This is an open label, multi-center, Phase 1/2 study evaluating the safety, tolerability, PK, PD, and preliminary efficacy (antitumor activity) of BBT-207. It will consist of 3 parts; dose escalation, recommended phase 2 dose selection, and dose expansion.

Inclusion Criteria:

1. Histologically or cytologically confirmed Stage III (locally advanced) NSCLC not amenable to curative therapy or stage IV NSCLC.

2. Patients must have received treatment with at least 1 third-generation EGFR TKI (eg, Osimertinib, Lazertinib).

3. Confirmation that the tumor harbors an EGFR mutation as follows:

   1. Phase 1a (Dose Escalation): Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (exon 19 deletion or L858R).
   2. Phase 1b (RP2D Selection): Have complex EGFR mutations containing C797S confirmed.
   3. Phase 2 (Dose Expansion): Have complex EGFR mutations containing C797S confirmed by a central laboratory.

4. Documented partial or complete response (CR) or durable (at least 16 weeks) stable disease, based on the RECIST criteria, after treatment of an EGFR TKI.

5. Radiological documentation of disease progression or intolerance to a previous continuous (at least 30 days) treatment with an approved EGFR TKI therapy (including, but not limited to osimertinib, afatinib, dacomitinib, gefitinib, or erlotinib).

6. All patients must have documented radiological progression or intolerance to the last treatment administered prior to enrolling in the study.

7. Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

8. Adequate organ function test result.

9. All standard therapeutic options have been exhausted, refused by the patient, or are contraindicated; or the patient is deemed by the investigator not to be an appropriate candidate for standard-of-care treatment (as defined in the country of participation).

Exclusion Criteria:

1. Has symptomatic brain or spinal cord metastases with exceptions.

2. Any of the following cardiac conditions within the last 6 months from the first dose of study treatment:

   1. Unexplained or cardiovascular cause of presyncope or syncope, tachycardia, ventricular fibrillation, or sudden cardiac arrest.
   2. Prolonged corrected QT interval (mean resting corrected QT interval using Fridericia's formula [QTcF] >470 msec from 3 ECGs).
   3. Clinically significant, uncontrolled, cardiovascular disease including congestive heart failure grade 3 or 4 according to the New York Heart Association classification; myocardial infarction or unstable angina, uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias, including bradyarrhythmia that may cause QT prolongation (eg, Type II second degree heart block or third-degree heart block).

   <Prior or Concomitant Anticancer Therapy>

3. An EGFR TKI, including but not limited to osimertinib, afatinib, dacomitinib, gefitinib, or erlotinib within 8 days of the first dose of study treatment.

4. Small molecule targeted inhibitor other than EGFR inhibitor class or cytotoxic chemotherapy within 14 days, or biologic anticancer medicine (cytokines or antibodies, etc.) within 28 days (before the initiation of BBT-207 treatment) for the systemic treatment of advanced NSCLC.

5. Has toxicities from previous anticancer therapies that have not resolved to baseline levels or to CTCAE grade ≤1, with the exception of alopecia and peripheral neuropathy.

6. Has had radiotherapy within 14 days before the initiation of study treatment. Note: Palliative radiotherapy for pain can be administered at any time before the first dose of study treatment.