A Phase 2 Platform Study of Immunomodulatory Compounds in ICI-refractory Non-small Cell Lung Cancer

Exclusion criteria

• ✕1. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs.
• ✕2. Participants who are pregnant or breastfeeding.
• ✕3. Participants with an active, known or suspected autoimmune disease. 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.
• ✕4. Participants with a condition requiring systemic treatment with either corticosteroid (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study treatment initiation. Inhaled or topical steroids, and adrenal replacement steroid doses, are permitted in the absence of active autoimmune disease.
• ✕5. History of interstitial lung disease (ILD) or checkpoint inhibitor-induced pneumonitis.
• ✕6. Known history of positive test for human immunodeficiency virus or known acquired immunodeficiency syndrome.
• ✕7. Acute or chronic hepatitis B virus or hepatitis C virus infection. Prior viral exposure with cleared or fully treated infection based on negative HCV viral load is permitted.
• ✕8. Previous solid organ or allogeneic hematopoietic stem cell transplant.
• ✕9. Active infection requiring IV antibiotics or other uncontrolled intercurrent illness requiring hospitalization.
• ✕10. Significant cardiovascular/cerebrovascular disease, including stroke, myocardial infarction, or prolonged QTc (\> 480msec) within 3 months. Participants on beta blockers must be able to stop beta blockers for duration of their time on study treatment period when applicable.
• ✕11. Participants who have not recovered from AEs due to prior anticancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia, hearing loss, grade 2 neuropathy or endocrinopathy managed with hormone replacement therapy.
• ✕12. Participants who have previously been treated with PD-1, PD-L1, or CTLA-4 inhibitors and required permanent discontinuation or systemic immunosuppression (e.g. immune inhibitory monoclonal antibodies) due to irAEs.
• ✕13. Participants who are receiving any other investigational agents.
• ✕14. Treatment with a live, attenuated vaccine within 4 weeks prior to study treatment initiation, or anticipation of need for such a vaccine during the course of the study or within 5 months after the last dose of study treatment. Non-live COVID vaccines will be allowed on study, but it is recommended to avoid their use during the first treatment cycle (from 3 days prior to Cycle 1 Day 1 through Cycle 2 Day 3).
• ✕15. Participants must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery; 4 weeks from antibody-based therapy; 3 weeks from prior PD-(L)1 inhibitor exposure; 2 weeks or 5 half-lives (whichever is shorter) from any targeted therapy or small molecule therapy; 3 weeks or 5 half-lives (whichever is shorter) from chemotherapy or 6 weeks in the case of certain therapies (e.g., extensive radiotherapy, mitomycin C, and nitrosoureas); and 2 weeks from radiation therapy. Palliative radiotherapy is permitted for a preexisting lesion, provided it does not interfere with the assessment of tumor target lesions (e.g., the lesion to be irradiated must not be a site of measurable disease).
• ✕16. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, ductal carcinoma in situ, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
• ✕17. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
• ✕18. Inability to comply with the study and follow-up procedures.