Testing Afatinib in Combination With Pembrolizumab in Patients With Squamous Cell Carcinoma of the Lung

NCT03157089 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 1200-02832016-005042-37PN497
• Study Type: interventional
• Target: 24
• Locations: 5 countries
• Sites: 13

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective response rate is defined as percentage of participants with the best overall response of complete response (CR, disappearance of all target lesions) or confirmed partial response (PR, at least a 30% decrease in sum of diameter (SoD, longest diameter (LD) measured for all lesions except lymph nodes, where shortest diameter (ShD) was used) of target lesions, reference is baseline SoD). Tumour response was assessed based on local radiological image (Computerised tomography (CT) or Magnetic resonance imaging (MRI)) evaluation by the investigators according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.

  Tumour assessment performed at screening (-28 days), week 9 (day 56-63) after study treatment (afatinib or pembrolizumab) start and every 9th week thereafter, up to 556 days.

Secondary Outcomes (6)

• Recommended Phase II Dose (RP2D)

  21 days (1 treatment cycle) from study treatment (afatinib and pembrolizumab) administration.

• Disease Control Rate (DCR)

  Tumour assessment performed at screening (-28 days), week 9 (day 56-63) after study treatment (afatinib or pembrolizumab) start and every 9th week thereafter, up to 556 days.

• Duration of Objective Response (DOR)

  Tumour assessment performed at screening (-28 days), week 9 (day 56-63) after study treatment (afatinib or pembrolizumab) start and every 9th week thereafter, up to 436 days.

• Progression-free Survival (PFS)

  Tumour assessment performed at screening (-28 days), week 9 (day 56-63) after study treatment (afatinib or pembrolizumab) start and every 9th week thereafter, up to 556 days.

• Overall Survival (OS)

  From Day 1 of study treatment (afatinib or pembrolizumab) administration up to a total of 574 days.

Study Arms (1)

All patients

EXPERIMENTAL

Drug: Afatinib; Drug: pembrolizumab

Interventions

Afatinib DRUG

Film-coated tablet

Also known as: GILOTRIF, GIOTRIF, XOVOLTIB

All patients

pembrolizumab DRUG

Solution for infusion

Also known as: KEYTRUDA®

All patients

Eligibility Criteria

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

You may qualify if:

• 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 ICH-GCP 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.

You may not qualify if:

• 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 chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) 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 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (13)

Baptist Health Medical Group

Lexington, Kentucky, 40503, United States

Location

HOP Côte de Nacre

Caen, 14033, France

Location

HOP Le Mans

Le Mans, 72037, France

Location

HOP Nord

Marseille, 13015, France

Location

HOP Nord Laënnec

Nantes, 44093, France

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Complejo Hospitalario Universitario Insular - Materno Infantil

Las Palmas de Gran Canaria, 35016, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Hacettepe Universitesi Tip Fakultesi, Onkoloji ABD

Ankara, 06230, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa Tip Fakultesi

Istanbul, 34098, Turkey (Türkiye)

Location

Related Publications (2)

• Levy B, Barlesi F, Paz-Ares L, Bennouna J, Erman M, Felip E, Isla D, Ryun Kim H, Kim SW, Madelaine J, Molinier O, Ozguroglu M, Rodriguez Abreu D, Adeniji A, Lorence RM, Voccia I, Chisamore MJ, Riess JW. Phase II study of afatinib plus pembrolizumab in patients with squamous cell carcinoma of the lung following progression during or after first-line chemotherapy (LUX-Lung-IO). Lung Cancer. 2022 Apr;166:107-113. doi: 10.1016/j.lungcan.2022.01.023. Epub 2022 Feb 3.

  PMID: 35257949 DERIVED

• Levy B, Paz-Ares L, Bennouna J, Felip E, Abreu DR, Isla D, Barlesi F, Molinier O, Madelaine J, Audigier-Valette C, Kim SW, Kim HR, Ozguroglu M, Erman M, Badin FB, Mekhail TM, Scheff R, Chisamore MJ, Sadrolhefazi B, Riess JW. Afatinib With Pembrolizumab for Treatment of Patients With Locally Advanced/Metastatic Squamous Cell Carcinoma of the Lung: The LUX-Lung IO/KEYNOTE 497 Study Protocol. Clin Lung Cancer. 2019 May;20(3):e407-e412. doi: 10.1016/j.cllc.2018.12.022. Epub 2019 Jan 4.

  PMID: 30808583 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib; pembrolizumab

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)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

After the safety run-in, the SMC decided that the benefit-risk ratio was not favorable and recommended ending the trial according to a protocol-defined option. Trial was completed as described in protocol.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 17, 2017
• Study Start: November 2, 2017
• Primary Completion: January 13, 2020
• Study Completion: January 13, 2020
• Last Updated: February 23, 2021
• Results First Posted: February 23, 2021

Record last verified: 2021-02

Locations

FR (4); KR (2); TU (2); US (1); ES (4)