• Signed and dated informed consent for participation in the trial obtained according to International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP), and national/local regulations.

• Male or female ≥ 18 years of age at the time of signing informed consent.

• Histological confirmation of locally advanced or metastatic, EGFR-mutant (ex19del or L858R mutations) non-small cell lung cancer (NSCLC) Stage IIIB/C or IV (AJCC 8th edition) not eligible for curative intent surgery or chemoradiation.

• Part 1\&2 Disease progression on a 3rd generation EGFR TKI-based therapy (monotherapy or in combination) received at any prior line of treatment.

• Tumor mutation profile:

• • Part 1 (backfilling component) and Part 2: Presence of C797X and absence of T790M mutations documented locally (as part of clinical practice) on a sample (blood or tissue) collected after progression on treatment with 3rd generation EGFR TKI.

• Part 1 (Backfilling component), Part 2: At least one measurable target lesion according to RECIST v1.1.

• Eastern cooperative oncology group (ECOG) performance status 0-1.

• Adequate organ function as defined below:

‣ Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L

⁃ Platelets ≥ 75 x 10\^9/L

⁃ Hemoglobin ≥ 90 g/L.

⁃ Serum total bilirubin ≤ 1.5 x ULN or ≤ 3.0 × ULN for participants with documented Gilbert's syndrome.

⁃ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN. If the participant has liver metastases, AST and ALT ≤5 × ULN.

⁃ Estimated glomerular filtration rate (GFR) ≥ 50 mL/min by CKD-EPI equation

• Adequate cardiac function as defined below:

‣ Mean QT interval corrected for heart rate according to Fridericia's formula (QTcF) value ≤ 470 msec for women and ≤ 450 msec for men and no history of long QT syndrome or risk factors for torsade de pointe.

⁃ Left ventricular ejection fraction (LVEF) ≥ 50% .

⁃ Systolic blood pressure \< 150 mmHg and diastolic blood pressure \< 100 mmHg

⁃ Female participants of childbearing potential:

∙ Negative highly sensitive serum β-HCG test performed within 7 days prior to first dose of STX-241 (C1D1) and a negative urine pregnancy test performed prior to C1D1.

‣ Agreement to use one highly effective contraceptive method (as defined in protocol and according to local regulations), starting at screening period, throughout the trial and until at least 182 days (i.e. more than 5 estimated STX- 241 half-lives (2 days) plus 6 months (180 days)) after the last dose of STX-241. If the highly effective method of contraception is a hormonal contraceptive method, it must be supplemented by one additional effective (barrier) method of contraception.

‣ Agreement to not donate eggs (ova, oocytes) for the purpose of assisted reproduction during the trial and for a period of 182 days after the last dose of STX-241.

⁃ Note: a female participant of childbearing potential is a woman who is not permanently sterilized or not postmenopausal (postmenopausal is defined as 12 months with no menses without an alternative medical cause).

⁃ Male participants/partners with female spouse/partners of childbearing potential must agree to take appropriate precautions to avoid fathering a child, i.e.:

∙ Consistently use a barrier method \[e.g., condom with spermicidal foam / gel / film /cream/suppository\], and his female partner use a highly effective method of contraception as defined in protocol and according to local regulations), starting at screening and continuing throughout the trial period and for 92 days (ie. more than 5 estimated STX-241 half-lives (2 days) plus 3 months (90 days)) after the last dose of STX-241.

‣ Not donate sperm from Day 1 (first administration of STX-241) until at least 92 days after the last dose of STX-241.

• NOTE: Other protocol defined inclusion criteria may apply.