• Patients must have a pathologically confirmed diagnosis of NSCLC

• Patients must have progressed (clinically or radiographically) on or following prior therapy with a PD-1 or PD-L1 targeted antibody

• Patients may have only 0 or 1 intervening lines of therapy from the prior PD-(L)1 blocking therapy

• Patient must be willing and able to provide blood samples (12 green-top tubes, roughly 100mL) at the time points indicated in the Study Calendar.

• Patient must be willing and able to have core needle biopsies, or forceps biopsies if clinically feasible by (Goal 3-6 biopsies, final number to be determined by the interventionalist performing the procedure as safe) of tumor prior to initiation of dupilumab and at the on-treatment time point. Should patients undergo pre-treatment or on-treatment biopsy procedure, and inadequate number of biopsies are obtained, they may proceed with initiation/continuation of treatment at the discretion of the investigator and treating physician

• Age ≥ 18 years.

• ECOG 0-2. The exception will be patients carrying long term disability (such as cerebral palsy) where the disability is not acute nor progressive, and unlikely to significantly affect their response to therapy.

• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or

• Has not been naturally postmenopausal for at least 12 consecutive months

• Ability to understand and the willingness to sign a written informed consent.