A phase II study that tests afatinib in combination with pembrolizumab in patients with squamous cell carcinoma of the lung

Phase 1

Conditions: locally advanced or metastatic squamous cell carcinoma of the lung
MedDRA version: 20.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-005042-37-ES

Lead Sponsor: Boehringer Ingelheim España, S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 28

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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 4.2.2.1) 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 absorptio

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: 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.;Primary end point(s): 1) Objective Response (OR), defined as best overall response of complete response (CR) or partial response (PR);Timepoint(s) of evaluation of this end point: 1) Up to two years

Secondary Outcome Measures

Name	Time	Method

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