Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    javelin lung 101
Previous Study | Return to List | Next Study

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02584634
Recruitment Status : Active, not recruiting
First Posted : October 22, 2015
Results First Posted : February 9, 2022
Last Update Posted : February 9, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

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

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Avelumab Drug: PF-06463922 Drug: Crizotinib Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 18, 2015
Actual Primary Completion Date : February 2, 2021
Estimated Study Completion Date : May 22, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Group A
ALK negative Non-Small Cell Lung Cancer
Drug: Avelumab
Administered by IV once every two weeks in doses of either 5 mg/kg or 10 mg/kg
Other Name: MSB0010718C

Drug: Crizotinib
Capsules. Taken orally once or twice every day in doses of either 200mg or 250mg.
Other Name: PF-02341066

Experimental: Group B
ALK positive Non-Small Cell Lung Cancer
Drug: Avelumab
Administered by IV once every two weeks in doses of either 5 mg/kg or 10 mg/kg
Other Name: MSB0010718C

Drug: PF-06463922
Tablets taken orally once every day in doses of either 100mg, 75mg, or 50mg.




Primary Outcome Measures :
  1. Number of Participants With Dose-limiting Toxicities (DLTs): Phase 1b [ Time Frame: First 2 cycles (1 cycle = 14 days) ]
    Any of the following adverse events (AEs) occurring during the primary DLT observation period that are attributable to one, the other, or both study drugs were classified as DLTs: Grade 4 (life-threatening) neutropenia if >7 days in duration; febrile neutropenia; Grade >=3 (severe or life threatening) neutropenic infection; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia >7 days; Grade 4 anemia; any Grade >=3 toxicity, except for any of the following: transient (<=6 hours) Grade 3 (severe) flu like symptoms or fever; transient (<=24 hours) Grade 3 fatigue, local reactions, or headache that resolved to Grade <=1 (no AE or mild AE); Grade 3 nausea and/or vomiting, diarrhea or skin toxicity that resolved to Grade <=1 within 7 days; any Grade >=3 amylase or lipase abnormality; tumor flare phenomenon; single laboratory values out of normal range that were not related to treatment, did not have any clinical correlate, and resolve to Grade <=1 within 7 days.

  2. Percentage of Participants With Objective Response (OR): Phase 2 [ Time Frame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years) ]
    OR is defined as complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 from start date (the date of first dose of study treatment) until disease progression or death due to any cause. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. Per RECIST v1.1: CR is defined as the disappearance of all target or non-target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm and all lymph nodes must be non-pathological in size (<10 mm short axis). PR is defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

  3. Percentage of Participants With CR for Group B: Phase 2 [ Time Frame: Baseline up to 60 months ]
    Per RECIST v1.1: CR is defined as the disappearance of all target or non-target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm and all lymph nodes must be non-pathological in size (<10 mm short axis).


Secondary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 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) ]
    TEAEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period. Treatment-related AEs was any untoward medical occurrence attributed to study drug in a participant who received study drug. Per NCI CTCAE v4.03: Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment; Grade 4 (Life-threatening) events caused participant to be in imminent danger of death; Grade 5 (Death) events=death related to an AE. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  2. Number of Participants With Baseline Laboratory Abnormalities Grade <=2 and Post-Baseline Laboratory Abnormalities of Grades 3 or 4 Per NCI CTCAE v4.03 [ Time Frame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years) ]
    The laboratory results were graded according to the NCI CTCAE v4.03 severity grade. Grade 1=mild AE. Grade 2=moderate AE. Grade 3=severe AE. Grade 4=life-threatening consequences; urgent intervention indicated. Shift tables were provided to examine the distribution of laboratory toxicities. The following parameters had met the criteria of CTCAE grade shift change from Grade <=2 at baseline to Grade 3 or 4 post baseline: anemia, lymphocyte count decreased, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, cholesterol high, Creatine phosphokinase (CPK) increased, Gamma glutamyl transferase (GGT) increased, hypercalcemia, hyperglycemia, hypermagnesemia, hypertriglyceridemia, hypoalbuminemia, hyponatremia, lipase increased, serum amylase increased. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.

  3. Number of Participants With Vital Signs Meeting Pre-defined Criteria [ Time Frame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years) ]
    Pre-defined criteria in vital signs: pulse rate >120 beats per minute (bpm), sitting diastolic blood pressure (DBP) increase and decrease in change from baseline of >= 20 millimeter of mercury (mmHg), sitting systolic blood pressure(SBP) < 90 mmHg, increase and decrease in change from baseline of >= 30mmHg. Baseline is defined as the last assessment prior to the date/time of the first dose of study treatment.

  4. Disease Control Rate (DCR) [ Time Frame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years) ]
    DC is defined as objective response (CR or PR) or stable disease (SD) per RECIST v.1.1 from the date of first dose of study treatment until disease progression or death due to any cause. The DCR is the proportion of patients with DC. Per RECIST v1.1: CR is defined as the disappearance of all target or non-target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to <10 mm. PR is defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as a >=20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions.

  5. Duration of Response (DR) [ Time Frame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years) ]
    DR: time from first documented occurrence of response (PR or CR) until date of first documented PD or death due to underlying cancer. Per RECIST 1.1: CR: disappearance of all non-nodal target lesions and of all non-target lesions; any pathological lymph nodes assigned as target lesions/non-target lesions have a reduction in short axis to <10 mm. PR: at least a >=30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters. PD: at least a >=20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of new lesions. Participants with no PD and were still alive by 02 Feb 2020, were censored at last adequate tumor assessment. Kaplan-Meier method was used for DR analysis.

  6. Time to Tumor Response (TTR) [ Time Frame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years) ]
    TTR is defined, for participants with an objective response (CR or PR), as the time from the start date (the date of first dose of treatment) to the first documentation of objective response (CR or PR) which is subsequently confirmed. Per RECIST v1.1: CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters.

  7. Progression-free Survival (PFS) [ Time Frame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years) ]
    PFS is defined as the time from start date (the date of first dose of treatment) to the date of the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurs first. Per RECIST v1.1: PD: a >=20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  8. Kaplan-Meier Estimates of Overall Survival (OS) [ Time Frame: Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years) ]
    OS is defined as the time from start date (the date of first dose of treatment) to the date of death due to any cause.

  9. Maximum Plasma Concentration (Cmax) of Crizotinib in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2 ]
    Cmax of crizotinib in the presence of avelumab was observed directly from data.

  10. Time to Cmax (Tmax) of Crizotinib in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2 ]
    Tmax of crizotinib in the presence of avelumab was observed directly from data as time of first occurrence.

  11. Area Under The Plasma Concentration-Time Curve During The Dosing Interval Time Course (AUCtau) of Crizotinib in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2 ]
    AUCtau of crizotinib in the presence of avelumab was caculated by Linear/Log trapezoidal method. Dose interval is defined as after single dose from time zero to the next dose (after single dose and at steady state).

  12. Apparent Plasma Clearance (CL/F) of Crizotinib in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  13. Cmax of Crizotinib Metabolite PF-06260182 in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2 ]
    Cmax of crizotinib metabolite PF-06260182 in the presence of avelumab was observed directly from data.

  14. Tmax of Crizotinib Metabolite PF-06260182 in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2 ]
    Tmax of crizotinib metabolite PF-06260182 in the presence of avelumab was observed directly from data as time of first occurrence.

  15. AUCtau of Crizotinib Metabolite PF-06260182 in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2 ]
    AUCtau of crizotinib metabolite PF-06260182 in the presence of avelumab was caculated by Linear/Log trapezoidal method. Dose interval: single dose from time zero to the next dose (after single dose and at steady state).

  16. Metabolite to Parent Ratio for AUCtau (MRAUCtau) of PF-06260182 in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2 ]
    MRAUCtau of metabolite PF-06260182 in the presence of avelumab was caculated (MRAUCtau=Metabolite AUCtau/parent AUCtau). Parent=crizotinib, metabolite=PF-06260182

  17. Metabolite to Parent Ratio for Cmax (MRCmax) of PF-06260182 in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Day 1 of Cycle 2 ]
    MRCmax of metabolite PF-06260182 in the presence of avelumab was caculated (MRCmax=Metabolite Cmax/parent Cmax). Parent=crizotinib, metabolite=PF-06260182

  18. Cmax of Lorlatinib in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2 ]
    Cmax of lorlatinib in the presence of avelumab was observed directly from data.

  19. Tmax of Lorlatinib in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2 ]
    Tmax of lorlatinib in the presence of avelumab was observed directly from data.

  20. AUCtau of Lorlatinib in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2 ]
    AUCtau of lorlatinib in the presence of avelumab was caculated by Linear/Log trapezoidal method. Dose interval: single dose from time zero to the next dose (after single dose and at steady state).

  21. 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 [ Time Frame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2 ]
    AUClast of lorlatinib in the presence of avelumab.

  22. CL/F of Lorlatinib in The Presence of Avelumab [ Time Frame: Pre-dose, 1, 2, 4, 6, 8, and 24 hours (prior to Day 2 lorlatinib dose) post dose on Day 1 of Cycle 2 ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  23. Cmax of Avelumab in The Presence of Crizotinib (Group A) or Lorlatinib (Group B) After Single Dose of Avelumab [ Time Frame: Pre-dose, 1, and 168 hours post dose of avelumab on Cycle 1 Day 1. ]
    Cmax of avelumab in the presence of crizotinib was observed directly from the data in Group A. Cmax of avelumab in the presence of lorlatinib was observed directly from the data in Group B.

  24. Cmax of Avelumab in The Presence of Crizotinib (Group A) or Lorlatinib (Group B) After Multiple Doses of Avelumab [ Time Frame: Pre-dose, 1, and 168 hours post dose of avelumab on Cycle 2 Day 1 ]
    Cmax of avelumab in the presence of crizotinib was observed directly from the data in Group A. Cmax of avelumab in the presence of lorlatinib was observed directly from the data in Group B.

  25. Trough Serum Concentration (Ctrough) of Avelumab in The Presence of Crizotinib (Group A) Following Multiple Doses of Avelumab [ Time Frame: Pre-dose on Day 1 of Cycles 2-5, 11, 17, 23, 29, 35, and 47. ]
    Ctrough is defined as predose concentration following multiple doses. Ctrough of avelumab in the presence of crizotinib was observed directly from the data in Group A.

  26. Trough Serum Concentration (Ctrough) of Avelumab in The Presence of Lorlatinib (Group B) Following Multiple Doses of Avelumab [ Time Frame: Pre-dose on Day 1 of Cycles 2-5, 11, 17, 23, 29, 35, 41, and 47. ]
    Ctrough is defined as predose concentration following multiple doses. Ctrough of avelumab in the presence of lorlatinib was observed directly from the data in Group B.

  27. Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status [ Time Frame: 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) ]
    ADA never-positive was defined as no positive ADA results at any time point. ADA ever-positive was defined as at least one positive ADA result at any time point. Baseline is defined as the last assessment on or prior to the date/time of the first dose of avelumab.

  28. Number of Participants With Positive Programmed Death Ligand-1 (PD-L1) Biomarker Expression [ Time Frame: Baseline ]
    PD-L1 protein expression is determined by using Combined Positive Score (CPS), which is the percentage of viable tumor and tumor-infiltrated immune cells (restricted to lymphocytes and macrophages) within or directly associated with tumor cell strands showing partial or complete membrane staining using the SP263 antibody. Positive is defined as CPS>=1% and negative is defined as CPS <1%.

  29. Number of Participants With Positive Tumor Infiltrating CD8+ Lymphocytes [ Time Frame: Baseline ]
    Tumor infiltrating CD8+ lymphocytes is defined as the number of CD8+ cells per unit area and the percent of counted cells. Positive is defined as >=1% and negative is defined as <1%.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02584634


Locations
Show Show 21 study locations
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] June 30, 2017
Statistical Analysis Plan  [PDF] July 12, 2019

Additional Information:
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02584634    
Other Study ID Numbers: B9991005
2015-001879-43 ( EudraCT Number )
JAVELIN LUNG 101 ( Other Identifier: Alias Study Number )
First Posted: October 22, 2015    Key Record Dates
Results First Posted: February 9, 2022
Last Update Posted: February 9, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Non-Small Cell Lung Cancer
NSCLC
ALK
avelumab
crizotinib
PF-06463922
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Avelumab
Crizotinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action