Clinical trial NCT02955251: A Study of ABBV-428, an Immunotherapy, in Subjects With Advanced Solid Tumors
Official title: A Multi-Center, Phase 1, Open-Label, Dose-Escalation Study of ABBV-428, an Immunotherapy in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors Cancer
Keywords: Cancer
Neoplasm
Advanced solid tumor
Nivolumab
Non-small cell lung cancer (NSCLC)
Non-squamous NSCLC
Ovarian cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-11-04
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2 dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) profile of ABBV-428 when administered as monotherapy or in combination with nivolumab in participants with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Participants must have an advanced solid tumor that has progressed on standard therapies known to provide clinical benefit or the participants are intolerant to such therapies.
* Participants have adequate bone marrow, renal, hepatic and coagulation function.
* For all dose expansion arms, participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
* Participants in combination therapy cohorts must have an advanced solid tumor where the use of nivolumab is standard therapy.

Exclusion Criteria:

* Active or prior documented autoimmune disease in the last 2 years. Participants with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
* Current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions).
* History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
* Confirmed positive test results for human immunodeficiency virus (HIV), or participants with chronic or active hepatitis B or C. Participants who have a history of hepatitis B or C who have undetectable HBV DNA or HCV RNA after anti-viral therapy may be enrolled.
* Prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis (or any other unresolved or symptomatic adverse event in the last 3 months) while receiving immunotherapy.
* Male participants who are considering fathering a child or donating sperm during the study or for at least 3 or 5 months (for monotherapy and combination therapy participants, respectively) after the last dose of study drug.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: First dose of study drug through at least 100 days after end of treatment; up to 2 years after last participants first dose
measure: Recommended Phase 2 Dose (RPTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab
timeFrame: 1 day of study drug administration within the 28-day cycle at the designated cohort dose
measure: Area under the serum concentration-time curve (AUC) of ABBV-428
timeFrame: Up to 30 days after a 24-month treatment period
measure: Terminal half-life (t1/2) of ABBV-428
timeFrame: Up to 30 days after a 24-month treatment period
measure: Maximum observed serum concentration (Cmax) of ABBV-428
timeFrame: Up to 30 days after a 24-month treatment period
measure: Maximum tolerated dose (MTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab
timeFrame: Up to 2 years
measure: Time to Cmax (Tmax) of ABBV-428
timeFrame: Up to 30 days after a 24-month treatment period
Secondary outcomes:
measure: Duration of Objective Response (DOR)
timeFrame: Up to 30 days after a 24-month of treatment period
measure: Clinical benefit rate (CBR)
timeFrame: Up to 30 days after a 24-month of treatment period
measure: Progression-Free Survival (PFS)
timeFrame: Up to 30 days after a 24-month of treatment period
measure: Objective Response Rate (ORR)
timeFrame: Up to 30 days after a 24-month of treatment period
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Pima /ID# 155461
state: Arizona
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center - Main /ID# 154439
state: California
city: Chicago
country: United States
facility: University of Chicago /ID# 154440
state: Illinois
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center /ID# 170665
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Hospital System /ID# 154437
state: South Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center at Texas Medical Center /ID# 154441
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics /ID# 154442
state: Texas
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse /ID# 163131
state: New South Wales
city: St Leonards
country: Australia
facility: Northern Cancer Institute /ID# 163132
state: New South Wales
city: Bordeaux
country: France
facility: Institut Bergonie /ID# 202391
state: Gironde
city: Paris CEDEX 05
country: France
facility: Institut Curie /ID# 162258
state: Ile-de-France
city: Villejuif
country: France
facility: Gustave Roussy /ID# 162257
state: Ile-de-France
city: Marseille CEDEX 05
country: France
facility: Hopital de la Timone /ID# 162256
state: Provence-Alpes-Cote-d Azur
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 168072
state: Rhone
city: Taipei City
country: Taiwan
facility: National Taiwan Univ Hosp /ID# 169034
state: Taipei
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Luke JJ, Barlesi F, Chung K, Tolcher AW, Kelly K, Hollebecque A, Le Tourneau C, Subbiah V, Tsai F, Kao S, Cassier PA, Khasraw M, Kindler HL, Fang H, Fan F, Allaire K, Patel M, Ye S, Chao DT, Henner WR, Hayflick JS, McDevitt MA, Fong L. Phase I study of ABBV-428, a mesothelin-CD40 bispecific, in patients with advanced solid tumors. J Immunother Cancer. 2021 Feb;9(2):e002015. doi: 10.1136/jitc-2020-002015.