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)

NCT02584634 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: B99910052015-001879-43JAVELIN LUNG 101
• Study Type: interventional
• Target: 43
• Locations: 5 countries
• Sites: 20

Brief Summary

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

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer; NSCLC; ALK; avelumab; crizotinib; PF-06463922

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose-limiting Toxicities (DLTs): Phase 1b

  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.

  First 2 cycles (1 cycle = 14 days)

• Percentage of Participants With Objective Response (OR): Phase 2

  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.

  Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)

• Percentage of Participants With CR for Group B: Phase 2

  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).

  Baseline up to 60 months

Secondary Outcomes (29)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  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)

• Number of Participants With Baseline Laboratory Abnormalities Grade <=2 and Post-Baseline Laboratory Abnormalities of Grades 3 or 4 Per NCI CTCAE v4.03

  Screening up to end of treatment/withdrawal (maximum of 5 years)

• Number of Participants With Vital Signs Meeting Pre-defined Criteria

  Screening up to end of treatment/withdrawal (maximum of 5 years)

• Disease Control Rate (DCR)

  Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)

• Duration of Response (DR)

  Screening, Day 1 of each cycle starting Cycle 3, up to end of treatment/withdrawal (maximum of 5 years)

Study Arms (2)

Group A

EXPERIMENTAL

ALK negative Non-Small Cell Lung Cancer

Drug: Avelumab; Drug: Crizotinib

Group B

EXPERIMENTAL

ALK positive Non-Small Cell Lung Cancer

Drug: Avelumab; Drug: PF-06463922

Interventions

Avelumab DRUG

Administered by IV once every two weeks in doses of either 5 mg/kg or 10 mg/kg

Also known as: MSB0010718C

Group A; Group B

PF-06463922 DRUG

Tablets taken orally once every day in doses of either 100mg, 75mg, or 50mg.

Group B

Crizotinib DRUG

Capsules. Taken orally once or twice every day in doses of either 200mg or 250mg.

Also known as: PF-02341066

Group A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (20)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114-2696, United States

Location

Ophthalmic Consultants of Boston Inc (OCB)

Boston, Massachusetts, 02114, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Aichi cancer center central hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, 135-8550, Japan

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Institut Catala d'Oncologia de Badalona

Badalona, Barcelona, 08916, Spain

Location

Hospital Quiron Barcelona

Barcelona, 08023, Spain

Location

Hospital Universitari de la Vall d'Hebron

Barcelona, 08035, Spain

Location

Related Publications (1)

• Solomon BJ, Dagogo-Jack I, Lee SH, Boyer MJ, Ramalingam SS, Carcereny E, Felip E, Han JY, Hida T, Hughes BGM, Kim SW, Nishio M, Seto T, Okamoto T, Zhang X, Martini JF, Wang E, De Beukelaer S, Bauer TM. Avelumab in Combination With Lorlatinib or Crizotinib in Patients With Previously Treated Advanced NSCLC: Phase 1b/2 Results From the JAVELIN Lung 101 Trial. JTO Clin Res Rep. 2024 May 16;5(7):100685. doi: 10.1016/j.jtocrr.2024.100685. eCollection 2024 Jul.

  PMID: 39034968 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

avelumab; lorlatinib; Crizotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Limitations and Caveats

Enrollment in the study was terminated early based on the changing landscape in treatment options for treatment naïve ALK positive NSCLC. This decision was not due to any safety concerns or regulatory interactions. All participants on active treatment at the time of the early enrollment termination could continue treatment and follow up per the protocol.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 22, 2015
• Study Start: December 18, 2015
• Primary Completion: February 2, 2021
• Study Completion: July 13, 2022
• Last Updated: July 7, 2023
• Results First Posted: February 9, 2022

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share

Locations

JP (3); KR (3); AU (4); US (7); ES (3)