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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumors Cancer
• Intervention / Treatment: Drug: ABBV-181; Drug: ABBV-368

Detailed Description

Recruitment is closed in Part 1A; subjects are in maintenance

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Bouches-du-Rhone
    • Marseille CEDEX 05, Bouches-du-Rhone, France, 13385
      • AP-HM - Hopital de la Timone /ID# 165036
  • Ile-de-France
    • Paris CEDEX 05, Ile-de-France, France, 75248
      • Institut Curie /ID# 165038
  • Rhone
    • Lyon CEDEX 08, Rhone, France, 69373
      • Centre Leon Berard /ID# 165037
  • Val-de-Marne
    • Villejuif Cedex, Val-de-Marne, France, 94805
      • Institut Gustave Roussy /ID# 165035
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East /ID# 214530
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital /ID# 214531
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Pan American Center for Oncology Trials, LLC /ID# 213809
• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon /ID# 205999
  • Madrid, Spain, 28027
    • CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 205996
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz /ID# 211500
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia /ID# 211499
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Duran i Reynals /ID# 205997
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro, Majadahonda /ID# 206973
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 208879
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital /ID# 164002
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital /ID# 164000
  • Taipei City, Taiwan, 11031
    • Taipei Medical University Hospital /ID# 164001
• United States
  • California
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at UC San Diego /ID# 201334
    • Sacramento, California, United States, 95817
      • University of California, Davis Comprehensive Cancer Center /ID# 201342
    • Stanford, California, United States, 94305
      • Stanford University /ID# 206949
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University /ID# 207895
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute /ID# 160786
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System /ID# 160785
  • Texas
    • Dallas, Texas, United States, 75390-7208
      • University of Texas Southwestern Medical Center /ID# 201934
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics /ID# 160788
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia /ID# 212895
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists - Fairfax /ID# 160787

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1A: Monotherapy Dose Escalation; 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; Intravenous infusion
EXPERIMENTAL: Part 2A: Monotherapy Cohort Expansion; 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; Intravenous infusion
EXPERIMENTAL: Part 2B: Combination Therapy Cohort Expansion; 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-181; Intravenous infusion; Drug: ABBV-368; Intravenous infusion
EXPERIMENTAL: Part 3A: 18F-AraG Imaging Substudy in TNBC Participants; 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-181; Intravenous infusion; Drug: ABBV-368; Intravenous infusion
EXPERIMENTAL: Part 3B: 18F-AraG Imaging Substudy in HNSCC Participants; 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-181; Intravenous infusion; Drug: ABBV-368; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.	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)	CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.	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)	DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first.	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)	PFS time is defined as the time from the first dose of study drug (Day 1) to disease progression or death, whichever occurs first.	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

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 21, 2017
• Primary Completion (ACTUAL): April 13, 2022
• Study Completion (ACTUAL): April 13, 2022

Study Registration Dates

• First Submitted: March 2, 2017
• First Submitted That Met QC Criteria: March 2, 2017
• First Posted (ACTUAL): March 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 28, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Cancer; Gastric cancer; Ovarian cancer; Melanoma; Advanced Solid Tumors; Metastatic Solid Tumors; Solid Tumors; Non-small cell lung cancer (NSCLC); Cholangiocarcinoma; Mesothelioma; Triple negative breast cancer (TNBC); Small cell lung cancer (SCLC); Merkel cell carcinoma; Hepatocellular carcinoma (HCC); 2'-Deoxy-2'-[18F]Fluoro-9-β-DArabinofuranosylguanine (18F-AraG)
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: M16-074; 2016-004205-14 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No