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A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-927 and ABBV-368 With and Without ABBV-181 in Subjects With Locally Advanced or Metastatic Solid Tumors

NCT03893955

Description:

A study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-927 + ABBV-368 with and without ABBV-181 in participants with selected solid tumors. This study consists of 2 main parts, dose-escalation and dose-expansion phases. The trial will begin with dose escalation in Arm A (ABBV-927 + ABBV-368) which determines the recommended Phase 2 dose (RP2D)/maximum-tolerated dose (MTD) of ABBV-927 when administered with ABBV-368. Once the RP2D/MTD is defined in Arm A, enrollment will begin in the following arms: Arm 1 (ABBV-927 + ABBV-368) at the RP2D/MTD established in Arm A; Arm 2 (ABBV-927 + ABBV-368) at the RP2D/MTD established in Arm A; Arm B (ABBV-927 + ABBV-368 + ABBV-181) dose escalation. Once the RP2D/MTD is defined in Arm B, enrollment will begin in the following arms: Arm 3 (ABBV-927 + ABBV-368); Arm 4 (ABBV-927 + ABBV-368 + ABBV-181); Arm 5 (docetaxel).

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-927 and ABBV-368 With and Without ABBV-181 in Subjects With Locally Advanced or Metastatic Solid Tumors
  • Official Title: A Phase 1, Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-927 and ABBV-368 With and Without ABBV-181 in Subjects With Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: M19-037
  • NCT ID: NCT03893955

Conditions

  • Cancer
  • Advanced Solid Tumors
  • Triple-Negative Breast Cancer (TNBC)
  • Non-small-cell-lung-cancer (NSCLC)
  • Head and Neck Squamous Cell Carcinoma (HNSCC)
  • Metastatic Solid Tumors

Interventions

DrugSynonymsArms
ABBV-927Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid Tumors
ABBV-368Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid Tumors
ABBV-181Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC
DocetaxelTaxotere, DocefrezDose Expansion Arm 5: Docetaxel NSCLC

Purpose

A study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-927 + ABBV-368 with and without ABBV-181 in participants with selected solid tumors. This study consists of 2 main parts, dose-escalation and dose-expansion phases. The trial will begin with dose escalation in Arm A (ABBV-927 + ABBV-368) which determines the recommended Phase 2 dose (RP2D)/maximum-tolerated dose (MTD) of ABBV-927 when administered with ABBV-368. Once the RP2D/MTD is defined in Arm A, enrollment will begin in the following arms: Arm 1 (ABBV-927 + ABBV-368) at the RP2D/MTD established in Arm A; Arm 2 (ABBV-927 + ABBV-368) at the RP2D/MTD established in Arm A; Arm B (ABBV-927 + ABBV-368 + ABBV-181) dose escalation. Once the RP2D/MTD is defined in Arm B, enrollment will begin in the following arms: Arm 3 (ABBV-927 + ABBV-368); Arm 4 (ABBV-927 + ABBV-368 + ABBV-181); Arm 5 (docetaxel).

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid TumorsExperimentalSubjects with Solid Tumors will receive various doses of ABBV-927 by intravenous (IV) infusion plus ABBV-368.
  • ABBV-927
  • ABBV-368
Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLCExperimentalSubjects with non-small-cell-lung-cancer (NSCLC) will receive ABBV-927 IV at various dose levels, ABBV-368, and ABBV-181.
  • ABBV-927
  • ABBV-368
  • ABBV-181
Dose Expansion Arm 1: ABBV-927 + ABBV-368 TNBCExperimentalSubjects with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 by IV infusion at the RP2D established for Arm A plus ABBV-368.
  • ABBV-927
  • ABBV-368
Dose Expansion Arm 2: ABBV-927 + ABBV-368 HNSCCExperimentalSubjects with Head and Neck Squamous Cell Cancer (HNSCC) will receive ABBV-927 by IV at the RP2D established for Arm A plus ABBV-368.
  • ABBV-927
  • ABBV-368
Dose Expansion Arm 3: ABBV-927 + ABBV-368 NSCLCExperimentalSubjects with NSCLC will receive ABBV-927 by IV at the RP2D established for Arm B plus ABBV-368.
  • ABBV-927
  • ABBV-368
Dose Expansion Arm 4: ABBV-927 + ABBV-368 + ABBV-181 NSCLCExperimentalSubjects with NSCLC will receive ABBV-927 by IV at the RP2D established for Arm B plus ABBV-368 plus ABBV-181.
  • ABBV-927
  • ABBV-368
  • ABBV-181
Dose Expansion Arm 5: Docetaxel NSCLCExperimentalSubjects with NSCLC will receive 75 mg/m^2 by IV.
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Adequate liver, kidney and hematology function as demonstrated by laboratory values
             detailed in the study protocol.

          -  An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

        Dose-Escalation:

          -  Arm A: Participants with an advanced solid tumor who have progressed on standard
             therapies known to provide clinical benefit and/or subjects who have refused or are
             intolerant of such therapy.

          -  Arm B (non-small-cell-lung-cancer [NSCLC]): Participants with histologically or
             cytologically confirmed NSCLC who previously progressed during or after an
             anti-programmed cell death (PD)-1 or PD ligand 1 (PD-L1) therapy and a platinum-based
             regimen in the recurrent or metastatic setting.

        Dose-Expansion:

          -  Arm 1 (triple-negative breast cancer [TNBC]): Participants with confirmed breast
             adenocarcinoma that is estrogen receptor/progesterone receptor/human epidermal growth
             factor receptor (HER)2-negative who must have disease progression during or after at
             least 1 systemic therapy that included a taxane in the metastatic or recurrent setting
             and who are treatment-naïve to immunotherapy.

          -  Arm 2 (head and neck squamous cell carcinoma [HNSCC]): Participants with
             histologically or cytologically confirmed HNSCC who previously progressed during or
             after an anti-PD-1 or PD-L1 therapy and a platinum-based regimen in the recurrent or
             metastatic setting.

          -  Arms 3, 4, and 5 (NSCLC): Participants with histologically or cytologically confirmed
             NSCLC who previously progressed either during or after an anti-PD-1 or PD-L1 therapy
             and a platinum-based regimen in the recurrent or metastatic setting.

        Exclusion Criteria:

          -  Has history of inflammatory bowel disease or pneumonitis.

          -  Has uncontrolled metastases to the central nervous system.

          -  Has a concurrent malignancy that is clinically significant, treatment is required, or
             the participant is not clinically stable.

          -  Has had a major surgery ≤ 28 days prior to the first dose of study drug or the
             surgical wound is not fully healed.

          -  Has previously treated with an anti-PD- or PD-L1-targeting agent and had during the
             course of their therapy:

          -  any immune-mediated toxicity of Grade 3 or worse severity

          -  treatment of the toxicity with systemic corticosteroids

          -  any hypersensitivity to the PD-1 or PD-L1-targeting agent

          -  any treatment-related toxicity resulting in discontinuation of the PD-1 or PD-L1
             targeting agent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Expansion: Objective Response Rate (ORR)
Time Frame:Up to approximately 2 years following the first dose of study drug
Safety Issue:
Description:ORR is defined as the percentage of participants with either complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome Measures

Measure:Dose-Expansion Phase: Progression-free Survival (PFS)
Time Frame:Up to approximately 2 years since the first dose of study drug
Safety Issue:
Description:PFS is defined as the time from date of first study drug exposure to disease progression or death, whichever occurs first.
Measure:Dose-Expansion Phase: Duration of Response (DOR)
Time Frame:Up to approximately 2 years since the first dose of study drug
Safety Issue:
Description:DOR defined as the time from the participant's initial response to study drug therapy to disease progression or death, whichever occurs first.
Measure:Maximum Serum Concentration (Cmax)
Time Frame:Up to approximately 12 weeks after participant's initial dose of study drug
Safety Issue:
Description:Maximum Serum Concentration (Cmax)
Measure:Time to Maximum Observed Serum Concentration (Tmax)
Time Frame:Up to approximately 12 weeks after participant's initial dose of study drug
Safety Issue:
Description:Time to Maximum Observed Serum Concentration (Tmax)
Measure:Area Under the Serum Concentration Versus Time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCτ)
Time Frame:Up to approximately 12 weeks after participant's initial dose of study drug
Safety Issue:
Description:Area under the serum concentration versus time curve from time 0 to the time of the last measurable concentration (AUCτ).
Measure:Terminal Phase Elimination Half-life (t1/2)
Time Frame:Up to approximately 4 weeks after participant's initial dose of study drug
Safety Issue:
Description:Terminal Phase Elimination Half-life (t1/2)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AbbVie

Trial Keywords

  • Cancer
  • Advanced Solid Tumors
  • Triple-Negative Breast Cancer (TNBC)
  • Non-small-cell-lung-cancer (NSCLC)
  • Head and neck squamous cell carcinoma (HNSCC)
  • ABBV-927
  • ABBV-368
  • ABBV-181
  • metastatic solid tumors
  • dose-escalation
  • recommended phase 2 dose

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