Subjects will receive MK-3475 at a fixed dose of 200 mg every 3 weeks (Q3W) (Figure 1).
Subjects will be evaluated every 9 weeks (63 ± 7 days) with radiographic imaging to assess
response to treatment. QoL and Self-reported Health Questionnaires, as well as geriatric
follow-up will be performed at the same intervals. Investigators will make all
treatment-based decisions using immune-related Response Criteria (irRC). However, for
determination of overall response rate (ORR) and progression-free survival (PFS), the
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used. Adverse events will
be monitored throughout the trial and graded in severity according to the guidelines outlined
in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment with
MK-3475 will continue until two years of therapy have been administered, documented disease
progression, unacceptable adverse event(s), intercurrent illness that prevents further
administration of treatment, investigator's decision to withdraw the subject, subject
withdraws consent, noncompliance with trial treatment or procedure requirements, or
administrative reasons.
After the end of treatment, each subject will be followed for a minimum of 30 days for
adverse event monitoring (serious adverse events will be collected for up to 90 days after
the end of treatment unless the subject starts a new anticancer therapy between days 31 and
90). Subjects will have post-treatment follow-up for disease status, including initiating a
non-study cancer treatment and experiencing disease progression, until death, withdrawing
consent, or becoming lost to follow-up.
Participation in this trial will be dependent upon supplying tumor tissue from a newly
obtained formalin-fixed specimen from locations not radiated prior to biopsy. The specimen
will be evaluated at a central laboratory facility for expression status of Programmed
death-ligand 1(PD-L1) in a prospective manner. Only subjects whose tumors express Programmed
death-ligand 1(PD-L1) as determined by the central laboratory facility will be eligible for
inclusion in this study.
Inclusion Criteria:
1. Patients with histological or cytological documented stage III B or IV squamous and
non-squamous non-small-cell lung cancer previously untreated.
2. Epidermal Growth Factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK) have to
be wild-type.
3. The subject must be willing and able to provide written informed consent/assent for
the trial.
4. Patients must be aged more than 70 years, on day of signing informed consent.
5. Measurable disease (at least 1 lesion) based on RECIST criteria v1.1. Patients will
not be eligible if this lesion was irradiated before inclusion.
6. Be willing to provide tissue from a newly obtained core or excision biopsy of a tumor
lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior
to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot
be provided (e.g. inaccessible or subject safety concern) may submit an archived
specimen only upon agreement from the Sponsor.
7. PD-L1 expression ≥ 1%
8. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group
Performance Scale.
9. Screening laboratory values must meet the following criteria (Table 1, see protocol),
all screening laboratory tests should be performed within 8 days of treatment
initiation.
10. Male subjects of childbearing potential must agree to use an adequate method of
contraception, starting with the first dose of study therapy through 120 days after
the last dose of study therapy.
Exclusion Criteria:
1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose
over 10 mg of prednisone or equivalent, or any other form of immunosuppressive therapy
within 7 days prior to the first dose of trial treatment.
3. Has a known history of active Tuberculosis Bacillus
4. Hypersensitivity to Pembrolizumab or any of its excipients.
5. Has had any prior anti-cancer therapy for his or her metastatic NSCLC. In the case of
patients who have progressed to a metastatic stage after having been treated for early
stage NSCLC, chemotherapy or radiation therapy as part of this previous treatment is
allowed, provided they have been completed more than three months ago. Patients who
received adjuvant or neoadjuvant treatment or both for early stages will be eligible
for this trial. All adverse events related to these previous treatments must have
recovered (i.e., ≤ Grade 1 or at baseline).
6. Has had any previous malignancy (except non melanoma skin cancer, and cancer in situ
of: bladder, gastric, colon, cervical/dysplasia, melanoma, breast), unless a complete
remission was achieved at least 2 years prior to study entry and no additional therapy
is required or anticipated to be required during the study period.
7. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate if they
are stable (without evidence of progression by imaging 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 at a dose over 10 mg of prednisone or equivalent, for at least 7 days prior
to trial treatment. This exception does not include carcinomatous meningitis which is
excluded regardless of clinical stability.
8. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxin, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
9. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
10. Has an active infection requiring systemic therapy.
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
12. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
13. Has any geriatric exclusion criteria:
- advanced dementia (GDS ranking >6)
- moderate or severe functional dependence (Barthel Index < 35)
- Life expectancy less than one year, due to co-morbidities other than lung cancer.
14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., Hepatitis C
Virus RNA [qualitative] is detected).
16. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.
17. Evidence of interstitial lung disease.
