Clinical trial NCT02988960: A Study of ABBV-927 and ABBV-181, an Immunotherapy, in Participants With Advanced Solid Tumors
Official title: A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-927 and ABBV-181, an Immunotherapy, in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors Cancer
Keywords: Non-small cell lung cancer (NSCLC)
Squamous cell carcinoma of the head and neck (SCCHN)
Advanced solid tumor
Cancer
Pancreatic adenocarcinoma
Cutaneous melanoma
ABBV-927
ABBV-181
Budigalimab
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-12-12
Enrollment: 163
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: This is a dose-escalation study designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of ABBV-927, and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 in participants with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
* Participants have adequate bone marrow, kidney and liver function.
* Participants with a history of chronic heart failure or significant cardiovascular disease must have an echocardiogram or multigated acquisition scan indicating left ventricular ejection fraction greater than or equal to 45% within 28 days prior to the first dose of study drug.
* Participants must have creatinine clearance greater than or equal to 50 mL/min as measured by 24-hour urine or estimated by the Cockcroft-Gault formula.
* Participants must have total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase and alanine aminotransferase less than or equal to 2.5 times ULN.
* Participants in all monotherapy arms 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 in all combination therapy arms must have recurrent or metastatic HNSCC or NSCLC and previously received platinum-based therapy and progressed either during or after anti-programmed death ligand 1 (PDL1)-based therapy. In addition, participants must have received only one prior immunotherapy.
* The Sponsor may decide to limit the specific tumor types selected or treatment settings for specific arms based on evidence gathered.

Exclusion Criteria:

* Participant must not have an active or prior documented autoimmune disease in the last 2 years.
* Participant must not have current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions).
* Participant must not have a history of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, previous clinical diagnosis of tuberculosis, inflammatory bowel disease, interstitial lung disease, or immune-mediated pneumonitis.
* Participant must not have a history of clinically significant uncontrolled condition(s) including but not limited to the following: uncontrolled hypertension; symptomatic congestive heart failure; unstable angina pectoris or cardiac arrhythmia including atrial fibrillation.
* Participant must not have a history of coagulopathy or a platelet disorder associated with significant clinical risk of thromboembolic event in the judgement of the investigator, or major thromboembolic event within 6 months prior to the first dose of study treatment.
* Participant must not have a prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis while receiving immunotherapy.
* Participant must not have a known uncontrolled malignancy of the central nervous system.
* Participants in all combination therapy arms must not have a history of exposure to an immunotherapy experiencing an immune-mediated adverse event that required permanent discontinuation of the immunotherapy.
* Female participants must not be pregnant, breastfeeding or considering becoming pregnant 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.
* Male participants must not be 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.
* Participant is judged by the investigator to have evidence of hemolysis.
* For Japan only, participants with a history of interstitial lung disease (pneumonitis) or current interstitial lung disease (pneumonitis).

Primary outcomes:
measure: Maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181
timeFrame: Up to 8 weeks
measure: Time to Cmax (Tmax) of ABBV-927
timeFrame: Up to 12 weeks after participant's first dose
measure: Maximum observed serum concentration (Cmax) of ABBV-927
timeFrame: Up to 12 weeks after participant's first dose
measure: Terminal-Phase Elimination Rate Constant (β) of ABBV-927
timeFrame: Up to 12 weeks after participant's first dose
measure: Terminal half-life (t1/2) of ABBV-927
timeFrame: Up to 4 weeks after participant's first dose
measure: Area under the serum concentration-time curve (AUCt) of ABBV-927
timeFrame: Up to 12 weeks after participant's first dose
measure: Time to Cmax (Tmax) of ABBV-181
timeFrame: Up to 12 weeks after participant's first dose
measure: Maximum observed serum concentration (Cmax) of ABBV-181
timeFrame: Up to 12 weeks after participant's first dose
measure: Terminal-Phase Elimination Rate Constant (β) of ABBV-181
timeFrame: Up to 12 weeks after participant's first dose
measure: Terminal half-life (t1/2) of ABBV-181
timeFrame: Up to 4 weeks after participant's first dose
measure: Area under the serum concentration-time curve (AUCt) of ABBV-181
timeFrame: Up to 12 weeks after participant's first dose
measure: Number of Participants with Adverse Events
timeFrame: Up to 30 days after and up to 24-month of treatment period
Secondary outcomes:
measure: Clinical benefit rate (CBR, defined as the percentage of participants with a confirmed partial, complete response, or stable disease for at least 24 weeks to the treatment)
timeFrame: Up to 30 days after and up to 24-month of treatment period
measure: Duration of objective response (DOR)
timeFrame: Up to 30 days after and up to 24-month of treatment period
measure: Objective response rate (ORR)
timeFrame: Up to 30 days after and up to 24-month of treatment period
measure: Progression-free survival (PFS)
timeFrame: Up to 30 days after and up to 24-month of treatment period
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Researc /ID# 156324
state: California
city: Chicago
country: United States
facility: The University of Chicago Medical Center /ID# 155264
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 155267
state: Massachusetts
city: Huntersville
country: United States
facility: Carolina BioOncology Institute /ID# 155265
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville Centennial /ID# 158654
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center /ID# 155263
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists - Fairfax /ID# 155266
state: Virginia
city: Frankston
country: Australia
facility: Peninsula Oncology Centre /ID# 164372
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health /ID# 171189
state: Victoria
city: Toronto
country: Canada
facility: University Health Network_Princess Margaret Cancer Centre /ID# 200819
state: Ontario
city: Bordeaux
country: France
facility: Institut Bergonie /ID# 162665
state: Gironde
city: Montpellier CEDEX 5
country: France
facility: Duplicate_Institut Regional du Cancer /ID# 163609
state: Herault
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 162663
state: Rhone
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 162666
state: Val-de-Marne
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 216870
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 217758
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 166291
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 166292
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda /ID# 200129
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 200128
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro /ID# 200127
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 200975
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: