Clinical trial NCT03595059: A Study With ABBV-155 Alone and in Combination With Taxane Therapy in Adults With Relapsed and/or Refractory Solid Tumors
Official title: A Phase 1 First-in-Human Study With ABBV-155 Alone and in Combination With Taxane Therapy in Adults With Relapsed and/or Refractory Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Cancer
Advanced Solid Tumors
Relapsed and/or Refractory Solid Tumors
ABBV-155
Taxane
Paclitaxel
Docetaxel
breast cancer
non-small cell lung cancer (NSCLC)
small cell lung cancer (SCLC)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2018-07-23
Enrollment: 169
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: An open-label, dose-escalation (Part 1), dose-expansion (Part 2) study to assess the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-155 alone and in combination with paclitaxel or docetaxel.

In Part 1 (dose escalation), participants will receive escalating doses of ABBV-155 monotherapy (Part 1a) or ABBV-155 in combination with paclitaxel or docetaxel (Part 1b).

In Part 2 (dose expansion), participants will receive ABBV-155 monotherapy or in combination therapy. The ABBV-155 monotherapy cohort will enroll participants with relapsed or refractory (R/R) small cell lung cancer (SCLC) (Part 2a); the ABBV-155 plus a taxane (paclitaxel or docetaxel) combination cohort will enroll participants with R/R non-small cell lung cancer (NSCLC) and breast cancer (Part 2b).

Detailed description: The Escalation cohorts (Part 1) have been completed. The expansion cohorts (Part 2) are open to enrollment.

Eligibility criteria: Inclusion Criteria:

* Has a histologic or cytologic diagnosis of a malignant solid tumor.
* Participants enrolled in Part 2a (monotherapy, dose expansion) must have small cell lung cancer (SCLC) diagnosis; participants enrolled to Part 2b (combination therapy, dose expansion) must have either NSCLC or HR-positive/HER2-negative breast cancer.
* Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
* An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
* Failure of at least 1 prior systemic chemotherapy including all available standard therapies for participants in the dose-escalation phase (Parts 1a and 1b) including the safety lead-in phase (Japan only).
* All participants with breast cancer for subjects in the dose-expansion phase (Part 2b only) must have the following:

  * Locally advanced or metastatic HR-positive/HER2-negative breast cancer after failing cyclin-dependent kinase (CDK)4/6 inhibitor-based therapy.
  * HR-positivity and HER-2-negativity should be confirmed based on American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria.
* All participants with non-small cell lung cancer (NSCLC) for participants in the dose-expansion phase (Part 2b only) must have R/R NSCLC after at least 1 line of therapy. Participants with activating mutations in EGFR, ALK/ROS1, BRAF genes, or with positive expression of PD-L1 must have been treated with the appropriate targeted therapies.
* All participants with SCLC in the dose-expansion phase (Part 2a only) must have R/R SCLC from at least 1 line of therapy which includes a platinum-based therapy with or without an anti-PD-1/PD-L1 therapy.
* All participants with either breast cancer or NSCLC must have the following if exposed to prior taxane-based therapy:

  * No history of taxane allergy (Part 1b and Part 2b only).
  * Disease that has relapsed or progressed at least 2 months after most recent exposure to any taxane-based therapy.
* Available tumor tissue suitable for immunohistochemistry testing.
* Adequate kidney, liver, and hematologic laboratory values as described in the protocol.

Exclusion Criteria:

* Untreated brain or meningeal metastases (participants with a history of metastases may be eligible based on details described in the protocol).
* Grade 2 or higher peripheral neuropathy (only applies to participants who would receive taxane therapy).
* Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
* Known active infection of hepatitis B, hepatitis C, or human immunodeficiency virus with exceptions as described in the protocol.
* Recent history (within 6 months) of congestive heart failure (defined in the protocol), ischemic cardiovascular event, cardiac arrhythmia requiring pharmacological or surgical intervention, pericardial effusion, or pericarditis.
* Any history of hypersensitivity to any ingredients of ABBV-155 will be excluded. For combination therapy only (Parts 1b and 2b), no history of serious allergic reaction to any taxane or any ingredients used in taxane formulation (e.g., cremaphor).

Primary outcomes:
measure: MTD and/or RPTD of ABBV-155
timeFrame: Up to approximately 21 days after initial dose of study drug
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 2 to 6 months
Secondary outcomes:
measure: Number of Participants with Adverse Events (AE)
timeFrame: Up to approximately 12 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 12 months
measure: Rate of Complete Response (CR)
timeFrame: Up to approximately 2 to 6 months
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 12 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 12 months after last dose of study drug
measure: Cmax of ABBV-155
timeFrame: Up to approximately 48 days
measure: Tmax of ABBV-155
timeFrame: Up to approximately 48 days
measure: Terminal Phase Elimination Rate constant of ABBV-155
timeFrame: Up to approximately 48 days
measure: AUCt of ABBV-155
timeFrame: Up to approximately 48 days
measure: AUCinf of ABBV-155
timeFrame: Up to approximately 48 days
measure: QTcF Change from Baseline
timeFrame: Up to approximately 8 days
measure: t1/2 of ABBV-155
timeFrame: Up to approximately 48 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Main /ID# 214024
state: Alabama
city: Springdale
country: United States
facility: Highlands Oncology Group, PA /ID# 201568
state: Arkansas
city: Orange
country: United States
facility: UC Irvine Medical Center - Chao Family Comprehensive Cancer Center /ID# 206105
state: California
city: West Hollywood
country: United States
facility: Duplicate_Cedars-Sinai Medical Center-West Hollywood /ID# 204267
state: California
city: Aurora
country: United States
facility: Univ of Colorado Cancer Center /ID# 208365
state: Colorado
city: New Haven
country: United States
facility: Yale University, Yale Cancer Center /ID# 201542
state: Connecticut
city: Orlando
country: United States
facility: AdventHealth Orlando /ID# 227242
state: Florida
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine /ID# 201563
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Med Cnt /ID# 215095
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital /ID# 201320
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 201564
state: Massachusetts
city: Detroit
country: United States
facility: Duplicate_Henry Ford Hospital /ID# 226852
state: Michigan
city: New Hyde Park
country: United States
facility: Northwell Health - Marcus Ave /ID# 204376
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute /ID# 201577
state: North Carolina
city: Cleveland
country: United States
facility: Univ Hosp Cleveland /ID# 201567
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma, Stephenson Cancer Center /ID# 206820
state: Oklahoma
city: Providence
country: United States
facility: Lifespan Cancer Institute at Rhode Island Hospital /ID# 204256
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center /ID# 201575
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research /ID# 214168
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center /ID# 201558
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology /ID# 204893
state: Texas
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center /ID# 241676
state: New South Wales
city: Edmonton
country: Canada
facility: Cross Cancer Institute /ID# 213838
state: Alberta
city: Toronto
country: Canada
facility: University Health Network_Princess Margaret Cancer Centre /ID# 204539
state: Ontario
city: Haifa
country: Israel
facility: Rambam Health Care Campus /ID# 230813
state: H_efa
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 230812
state: Tel-Aviv
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 215130
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 215003
state: Tokyo
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center /ID# 241095
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 240648
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum /ID# 225220
state: Limburg
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek /ID# 222260
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum /ID# 222341
state: Zuid-Holland
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht /ID# 222357
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC /ID# 232128
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 239997
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 239999
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 205673
state: Taipei
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 214062
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital /ID# 206304
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: