Perioperative Cemiplimab for Resectable Non-Small Cell Lung Cancer With High PD-L1

Inclusion criteria

• Participant is willing and able to give informed consent for participation in the trial
• Male or Female, aged 18 years or above
• ECOG 0-1
• Patient diagnosed with early-stage resectable stage II to IIIA squamous or non-squamous, operable treatment naïve NSCLC with PD-L1 TPS ≥50%. Patients who are eligible for standard of care treatment are allowed as well as those who are ineligible for chemo, if they fit the rest of the criteria
• PD-L1 TPS ≥50% as assessed by DAKO 22C3 assay
• Adequate bone marrow function, as determined by hematological parameters:

• ANC ≥1.5 x 10^9/L (1500/mm3)
• Hemoglobin ≥9.0 g/dL (5.59 mmol/L).
• Platelet count ≥75,000/mm³
• Adequate hepatic function, as determined by:

• AST/ALT for adults: AST ≤3x ULN, ALT ≤3x ULN
• Serum bilirubin ≤1.5x ULN, except in patients with clinically documented Gilbert's Syndrome where ≤3x the ULN is permitted
• Adequate kidney function as determined by serum creatinine ≤1.5x ULN OR calculated CrCl ≥50 ml/min (using the Cockcroft-Gault formula)
• Female participants of childbearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they or their partner use highly effective contraception during the trial and for 4 months thereafter*.
• Participant has clinically acceptable laboratory and ECG results (specify any other additional assessments) during screening.
• In the Investigator's opinion, is able and willing to comply with all trial requirements

• NOTE where the use of effective contraception is a protocol requirement a section on Contraception and Pregnancy should be added to the safety reporting section with corresponding information in the Participant Information Sheet.

Exclusion criteria

• Patients showing evidence of any distant metastases during screening.
• Patients with tumors with known actionable EGFR gene mutations, ALK, RET or ROS1 gene translocations
• Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study medication. Participants who require a brief course of steroids (up to 2 days in the week before enrollment) or physiologic replacement are not excluded.
• Significant renal or hepatic impairment.
• Presence of cardiovascular disease, as defined by:

a. New York Heart Association heart failure classifications of Class II, III, or IV; or myocardial infarction, or acute coronary syndrome within 12 months of first dose of study medication; or b. Transient ischemic attack or stroke within 1 year

• Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
• Participant with life expectancy of less than 6 months or is inappropriate for placebo medication.
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
• Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments within the last 2 years.

Note: The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement, or psoriasis that does not require systemic treatment.

• Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication
• Uncontrolled infection with HIV, hepatitis B or hepatitis C infection, diagnosis of immunodeficiency, and/or tuberculosis (active or latent).
• Participants with known controlled HIV infection (undetectable viral load on HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen are eligible. For these participants monitoring will be performed per local standards.
• Participants with HBsAg positive who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are eligible. Participants with controlled infections must undergo periodic monitoring of HBV DNA. Participants must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study medication.
• Participants with HBsAg negative but total HBcAb positive are permitted with the following requirements: If serum HBV DNA PCR is above the limit of detection at screening, initiate HBV antiviral therapy before study entry. If serum HBV DNA PCR is below the limit of detection, periodic monitoring of HBsAg must be performed.
• Participants who are HCV Ab+ who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are eligible
• Receipt of a live vaccine within 4 weeks of start of study medication
• Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication.
• Known hypersensitivity to the active substances or to any of the excipients.
• WOCBP* and men** who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include:

• Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening;
• Intrauterine device; intrauterine hormone-releasing system;
• Bilateral tubal occlusion/ligation;
• Vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure); and/or
• Sexual abstinence†,‡. Pregnancy testing and contraception are required for WOCBP. Pregnancy testing and contraception are not required for women who are postmenopausal or permanently sterile.

• WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the CTFG guidance. Pregnancy testing and contraception are not required for women with documents hysterectomy or tubal ligation.

• Male participants: A male participant will be excluded from the study if that participant does not agree to use condoms or practice sexual abstinence†‡, unless vasectomized, prior to the initial dose/start of study medication, during the study, and for at least 6 months after the last dose. Sperm donation is also prohibited during the same period. Vasectomy success must be confirmed by semen analysis.

• Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant.

• Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
• Participants who have participated in another research trial involving an investigational product in the past 12 weeks.