Assessing an Oral EGFR Inhibitor, DZD6008 in Patients Who Have Advanced NSCLC With EGFR Mutations (TIAN-SHAN2)

Inclusion Criteria:

1. Patients must be able to provide documented informed consent.

2. Aged ≥ 18 years.

3. Histologically or cytologically confirmed diagnosis of NSCLC, locally advanced ormetastatic, not suitable for curative therapy.

4. Documentation of EGFR mutation from a local CLIA-certified laboratory (orequivalent). Part A: EGFR sensitizing mutation (Exon19del and/or L858R). Part B:EGFR sensitizing mutation (Exon19del and/or L858R) and C797X mutation.

5. Provide adequate amount of pretreatment tumor samples collected after diseaseprogression on the last EGFR TKI treatment.

6. Failed (progressed or are intolerant) at least 1 prior EGFR TKI regimen. Patientsenrolled in Part A will be required to have progressed or become intolerant afteradequate treatment with at least one-line EGFR TKI and platinum-containingchemotherapy.

7. ECOG 0 or 1 with predicted life expectancy ≥ 12 weeks.

8. Patients with brain metastases must have a stable BM status.

9. Measurable disease per RECIST 1.1.

10. Adequate hematopoietic and other organ system functions.

11. Male Patients with female partners of childbearing potential should use barriercontraceptives and refrain from donating sperm during their participation in thisstudy and for 3 months following the last dose of the study drug.

Exclusion Criteria:

1. Carry any other known EGFR alterations, including but not limited to uncommon EGFRmutations (G719X, S768I, L861Q, exon 20 insertions, etc.)(Part B).

2. NSCLC with mixed small cell lung cancer (SCLC) or NSCLC with histologic SCLCtransformation.

3. Prior treatment with any of the following:1)Immunotherapy or other antibody therapywithin 4 weeks prior to the first administration;2)Any cytotoxic chemotherapy,investigational drugs or other anticancer drugs from a previous treatment regimen orclinical study within 14 days prior to the first administration;3)Radiotherapy witha limited field of radiation for palliation within 7 days of the first dose,radiation to more than 30% of the bone marrow or with a wide field of radiationwithin 28 days before screening;4)Currently receiving or unable to stop drug orherbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP)3A4. A washout period of at least 2 weeks for strong inhibitors and 3 weeks forstrong inducers is required prior to the first study drug administration.5)currentlyreceiving or unable to stop drugs known to be CYP3A4 sensitive substrate with anarrow therapeutic index. A washout period of at least 14 days is required prior tothe first study drug administration;6)currently receiving or unable to stop drugsknown to be proton pump inhibitors. A washout period of at least 7 days is requiredprior to the first study drug administration;7)Major surgery within 4 weeks of thefirst administration of DZD6008 or anticipated during the study period.

4. Any unresolved toxicities from prior anti-cancer therapy greater than CTCAE Grade 1.

5. Spinal cord compression or leptomeningeal metastasis.

6. Patients with any other malignancy within 2 years of the first administration ofstudy drug.

7. Any evidence of severe or uncontrolled systemic diseases, including uncontrolledhypertension and active bleeding diatheses as judged by investigator.

8. Patients with active infection including but not limited to HBV, HCV, HIV and activeinfection of COVID-19.

9. Resting QTcF > 470 msec; Any clinically significant abnormalities in rhythm,conduction or morphology of resting ECG;Any factors that increase the risk of QTcprolongation.

10. Past medical history of ILD or active ILD.

11. Diseases which would preclude adequate absorption of DZD6008.

12. Received a live vaccine within 2 weeks before the first administration of DZD6008.

13. Women who are pregnant or breastfeeding.

14. Hypersensitivity to active or inactive excipients of DZD6008.

15. Involvement in the planning and conduct of the study.

16. Judgment by the investigator that the patients is unlikely to comply with studyprocedures