Cemiplimab for Clinical Stage I, 2-3.9cm, Non-Small Cell Lung Cancer

Inclusion criteria

• Participants must have histologically proven NSCLC, clinically staged cT1c or T2a, clinically node-negative (no bronchoscopy is required for screening) using AJCC 9th Edition.
• Participants must have an SUVmax >6.2 on standard of care staging PET scan, and/or biopsy histology must be consistent with moderate/poorly/or undifferentiated NSCLC.
• Participants must have pulmonary function study capable of tolerating the proposed lung resection according to the surgeon. This will require post-operative predicted forced expiratory volume (FEV) 1 and diffusing capacity of the lungs for carbon monoxide (DLCO) greater than 40%.
• Participants must be deemed a surgical candidate with adequate organ function, documented in the electronic medical record (EMR).
• Participants must have ECOG Performance status 0-1.
• Participants must have a signed and dated IRB approved written consent form before the performance of any protocol related procedures that are not part of the normal participant care.
• Participants must be aged >18 years old.

Exclusion criteria

• Participants must have no known ALK driver mutations
• Participants must have no known EGFR mutations.
• Participants must not have known or suspected active autoimmune disease requiring systemic immunosuppressive treatment within the past two years. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Participants must not have any condition treated with chemotherapy or other cancer therapy, including anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T-cell co-regulatory pathways).
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• Participants must not have history of symptomatic interstitial lung disease.
• Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness will be excluded from the study.
• Participants must not have previous history of bone marrow transplant.
• Participants must not have a known allergy, or history of allergy or hypersensitivity to study drug or any of the excipients.
• 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.

• Any condition that requires ongoing/continuous corticosteroid or immunosuppressive 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.
• Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication.
• Known infection with HIV, hepatitis B or hepatitis C infection, diagnosis of immunodeficiency, and/or tuberculosis (active or latent).
• Exclusions relating to vaccines:

a) Receipt of a live vaccine within 4 weeks of start of study medication. b) 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.

• Exclusions and information relating to pregnancy/contraception:

• 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:

i. 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; ii. Intrauterine device; intrauterine hormone-releasing system; iii. Bilateral tubal occlusion/ligation; iv. 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 v. Sexual abstinence†,‡.

Note: 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 documented 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.