RBN-2397 in Combination With Pembrolizumab in Patients With SCCL

Inclusion Criteria:

1. Confirmed diagnosis of advanced/metastatic NSCLC of squamous cell histology asdetermined by local testing practices.
2. Patients should have received prior therapy including a platinum containingchemotherapy regimen and an ICI, including anti-PD-1/anti-PD-L1, anti-cytotoxicT-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, either sequentially or ascombination of chemo + checkpoint inhibitor.
3. The last regimen prior to enrolling in the study must be a checkpointinhibitor-containing regimen where the best response for at least one tumor responseassessment was stable disease (SD), partial response (PR), or complete response (CR).
4. Patients experienced PD as determined by the investigator during or following theirmost recent treatment regimen
5. Must agree to undergo tumor biopsy if medically safe and feasible. Archival biopsysamples may be submitted if fresh biopsy can't be obtained.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
7. CT or MRI imaging done within 28 days prior to study treatment and have at least onemeasurable target lesion
8. Normal organ and bone marrow function
9. Patient and his/her partner agree to use adequate contraception during and for 3months after the last study drug dose

Exclusion Criteria:

1. Has non-squamous histology NSCLC. Patients whose tumors have a mixed histology areineligible.
2. Patient should not have received more than two prior lines of therapy with ICIincluding anti-PD-1/anti-PD-L1, anti-CTLA-4 inhibitors and one prior line of achemotherapy treatment.
3. Patient is unable to swallow oral medications, has impairment of gastrointestinal (GI)function or GI disease that may significantly alter drug absorption (e.g., activeinflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorptionsyndrome).
4. Prior radiation within 2 weeks of Cycle 1 Day 1 (C1D1), except for palliativeradiotherapy to a limited field. Patients must have recovered from all radiationrelated toxicities, not require corticosteroids, and not have had radiationpneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks ofradiotherapy) to non CNS disease.
5. A patient with CNS metastases is excluded if:

• Has active CNS metastases (new lesions or progression from prior imaging study)requiring treatment within 28 days prior to study treatment and/or ongoingcorticosteroid therapy.
• Has symptomatic or untreated leptomeningeal disease.

6. Patients who discontinue prior treatment with an ICI due to irAEs.
7. Has a known history of prior malignancy within the last 5 years. Except: malignanciesthat were treated curatively and have not recurred within 2 years prior to studytreatment; completely resected basal cell and squamous cell skin cancers; anymalignancy considered to be indolent and that has never required therapy; andcompletely resected carcinoma in situ of any type.
8. Has received a live-virus vaccination within 30 days of planned treatment start.Vaccines that do not contain live virus are permitted.
9. Any of the following in the previous 6 months: myocardial infarction or currenthistory of New York heart Association (NYHA) Class III or IV heart failure,uncontrolled angina, severe uncontrolled ventricular anemias, or electrocardiographicevidence of acute ischemia.
10. Patient has a history of prolonged QT syndrome or Torsades de pointes, and/or has afamilial history of prolonged QT syndrome.
11. Patient is taking a concomitant medication that is a strong inhibitor or inducer ofcytochrome P450 [CYP]-mediated metabolism or that is metabolized by CYP 2B6, 3A4 or 2C19, 2C9, or other members of the IIC subfamily of the CYP genes and that, ifunderdosed, would constitute a significant risk to the patient. Individual cases maybe discussed with the Medical Monitor.
12. Ingestion of herbal medicines and grapefruit, grapefruit juice, pomegranate juice,star fruit, or orange marmalade (made with Seville oranges) from the start of thescreening period. (Note that there are well- reported cases of CYP3A drug-druginteractions with these foodstuffs.)
13. Has active autoimmune disease that has required systemic treatment in the past 12months (i.e., with use of disease modifying agents, corticosteroids orimmunosuppressive drugs). Replacement therapy (e.g., ≤ 10 mg daily prednisolone orsteroid equivalent, thyroxine, insulin, or corticosteroid replacement therapy foradrenal or pituitary insufficiency, etc.) is not considered a form of systemictreatment. Patients with vitiligo, resolved childhood asthma/atopy, type I diabetesmellitus, and residual hypothyroidism due to an autoimmune condition and onlyrequiring hormone replacement, are not excluded.
14. Is on chronic systemic steroids (e.g., > 10 mg daily prednisolone or steroidequivalent for > 6 months). Subjects with asthma that require intermittent use ofbronchodilators, inhaled steroids, or local steroid injections would not be excludedfrom the study.
15. Has an active systemic infection requiring therapy (e.g.: bacterial, fungal, viral).
16. Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positiveHBsAg result. Active Hepatitis C is defined by a known positive Hepatitis C Antibodyresult and known quantitative hepatitis C virus ribonucleic acid (RNA) results greaterthan the lower limits of detection of the assay.
17. Has known psychiatric or substance abuse disorder that would interfere withcooperation with the requirements of the trial.
18. Has interstitial lung disease or a history of pneumonitis that required oral orintravenous steroids to assist with management. Lymphangitic spread of the NSCLC isnot exclusionary.
19. Is pregnant or breastfeeding or expecting to conceive or father children while onstudy medication and for the required duration of contraception after the last dose ofstudy medication.
20. Has ongoing acute clinical AEs of National Cancer Institute (NCI) Common TerminologyCriteria for Adverse Events (CTCAE) Grade ≥2 resulting from prior cancer therapies (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ Grade 3).
21. Has had, within the past 6 months, the occurrence of one or more of the followingevents: cerebrovascular accident, deep vein thrombosis, pulmonary embolism, hemorrhage (CTCAE Grade 3 or 4), chronic liver disease (meeting criteria for Child Pugh Class Bor C), organ transplantation.
22. Has, within 2 weeks prior to Day 1, received systemic therapeutic doses ofcorticosteroids (e.g., > 10 mg daily prednisolone or steroid equivalent). Topical,inhaled, nasal and ophthalmic steroids are allowed for short term treatment of acuteconditions (e.g.: asthma, poison ivy contact dermatitis); for other immunosuppressiveagents, the exclusionary dose and duration will be determined in consultation with theMedical Monitor.
23. Has any other medical or personal condition that, in the opinion of the Investigator,may potentially compromise the safety or compliance of the patient, or may precludethe patient's successful completion of the clinical study.