapeutics /ID# 160788

San Antonio, Texas, 78229, United States

Location

University of Virginia /ID# 212895

Charlottesville, Virginia, 22908, United States

Location

Virginia Cancer Specialists - Fairfax /ID# 160787

Fairfax, Virginia, 22031, United States

Location

AP-HM - Hopital de la Timone /ID# 165036

Marseille, Bouches-du-Rhone, 13385, France

Location

Centre Leon Berard /ID# 165037

Lyon, Rhone, 69373, France

Location

Institut Gustave Roussy /ID# 165035

Villejuif, Val-de-Marne, 94805, France

Location

Institut Curie /ID# 165038

Paris, Île-de-France Region, 75248, France

Location

National Cancer Center Hospital East /ID# 214530

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital /ID# 214531

Chuo-ku, Tokyo, 104-0045, Japan

Location

Pan American Center for Oncology Trials, LLC /ID# 213809

Rio Piedras, 00935, Puerto Rico

Location

Hospital Duran i Reynals /ID# 205997

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Puerta de Hierro, Majadahonda /ID# 206973

Majadahonda, Madrid, 28222, Spain

Location

CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 208879

Pamplona, Navarre, 31008, Spain

Location

Hospital General Universitario Gregorio Maranon /ID# 205999

Madrid, 28007, Spain

Location

CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 205996

Madrid, 28027, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz /ID# 211500

Madrid, 28040, Spain

Location

Hospital Clinico Universitario de Valencia /ID# 211499

Valencia, 46010, Spain

Location

National Cheng Kung University Hospital /ID# 164002

Tainan, 704, Taiwan

Location

National Taiwan University Hospital /ID# 164000

Taipei, 100, Taiwan

Location

Taipei Medical University Hospital /ID# 164001

Taipei, 11031, Taiwan

Location

MeSH Terms

Conditions

Neoplasms; Triple Negative Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Hepatocellular; Stomach Neoplasms; Mesothelioma; Small Cell Lung Carcinoma; Cholangiocarcinoma; Carcinoma, Merkel Cell; Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

budigalimab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Adenoma; Neoplasms, Mesothelial; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2017
• First Posted: March 7, 2017
• Study Start: March 21, 2017
• Primary Completion: April 13, 2022
• Study Completion: April 13, 2022
• Last Updated: April 28, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); ES (7); JP (2); FR (4); TW (3); US (10)