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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

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: M16-074
  • SECONDARY ID: 2016-004205-14
  • NCT ID: NCT03071757

Conditions

  • Advanced Solid Tumors Cancer

Interventions

DrugSynonymsArms
ABBV-368Part 3A: 18F-AraG Imaging Substudy in TNBC Participants
ABBV-181Part 3A: 18F-AraG Imaging Substudy in TNBC Participants

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
Part 1A: Monotherapy Dose EscalationExperimentalPart 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.
  • ABBV-368
Part 2A: Monotherapy Cohort ExpansionExperimentalPart 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.
  • ABBV-368
Part 2B: Combination Therapy Cohort ExpansionExperimentalPart 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.
  • ABBV-368
  • ABBV-181
Part 3A: 18F-AraG Imaging Substudy in TNBC ParticipantsExperimentalPart 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.
  • ABBV-368
  • ABBV-181
Part 3B: 18F-AraG Imaging Substudy in HNSCC ParticipantsExperimentalPart 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.
  • ABBV-368
  • ABBV-181

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Terminal half-life (t1/2) of ABBV-368
Time Frame: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
Safety Issue:
Description:Terminal half-life of ABBV-368

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AbbVie

Trial 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)

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