PH009-1 in Patients With EGFR Mutation Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

A Phase I/IIa, Open-label, Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Preliminary Anti-tumor Activity of PH009-1 in Patients With EGFR Mutation Locally Advanced or Metastatic NSCLC

The study will contain three stages: Phase I includes dose escalation phase (i.e., phase Ia) and dose expansion phase (i.e., phase Ib). Once the dosage regimen is confirmed, the sponsor can decide to start the cohort expansion phase (i.e., phase IIa)

phase Ia (Dose Escalation Phase) Approximately 17-96 subjects will be enrolled, dose escalation will be implemented by combining accelerated escalation with "3+3" design and safety evaluation requirements as specified. The total number of the subjects will depend upon the number of dose escalation necessary.

Phase Ib (Dose Expansion Phase): 2 to 3 doses selected from escalation doses, up to 20 subjects (subjects in dose escalation are involved) will be enrolled in each expansion arm, the total number of subjects will depend upon the number of dose expansions, expansions may adjusted depends upon the emerging data.

Phase IIa (Cohort Expansion): Approximately 20 subjects will be enrolled in each expansion cohort. Sample size may be adjusted based on emerging data.

Inclusion Criteria:

1. Age ≥18 years, signed informed consent form before any trial-related processes.
2. Histological or cytological confirmed diagnosis of unresectable locally advanced or metastatic NSCLC.
3. Subjects must have NSCLC harboring one or more active EGFR mutations.
4. patients must have at least one measurable tumor lesion per RECIST v1.1 criteria as per Investigator's assessment.
5. The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1.
6. Life expectancy ≥12 weeks.
7. Adequate hematologic and organ function per protocol.
8. WOCBP must have a negative serum and/or urine pregnancy test result within 7 days prior to the first dose of PH009-1.

Exclusion Criteria:

1. Treatment with any of the following:

   Prior treatment with an EGFR-TKI within 8 days prior to the first dose of PH009-1; Prior treatment with immunotherapy or biotherapy within 4 weeks prior to the first dose of PH009-1; Radiotherapy (palliative radiotherapy completed at least 2 weeks prior to the first dose of Ph009-1 can be enrolled) within 4 weeks prior to the first dose of PH009-1; Herbal therapy that has anti-tumor effects within 2 weeks prior to the first dose of PH009-1; Mitomycin and nitrosourea within 6 weeks prior to the first dose of PH009-1; Oral fluorouracil such as tegafur and capecitabine within 2 weeks prior to the first dose of PH009-1; Chemotherapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs), or other anti-tumor drugs for the treatment of NSCLC within 4 weeks prior to the first dose of PH009-1. Marketed and/or experimental drug treatment for EGFR C797S mutations.

2. Is currently participating and receiving investigational therapy or using an investigational device, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the investigational product, whichever is longer, prior to the first dose of PH009-1.

3. Is expected to require any other form of anti-tumor therapy while on study.

4. Unresolved toxicity greater than CTCAE v5.0 Grade 1 from prior anti-tumor therapy prior to the first dose.

5. Medical history of severe eye disease or skin disease without recovery to CTCAE v5.0 Grade 0 or 1 prior to the first dose.

6. Any of the following cardiovascular diseases within the last 6 months: include but not limited to QTc interval ≥ 470 msec.

7. Medical history of ILD.

8. Subjects with gastrointestinal disorders that may affect oral administration or interfere with the absorption of PH009-1, or severe gastrointestinal disease within 4 weeks prior to the first dose of PH009-1 and did not recover to ≤ CTCAE v5.0 Grade 2.

9. Major surgery or significant traumatic injury occurring within 4 weeks prior to the first dose of PH009-1 or anticipation of need for a major surgery during the study.

10. Has any bleeding tendency or coagulopathy within 6 months prior to the first dose of PH009-1.