• Age ≥18 years

• Patients with advanced NSCLC, progressing on frontline anti-PD-1/PD-L1 containing therapy (patient with rapid tumor progression will be excluded) and PDAC patients who failed one prior treatment.

• Measurable disease as defined by irRECIST criteria (See Section 7) NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; Disease that is measurable by physical examination only is not eligible.

• All patients with mutant KRAS status in either codon 12 (12A, C, D, R, S, V) or 13 (13D) will be included. The status of KRAS and LKB1 will be determined. For patients with KRAS G12C-mutated NSCLC, prior treatment with G12C-targeted therapy will be allowed; a wash-out period of 1 week from the last administration of targeted therapy would be allowed.

• Prior treatment:

‣ For NSCLC: Anti-PD1/PD-L1 containing therapy; a wash-out period of 4 weeks from the last administration of therapy would be allowed.

⁃ For PDAC: Patients who failed one prior treatment.

• Provide written informed consent.

• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

• Willingness to provide mandatory blood specimens for correlative research.

• Willingness to provide mandatory tissue specimens for correlative research.

⁃ ECOG Performance Status (PS) 0, 1 or 2.

⁃ The following laboratory values obtained ≤14 days prior to registration:

∙ Hemoglobin ≥9.0 g/dL

‣ Absolute neutrophil count (ANC) ≥1500/mm3

‣ Platelet count ≥100,000/mm3

‣ Total bilirubin ≤1.5 x ULN (upper limit of normal)

‣ ALT and AST ≤3 x ULN (≤5 x ULN for patients with liver involvement)

‣ PT (prothrombin time)/INR/aPTT (activated partial thromboplastin time) ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy

‣ Calculated creatinine clearance (CrCl) ≥20 mL/min using the Cockcroft-Gault formula

⁃ Negative pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only.