A Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ABBV-927 With ABBV-368, Budigalimab (ABBV-181) and/or Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors

A Phase 1, Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Combinations of ABBV-927 With ABBV-368, Budigalimab (ABBV-181) and/or Chemotherapy in Subjects With Locally Advanced or Metastatic Solid Tumors

A study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-927 with ABBV-368, Budigalimab (ABBV-181) and/or chemotherapy in participants with selected solid tumors. This study consists of 2 main parts, a dose-escalation phase and a dose-expansion phase. The dose-expansion phase can begin once the recommended phase 2 dose/maximum tolerated dose (RP2D/MTD) is determined in the dose-escalation phase.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Advanced Solid Tumors; Metastatic Solid Tumors; Triple-Negative Breast Cancer (TNBC); Non-small-cell-lung-cancer (NSCLC)
• Intervention / Treatment: Drug: ABBV-181; Drug: ABBV-927; Drug: ABBV-368; Drug: Nab-paclitaxel; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Centre /ID# 224084
• France
  • Clermont Ferrand, France, 63011
    • Centre Jean Perrin /ID# 217911
  • Paris, France, 75018
    • AP-HP - Hopital Bichat - Claude-Bernard /ID# 212869
  • Ile-de-France
    • Paris CEDEX 05, Ile-de-France, France, 75248
      • Institut Curie /ID# 223475
  • Loire-Atlantique
    • St Herblain CEDEX, Loire-Atlantique, France, 44805
      • Institut de Cancérologie de l'Ouest René Gauducheau /ID# 212880
  • Rhone
    • Lyon CEDEX 08, Rhone, France, 69373
      • Centre Leon Berard /ID# 217910
• Israel
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 211699
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron /ID# 212804
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz /ID# 212806
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro /ID# 212805
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria /ID# 221671
• Taiwan
  • Taichung City, Taiwan, 40447
    • China Medical University Hospital /ID# 221090
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital /ID# 210993
• United States
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group, PA /ID# 218863
  • California
    • Santa Rosa, California, United States, 95403
      • St Jude Hospital dba St Joseph /ID# 211130
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University /ID# 210678
  • Florida
    • Tampa, Florida, United States, 33612-9416
      • Moffitt Cancer Center /ID# 215037
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology, Inc /ID# 226072
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University-School of Medicine /ID# 221399
  • North Carolina
    • Durham, North Carolina, United States, 27710-3000
      • Duke Cancer Center /ID# 217641
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute /ID# 210664
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Ctr /ID# 222747
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1632
      • Tennessee Oncology-Nashville Centennial /ID# 221400
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research /ID# 210716
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology /ID# 210717
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists - Fairfax /ID# 210671

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:

• 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 participants 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, 2, and 3 (triple-negative breast cancer [TNBC]): Participants with histologically or cytologically 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 4 (TNBC): Participants with histologically or cytologically confirmed TNBC who have received no previous anti-cancer therapy for TNBC, and who are PD-L1 negative on tumor tissue by immunohistochemistry (IHC) assay.
• Arm 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dose Escalation Arm A: ABBV-927 + ABBV-368 Solid Tumors; Participants with Solid Tumors will receive various doses of ABBV-927 by intravenous (IV) infusion plus ABBV-368. This will determine the recommended phase two dose (RP2D) of ABBV-927.	Drug: ABBV-927; Intravenous (IV) Infusion; Drug: ABBV-368; Intravenous (IV) Infusion
EXPERIMENTAL: Dose Escalation Arm B: ABBV-927 + ABBV-368 + ABBV-181 NSCLC; Participants with non-small-cell-lung-cancer (NSCLC) will receive ABBV-927 IV at various dose levels + ABBV-368 + ABBV-181. This will determine the recommended phase two dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181.	Drug: ABBV-181; Intravenous (IV) Infusion; Other Names: Budigalimab; Drug: ABBV-927; Intravenous (IV) Infusion; Drug: ABBV-368; Intravenous (IV) Infusion
EXPERIMENTAL: Dose Expansion Arm 1: ABBV-927 + Carboplatin + ABBV-368 TNBC; Participants with Triple Negative Breast Cancer (TNBC) will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-368 by IV.	Drug: ABBV-927; Intravenous (IV) Infusion; Drug: ABBV-368; Intravenous (IV) Infusion; Drug: Carboplatin; Intravenous (IV) Infusion
EXPERIMENTAL: Dose Expansion Arm 2: ABBV-927 + Carboplatin + ABBV-181 TNBC; Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin + ABBV-181 by IV.	Drug: ABBV-181; Intravenous (IV) Infusion; Other Names: Budigalimab; Drug: ABBV-927; Intravenous (IV) Infusion; Drug: Carboplatin; Intravenous (IV) Infusion
EXPERIMENTAL: Dose Expansion Arm 3: ABBV-927 + Carboplatin TNBC; Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Carboplatin by IV.	Drug: ABBV-927; Intravenous (IV) Infusion; Drug: Carboplatin; Intravenous (IV) Infusion
EXPERIMENTAL: Dose Expansion Arm 4: ABBV-927+ Nab-paclitaxel + ABBV-368 TNBC; Participants with TNBC will receive ABBV-927 (at the RP2D established in Arm A) + Nab-paclitaxel + ABBV-368 by IV.	Drug: ABBV-927; Intravenous (IV) Infusion; Drug: ABBV-368; Intravenous (IV) Infusion; Drug: Nab-paclitaxel; Intravenous (IV) Infusion
EXPERIMENTAL: Dose Expansion Arm 5: ABBV-927 + ABBV-368 + ABBV-181 NSCLC; Participants with NSCLC will receive ABBV-927 (at the RP2D established in Arm B) + ABBV-368 + ABBV-181 by IV.	Drug: ABBV-181; Intravenous (IV) Infusion; Other Names: Budigalimab; Drug: ABBV-927; Intravenous (IV) Infusion; Drug: ABBV-368; Intravenous (IV) Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Expansion: Objective Response Rate (ORR)	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.	Up to approximately 2 years following the first dose of study drug
Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368	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.	Up to approximately 6 months
Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181	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.	Up to approximately 6 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 21, 2019
• Primary Completion (ANTICIPATED): November 12, 2023
• Study Completion (ANTICIPATED): November 12, 2023

Study Registration Dates

• First Submitted: March 27, 2019
• First Submitted That Met QC Criteria: March 27, 2019
• First Posted (ACTUAL): March 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Cancer; Advanced Solid Tumors; metastatic solid tumors; ABBV-181; dose-escalation; recommended phase 2 dose; ABBV-927; Triple-Negative Breast Cancer (TNBC); Non-small-cell-lung-cancer (NSCLC); ABBV-368; budigalimab
• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Breast Neoplasms; Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: M19-037; 2019-000478-45 (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