• Signed informed consent form

• 18 years of age or older

• Diagnosis of advanced or recurrent, histologically or cytologically confirmed metastatic or unresectable non-small cell lung cancer harboring NFE2L2 or KEAP1 alterations

• Patients must have Response Evaluation Criteria in Solid Tumors (RECIST) measurable lesions

• At the time of enrollment, patients must have experienced progression of disease following treatment with standard of care chemotherapy and immune checkpoint inhibitors either sequentially or concurrently

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

• Patient should consent to allow the acquisition of existing Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissue, as unstained slides, if available or to undergo a fresh tissue biopsy to obtain fresh tumor tissue for performance of correlative studies if deemed feasible. Tumor biopsies should only be performed if deemed safe and feasible by the investigator.

• Adequate baseline organ function:

• a) Absolute neutrophil count (ANC) ≥ 1.5x109/L (1500/uL);

• Without growth factor support for 7 days prior to screening labs for short acting growth factors and 14 days prior to screening labs for long-acting growth factors to meet eligibility

• b) Hemoglobin ≥ 9 g/dL

• Patients that require transfusion or growth factors need to demonstrate stable hemoglobin of ≥ 9 g/dL over at least a 7-day period after the last transfusion/growth factor injection prior to screening labs to meet eligibility)

• c) Platelets \>75x109/L

• No transfusion 7 days prior to screening labs to meet eligibility

• d) Hepatic

• Total bilirubin ≤1.5 x upper limit of normal (ULN) or, in patients with Gilbert syndrome, total bilirubin \>1.5 x ULN as long as direct bilirubin is normal

• PT/INR and PTT ≤1.5 x ULN, unless treated with anticoagulants

• AST(SGOT)/ALT(SGPT) ≤3 x ULN or ≤5 x ULN for patients with liver metastases/tumor infiltration

• e) Renal

• Adequate renal function as defined as Creatinine clearance ≥ 50 ml/min/1.73m2 measured or calculated by the Cockcroft-Gault equation or GFR ≥ 50 mL/min/1.73 m² by MDRD

• f) Cardiac

• Corrected QTc (Fridericia) \< 470 ms

• Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use one highly effective method of contraception, including hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy or tubal ligation; and one effective method of contraception, including male condom, female condom, cervical cap, diaphragm or contraceptive sponge or abstain from heterosexual intercourse for the duration of study participation and for 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 5 weeks after completion of DRP-104. In addition, women must refrain from donating eggs during this time.

• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of study drug plus 90 days (duration of sperm turnover) for a total of 14 weeks post completion of DRP-104. In addition, males must refrain from sperm donation during this time.

• Women must not be pregnant or breastfeeding or have intention of becoming pregnant during the study treatment or within for 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 5 weeks after completion of DRP-104.