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Phase I

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

  • Study HIC#:2000025780
  • Last Updated:07/22/2020

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).

  • Start Date01/12/2020
  • End Date05/10/2023

Trial Purpose and Description

Primary Outcome Measures  :

  1. Dose Expansion: Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 years following the first dose of study drug ]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.
  2. Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368 [ Time Frame: Up to approximately 6 months ]The RP2D of ABBV-927 + ABBV-368 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics data.
  3. Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181 [ Time Frame: Up to approximately 6 months ]The RP2D of ABBV-927 + ABBV-368 + ABBV-181 will be determined during the dose-escalation phase of the study. RP2D will be determined using available safety and pharmacokinetics data.

Secondary Outcome Measures  :

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

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:
    1. any immune-mediated toxicity of Grade 3 or worse severity
    2. treatment of the toxicity with systemic corticosteroids
    3. any hypersensitivity to the PD-1 or PD-L1-targeting agent
    4. any treatment-related toxicity resulting in discontinuation of the PD-1 or PD-L1 targeting agent

Sub-Investigators

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