Testing Afatinib in Combination With Pembrolizumab in Patients With Squamous Cell Carcinoma of the Lung (LUX-Lung IO)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03157089
Recruitment Status : Recruiting
First Posted : May 17, 2017
Last Update Posted : December 11, 2018
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

The main objective is to assess the efficacy of afatinib in combination with pembrolizumab, as measured by objective response (OR) in patients with locally advanced or metastatic squamous NSCLC who progressed during or after first line platinum-based treatment.

The secondary objectives are to confirm the RP2D, assess the safety profile, and the secondary measures of clinical efficacy including disease control (DC), duration of objective response (DoR), progression-free survival (PFS), overall survival (OS), and tumour shrinkage.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Afatinib Drug: pembrolizumab Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Afatinib in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Squamous Cell Carcinoma of the Lung
Actual Study Start Date : November 2, 2017
Estimated Primary Completion Date : July 29, 2019
Estimated Study Completion Date : October 9, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: All patients Drug: Afatinib
Film-coated tablet

Drug: pembrolizumab
Solution for infusion
Other Name: KEYTRUDA®

Primary Outcome Measures :
  1. Objective Response (OR) [ Time Frame: Up to two years ]
    defined as best overall response of complete response (CR) or partial response (PR)

Secondary Outcome Measures :
  1. Disease control (DC) [ Time Frame: Up to two years after last patient entered ]
    defined as best overall response of CR, PR, or stable disease (SD)

  2. Duration of objective response (DoR) [ Time Frame: Up to two years after last patient entered ]
    defined as the time from first documented CR or PR until the earliest of disease progression or death among patients with OR.

  3. Progression-free survival (PFS) [ Time Frame: Up to two years after last patient entered ]
    defined as the time from first drug intake until disease progression or death from any cause, whichever occurs earlier.

  4. Overall survival (OS) [ Time Frame: Up to two years after last patient entered ]
    defined as time from first drug intake until death from any cause.

  5. Tumour shrinkage (in millimeters) [ Time Frame: Up to two years after last patient entered ]
    defined as the difference between the minimum post-baseline sum of diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of diameters of the same set of target lesions.

  6. Recommended Phase II Dose (RP2D) [ Time Frame: Up to two years after last patient entered ]
    defined as the dose confirmed by the Safety Monitoring Committee (SMC) for patients to obtain as starting dose for the combination therapy of afatinib and pembrolizumab.

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

Inclusion Criteria:

  • Pathologically confirmed diagnosis of NSCLC considered to be of squamous histology, including mixed histology, in the opinion of the investigator.
  • Locally advanced (stage IIIb) or metastatic (stage IV) NSCLC not considered eligible for curative therapy.
  • Documented disease progression or relapse (based on investigator's assessment) during or after completion of at least 2 cycles of platinum-based chemotherapy as first line treatment of Stage IIIB/IV SCC of the lung. This includes patients relapsing within 6 months of completing (neo)adjuvant/curative-intent chemotherapy or definitive chemoradiotherapy. Patients should be eligible to receive 2nd line therapy in the opinion of the investigator.
  • At least one target lesion (outside the brain) that can be accurately measured per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. In patients who only have one target lesion and a biopsy of the lesion is required; the baseline imaging must be performed at least two weeks after the biopsy.
  • Availability and willingness to provide a fresh tumour tissue sample obtained after relapse or progression on or after prior therapy. In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen may be submitted.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate organ function (all screening labs should be performed within 10 days prior to treatment initiation).
  • Recovery from major surgery or any previous anti-cancer or radiation therapy-related toxicity to ≤ CTCAE Grade 1 at C1_V1 (except for alopecia; stable sensory neuropathy must be ≤ CTCAE Grade 2).
  • At least 18 years of age or over the legal age of consent in countries where that is greater than 18 years at screening.
  • Signed and dated written informed consent in accordance with ICHGCP and local legislation prior to admission to the trial.
  • Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly, starting with the screening visit and through 120 days after the last dose of pembrolizumab treatment and 2 weeks after last afatinib treatment, respectively, as listed in the protocol. A list of contraception methods meeting these criteria is provided in the patient information. -- Note: Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to taking study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible.

Exclusion criteria:

  • Prior therapy with any immune checkpoint inhibitor; however, prior (neo) adjuvant checkpoint inhibitor therapy is allowed if completed at least 12 months before relapse.
  • Prior therapy with EGFR inhibiting drugs; however, prior EGFR-targeted (neo) adjuvant therapy is allowed if completed at least 12 months before relapse.
  • Treatment with prior chemotherapy, non-EGFR targeted therapy, or anti-cancer hormonal treatment within 2 weeks prior to the first dose of trial treatment.
  • Current or previous treatment with experimental therapy or use of an investigational device within 30 days prior to the first dose of trial treatment.
  • Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of trial treatment.
  • Received a live vaccine within 30 days prior to the first dose of trial treatment. Seasonal flu vaccines that do not contain live virus are permitted.
  • Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids is allowed.
  • Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of the efficacy and safety of the test drugs.
  • Radiotherapy within 4 weeks prior to start of treatment except as follows:

    • Palliative radiotherapy to regions other than the chest is allowed up to 2 weeks prior to start of treatment;
    • Single dose palliative radiotherapy for symptomatic metastasis within 2 weeks prior to start of treatment may be allowed but must be agreed with the Sponsor.
  • Major surgery (according to the investigator's assessment) performed within 4 weeks prior to start of treatment or planned during the projected course of the study.
  • Requirement or wish to continue the intake of restricted medications (see Section or any drug considered likely to interfere with the safe conduct of the trial.
  • Known history of hypersensitivity to afatinib or any of its excipients.
  • Known history of hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

    -- Note: Patients with previously treated brain metastases may participate provided they are stable without evidence of progression by imaging (using the identical imaging modality for each assessment, either MRI or CT scan) for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, systemic corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids or current ILD/pneumonitis.
  • Any history or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of the study drug (e.g. nausea, vomiting, Crohn's disease, ulcerative colitis, chronic diarrhoea, malabsorption) in the opinion of the investigator.
  • Active infectious disease requiring intravenous systemic therapy or which puts the patient at increased risk in the opinion of the investigator.
  • Previous or concomitant malignancies at other sites than the lung, except:

    • Effectively treated non-melanoma skin cancers;
    • Effectively treated carcinoma in situ of the cervix;
    • Effectively treated ductal carcinoma in situ;
    • Other effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.
  • Known human immunodeficiency virus (HIV) (HIV 1/2 antibodies), active hepatitis B (e.g. HBsAg reactive) or hepatitis C (e.g. HCV RNA [qualitative] is detected).
  • History of active TB (Bacillus Tuberculosis).
  • History or presence of cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of ≥3, unstable angina or poorly controlled arrhythmia which are considered as clinically relevant by the investigator. Myocardial infarction within 6 months prior to start of treatment.
  • Psychiatric, substance abuse disorders, or chronic alcohol abuse or any condition as per investigator's opinion.
  • Further criteria apply, some were shortened.

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 identifier (NCT number): NCT03157089

Contact: Boehringer Ingelheim 1-800-243-0127

United States, California
University of California Davis Recruiting
Sacramento, California, United States, 95817
Contact: Jonathan Riess    +001 (916) 734-3772   
United States, District of Columbia
Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital Recruiting
Washington, District of Columbia, United States, 20016
Contact: Benjamin Levy    +001 (202) 660-6500   
United States, Florida
Florida Hospital Recruiting
Orlando, Florida, United States, 32804
Contact: Tarek Mekhail    +001 (407) 303-3235   
United States, Kentucky
Baptist Health Medical Group Recruiting
Lexington, Kentucky, United States, 40503
Contact: Firas Badin    +001 (859) 276-0414   
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89128
Contact: Brian Vicuna    +001 (702) 952-2140   
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10021
Contact: Ronald Scheff    +001 (646) 962-2066   
United States, Washington
Cancer Care Northwest Centers, PS Recruiting
Spokane Valley, Washington, United States, 99216
Contact: Srivalli Gopaluni    +001 (509) 228-1000   
HOP Côte de Nacre Recruiting
Caen, France, 14033
Contact: Jeannick Madelaine    +33 (0)2 31 06 46 76   
HOP Le Mans Recruiting
Le Mans, France, 72037
Contact: Olivier Molinier    +33 (0)2 43 43 24 50   
HOP Nord Recruiting
Marseille, France, 13015
Contact: Fabrice Barlesi    +33 (0)4 91 38 56 28   
HOP Nord Laënnec Recruiting
Nantes, France, 44093
Contact: Jaafar Bennouna    +33 (0)2 40 67 99 93   
HOP Sainte Musse Recruiting
Toulon, France, 83100
Contact: Clarisse Audigier-Valette    +33 (0)4 94 14 56 10   
Korea, Republic of
Severance Hospital Recruiting
Seoul, Korea, Republic of, 03722
Contact: Hye Ryun Kim    82 2 2228 8125   
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Contact: Sang-We Kim    82 2 3010 3215   
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Enriqueta Felip    +34932746077   
Complejo Hospitalario Universitario Insular - Materno Infantil Recruiting
Las Palmas de Gran Canaria, Spain, 35016
Contact: Delvys Rodríguez Abreu    +34928441738   
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Luis Paz-Ares Rodríguez    +34913908349   
Hospital Clínico Universitario Lozano Blesa Recruiting
Zaragoza, Spain, 50009
Contact: Dolores Isla    +34976765746   
Hacettepe Universitesi Tip Fakultesi, Onkoloji ABD Active, not recruiting
Ankara, Turkey, 06230
Istanbul Universitesi Cerrahpasa Tip Fakultesi Completed
Istanbul, Turkey, 34098
Sponsors and Collaborators
Boehringer Ingelheim

Responsible Party: Boehringer Ingelheim Identifier: NCT03157089     History of Changes
Other Study ID Numbers: 1200-0283
2016-005042-37 ( EudraCT Number )
First Posted: May 17, 2017    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents