| Eligibility |
Inclusion Criteria:
1. Patients with hystologically or cythologicalconfirmed NSCLC advanced or locally
advanced disease (according to 8th version of the International Association for the
Study of Lung Cancer Staging Manual in Thoracic Oncology) not amenable to radical
treatment (IIIA, IIIB, IIIC, IV), squamous or non-squamous, recurrent after at least
one prior line.
2. The subject must be willing and able to provide written informed consent/assent for
the trial.
3. Patient must be aged = 18 years of age on day of signing informed consent.
4. Measurable disease (at least 1 lesion) based on RECIST 1.1. Patients will not be
eligible if this lesion was irradiated before inclusion.
5. Documented prior benefit (Stable Disease, Partial Response, Complete Response) to
check point PD1/PDL1 inhibitor (Nivolumab, Pembrolizumab, Durvalumab, Atezolizumab,
Avelumab or others) for at least 16 weeks (Stable Disease, Partial Response, Complete
Response) and progression while on treatment (or <12 weeks after stopping) with the
same PD-1/PD-L1 inhibitors. These patients should have received subsequent treatment
with Chemotherapy for at least 4 courses (Cohort 1) OR Documented prior benefit
(Stable Disease, Partial Response, Complete Response) to check point PD1/PDL1
inhibitor (Nivolumab, Pembrolizumab, Durvalumab, Atezolizumab, Avelumab or others) for
at least 16 weeks (Stable Disease, Partial Response, Complete Response) and
progression >12 weeks after stopping treatment (Cohort 2). No subsequent treatment
before rechallenge is allowed in this cohort
6. Patient must be willing to provide tissue from a newly obtained core or excisional
biopsy of a tumor lesion. PDL1 must be evaluable and at least 1% positive in tumor
tissue. 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. Note: If a new sample core or
excisional biopsy cannot be obtained but the patient can be included in the study and
start the treatment and the archival tumor tissue could be sent afterwards for the
central laboratory confirmation. If no previous PDL1 result is available from the
archival tissue, the patient cannot be included in the trial until central laboratory
PDL1 result is available. Other cases could be consulted with the trail chair.
7. Have a performance status of 0-1 on the ECOG Performance Scale.
8. Demonstrate adequate organ function, all screening labs should be performed within 7
days of treatment initiation.
9. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
10. Female subjects of childbearing potential must be willing to use an adequate method of
contraception (for the course of the study through 120 days after the last dose of
study medication).
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
11. 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).
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
12. All patients will be required to submit a tumor sample for PD-L1 IHC expression. If
the sample is inadequate for analysis, another sample could be provided. If a new
sample cannot be obtained due to technical or clinical reasons, archival tissue can be
sent. Other cases could be consulted with the trial chair.
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 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 TB (Bacillus Tuberculosis)
4. Hypersensitivity to pembrolizumab or any of its excipients.
5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.
6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at
baseline) from adverse events due to a previously administered agent.
Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may
qualify for the study.
Note: If subject received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.
7. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.
8. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
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.
9. 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., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
10. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Documented EGFR sensitizing mutation.
13. Documented ALK translocation.
14. 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.
15. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
16. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
19. 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.
20. Received radiation therapy to the lung of >30Gy within 6 months of the first dose of
trial treatment.
21. Evidence of interstitial lung disease.
22. Has had previously serious adverse reactions (grade 3-4) related to previous PD1/PDL1
inhibitors that preclude their treatment according to the principal investigator' s
criteria.
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