Clinical trial NCT03893955: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Cancer
Advanced Solid Tumors
Triple-Negative Breast Cancer (TNBC)
Non-small-cell-lung-cancer (NSCLC)
Metastatic Solid Tumors
Keywords: Cancer
Advanced Solid Tumors
Triple-Negative Breast Cancer (TNBC)
Non-small-cell-lung-cancer (NSCLC)
ABBV-927
ABBV-368
ABBV-181
metastatic solid tumors
dose-escalation
recommended phase 2 dose
budigalimab
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2019-03-28
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


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 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

Primary outcomes:
measure: Dose Expansion: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years following the first dose of study drug
measure: Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368
timeFrame: Up to approximately 6 months
measure: Dose-Escalation Phase: Recommended Phase 2 Dose (RP2D) of ABBV-927 + ABBV-368 + ABBV-181
timeFrame: Up to approximately 6 months
Secondary outcomes:
measure: Dose-Expansion Phase: Progression-free Survival (PFS)
timeFrame: Up to approximately 2 years since the first dose of study drug
measure: Dose-Expansion Phase: Duration of Response (DOR)
timeFrame: Up to approximately 2 years since the first dose of study drug
measure: Maximum Serum Concentration (Cmax)
timeFrame: Up to approximately 12 weeks after participant's initial dose of study drug
measure: Time to Maximum Observed Serum Concentration (Tmax)
timeFrame: Up to approximately 12 weeks after participant's initial dose of study drug
measure: Area Under the Serum Concentration Versus Time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCτ)
timeFrame: Up to approximately 12 weeks after participant's initial dose of study drug
measure: Terminal Phase Elimination Half-life (t1/2)
timeFrame: Up to approximately 4 weeks after participant's initial dose of study drug
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group, PA /ID# 218863
state: Arkansas
city: Santa Rosa
country: United States
facility: St Jude Hospital dba St Joseph /ID# 211130
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine /ID# 210678
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center /ID# 215037
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc /ID# 226072
state: Indiana
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 221399
state: Missouri
city: Durham
country: United States
facility: Duke Cancer Center /ID# 217641
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute /ID# 210664
state: North Carolina
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Ctr /ID# 222747
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville Centennial /ID# 221400
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research /ID# 210716
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology /ID# 210717
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax /ID# 210671
state: Virginia
city: South Brisbane
country: Australia
facility: Icon Cancer Centre /ID# 224084
state: Queensland
city: St Herblain CEDEX
country: France
facility: Institut de Cancérologie de l'Ouest René Gauducheau /ID# 212880
state: Loire-Atlantique
city: Paris CEDEX 05
country: France
facility: Institut Curie /ID# 223475
state: Paris
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 217910
state: Rhone
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin /ID# 217911
city: Paris
country: France
facility: AP-HP - Hopital Bichat - Claude-Bernard /ID# 212869
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 211699
state: Tel-Aviv
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 212804
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 212806
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro /ID# 212805
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria /ID# 221671
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 210993
state: Taipei
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 221090
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: