| Eligibility |
Inclusion Criteria:
- Pathologically confirmed diagnosis of malignant pleural mesothelioma
- Unresectable per thoracic surgeon assessment
- At least one prior line of systemic therapy. Note: Patients who were on prior
immunotherapy are eligible.
- ECOG 0-1
- PFTs: DLCO >40% predicted, FEV1 >50% predicted
- Male/female participants who are at least 18 years of age on the day of signing
informed consent
- Disease outside the ipsilateral thorax allowed as long as it has either been treated
definitively and been stable for 6 months
Male participants:
- A male participant must agree to use a contraception as detailed in Appendix 1 of this
protocol during the treatment period and for at least 30 days, corresponding to time
needed to eliminate any study treatment(s) (pembrolizumab and or any active
comparator/combination) plus an additional 120 days (a spermatogenesis cycle) for
study treatments with evidence of genotoxicity at any dose after the last dose of
study treatment and refrain from donating sperm during this period.
Female participants:
- A female participant is eligible to participate if she is not pregnant (see Appendix
1), not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 OR
2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 1 during the
treatment period and for at least 120 days (corresponding to time needed to
eliminate any study treatment(s) (pembrolizumab and or any active
comparator/combination) plus 30 days (a menstruation cycle) for study treatments
with risk of genotoxicity after the last dose of study treatment.
- The participant (or legally authorized representative if applicable) provides written
informed consent for the trial.
- Have a ECOG performance status of 0 to 1. Evaluation of ECOG is to be performed within
30 days prior to the date of allocation.
- Have adequate organ function as defined in the following table (Table 1). Specimens
must be collected within 45 days prior to the start of study treatment.
Table 1: Adequate Organ Function Laboratory Values
System: Hematological Absolute neutrophil count (ANC) = 1.5 K/mcL Platelets = 100 K/mcL
Hemoglobin = 9.0 g/dL
System: Renal Creatinine OR Measured or calculated^b creatinine clearance (GFR can also be
used in place of creatinine or CrCl): = 1.5 x ULN OR = 30 mL/min for participant with
creatinine levels >1.5 x institutional ULN
System: Hepatic Total bilirubin: = 1.5 x ULN OR direct bilirubin = ULN for participants
with total bilirubin levels >1.5 x ULN AST (SGOT) and ALT (SGPT): = 2.5 x ULN (= 5 x ULN
for participants with liver metastases)
ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST
(SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular
filtration rate; ULN=upper limit of normal. Criteria must be met without erythropoietin
dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
^b: Creatinine clearance (CrCl) should be calculated per institutional standard.
Note: This table includes eligibility-defining laboratory value requirements for treatment;
laboratory value requirements should be adapted according to local regulations and
guidelines for the administration of specific chemotherapies.
Exclusion Criteria:
- Newly diagnosed MPM
- Prior thoracic radiation therapy or intrapleural therapy
- Bulky disease in the fissure preventing IMPRINT
- Serious infection, concurrent active malignancies, or other serious medical illness
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
OX-40, CD137) within 4 weeks prior to study Day 1 or has not recovered (i.e., = Grade
1 at baseline) from adverse events due to a previously administered agent
- Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study treatment.
Note: Participants who have entered the follow-up phase of an investigational study may
participate as long as it has been 4 weeks after the last dose of the previous
investigational agent.
- Has a 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 study drug.
- Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,
cervical cancer in situ) that have undergone potentially curative therapy are not
excluded. Low grade malignancies not requiring active treatment are not excluded.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression, clinically stable and without
requirement of steroid treatment for at least 14 days prior to first dose of study
treatment.
- Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients.
- 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.
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
- Has a known history of Human Immunodeficiency Virus (HIV).
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
- Has undergone major surgery <4 weeks from starting pembrolizumab.
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