Clinical trial NCT02584634: Study to Evaluate Safety, Efficacy, Pharmacokinetics And Pharmacodynamics Of Avelumab In Combination With Either Crizotinib Or PF-06463922 In Patients With NSCLC. (Javelin Lung 101)
Official title: A PHASE 1B/2, OPEN-LABEL, DOSE-FINDING STUDY TO EVALUATE SAFETY, EFFICACY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AVELUMAB (MSB0010718C) IN COMBINATION WITH EITHER CRIZOTINIB OR PF-06463922 IN PATIENTS WITH ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
NSCLC
ALK
avelumab
crizotinib
PF-06463922
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-10-22
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of avelumab when combined with either crizotinib or PF-06463922.

Detailed description: This is a Phase 1b/2, open label, multi center, multiple dose, safety, pharmacokinetic and pharmacodynamic study of Group A and Group B in cohorts of adult patients with locally advanced or metastatic NSCLC.

Eligibility criteria: * Inclusion Criteria
* Diagnosis of advanced or metastatic NSCLC. Group A must be ALK negative NSCLC and Group B must be ALK positive NSCLC
* Group A at least one prior regimen of therapy
* Group B any number of prior regimens.
* Mandatory tumor tissue available
* At least one measurable lesion
* ECOG Performance status 0 or 1
* Adequate bone marrow, renal, liver and pancreatic function
* Negative pregnancy test for females of childbearing potential
* Group B Phase 2: No prior systemic treatment for advanced or metastatic disease (adjuvant and/or neoadjuvant therapies are allowed if completed at least 6 months prior to study entry. No prior tyrosine kinase inhibitor therapy is allowed at any time prior to study entry)

Exclusion Criteria:

* No prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody.
* No Severe or Chronic medical conditions including gastrointestinal abnormalities or significant cardiac history
* No active infection requiring systemic therapy
* Prior organ transplantation including allogenic stem cell transplantation.

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLTs): Phase 1b
timeFrame: First 2 cycles (1 cycle = 14 days)
measure: Percentage of Participants With Objective Response (OR): Phase 2
timeFrame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
measure: Percentage of Participants With CR for Group B: Phase 2
timeFrame: Baseline up to 60 months
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 30 days after last dose of study treatment or the day before start day of new anti-cancer therapy (maximum of 5 years)
measure: Number of Participants With Baseline Laboratory Abnormalities Grade <=2 and Post-Baseline Laboratory Abnormalities of Grades 3 or 4 Per NCI CTCAE v4.03
timeFrame: Screening up to end of treatment/withdrawal (maximum of 5 years)
measure: Number of Participants With Vital Signs Meeting Pre-defined Criteria
timeFrame: Screening up to end of treatment/withdrawal (maximum of 5 years)
measure: Disease Control Rate (DCR)
timeFrame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
measure: Duration of Response (DR)
timeFrame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
measure: Time to Tumor Response (TTR)
timeFrame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
measure: Progression-free Survival (PFS)
timeFrame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
measure: Kaplan-Meier Estimates of Overall Survival (OS)
timeFrame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)
measure: Maximum Plasma Concentration (Cmax) of Crizotinib in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
measure: Time to Cmax (Tmax) of Crizotinib in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
measure: Area Under The Plasma Concentration-Time Curve During The Dosing Interval Time Course (AUCtau) of Crizotinib in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
measure: Apparent Plasma Clearance (CL/F) of Crizotinib in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
measure: Cmax of Crizotinib Metabolite PF-06260182 in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
measure: Tmax of Crizotinib Metabolite PF-06260182 in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
measure: AUCtau of Crizotinib Metabolite PF-06260182 in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
measure: Metabolite to Parent Ratio for AUCtau (MRAUCtau) of PF-06260182 in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
measure: Metabolite to Parent Ratio for Cmax (MRCmax) of PF-06260182 in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2
measure: Cmax of Lorlatinib in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
measure: Tmax of Lorlatinib in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
measure: AUCtau of Lorlatinib in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
measure: Area Under The Plasma Concentration Time Curve From Time of Dosing to The Last Collection Time Point (AUClast) of Lorlatinib in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
measure: CL/F of Lorlatinib in The Presence of Avelumab
timeFrame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2
measure: Cmax of Avelumab in The Presence of Crizotinib (Group A) or Lorlatinib (Group B) After Single Dose of Avelumab
timeFrame: Pre-dose, 1, and 168 hours post dose of avelumab on Cycle 1 Day 1.
measure: Cmax of Avelumab in The Presence of Crizotinib (Group A) or Lorlatinib (Group B) After Multiple Doses of Avelumab
timeFrame: Pre-dose, 1, and 168 hours post dose of avelumab on Cycle 2 Day 1
measure: Trough Serum Concentration (Ctrough) of Avelumab in The Presence of Crizotinib (Group A) Following Multiple Doses of Avelumab
timeFrame: Pre-dose on Day 1 of Cycles 2-5, 11, 17, 23, 29, 35, and 47.
measure: Trough Serum Concentration (Ctrough) of Avelumab in The Presence of Lorlatinib (Group B) Following Multiple Doses of Avelumab
timeFrame: Pre-dose on Day 1 of Cycles 2-5, 11, 17, 23, 29, 35, 41, and 47.
measure: Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
timeFrame: Day 1 of Cycles 1-5, then every 12 weeks thereafter, end of treatment/withdrawal, and 30 days after last avelumab dose (up to a maximum of 5 years)
measure: Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression
timeFrame: Baseline
measure: Number of Participants With Positive Tumor Infiltrating CD8+ Lymphocytes
timeFrame: Baseline
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston Inc (OCB)
state: Massachusetts
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Nagoya
country: Japan
facility: Aichi cancer center central hospital
state: Aichi
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Koto-ku, Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Goyang-Si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Badalona
country: Spain
facility: Institut Catala d'Oncologia de Badalona
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Quiron Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari de la Vall d'Hebron
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: