This study is designed to evaluate safety and antitumor activity of DZD6008 combination therapy in patients with advanced Non-Small Cell Lung Cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) mutations.

Inclusion Criteria:

1. Signed informed consent.
2. Age ≥18 years old.
3. Locally advanced or metastatic non-squamous non-small cell lung cancer by histopathology or cytology, not suitable for other radical treatment.
4. Documentation of EGFR sensitizing mutation confirmed by local laboratory.
5. Provide sufficient tumor tissue samples and plasma samples for retrospective analysis of EGFR mutations by central laboratory.
6. Failure of prior 3 generations EGFR TKI.
7. ECOG status score 0-1, life expectancy ≥12 weeks.
8. No central nervous system symptoms during screening, no need for corticosteroids or dehydration diuretic treatment for at least 4 weeks before the first dosing. If the patient with brain metastasis has received radiotherapy or surgery, there is a washout period of ≥2 weeks before the first use of DZD6008 and ensure that the AE related to radiotherapy or surgery has recovered to ≤ 1 grade.
9. Presence of measurable lesions defined by RECIST 1.1.
10. Sufficient bone marrow or other organ reserve before first dosing.

Exclusion criteria

1. Histology mixed with small cell lung cancer (SCLC) or with SCLC transformation.

2. Received the following treatments or had the following lifestyle habits, etc.:

   • Received immunotherapy or other antibody treatments (including EGFR-targeted antibodies, bispecific antibodies or antibody-drug conjugates, etc.) within 4 weeks before the first study drug administration.
   • Received any cytotoxic chemotherapy, study drugs or other anti-cancer drugs (excluding macromolecule drugs) within 14 days before the first study drug administration.
   • Received limited-range radiotherapy to relieve the disease within 7 days before the first study drug administration, or received more than 30% of the bone marrow radiotherapy or received wide-range radiotherapy within 28 days before the first medication.
   • 2 weeks (for CYP3A4 inhibitors) or 3 weeks (for CYP3A4 inducers) before the first study drug administration, are taking or cannot stop taking known cytochrome P450 (CYP) 3A4 strong inhibitors or inducers (including herbal supplements, such as St. John's wort).
   • 2 weeks before the first study drug administration, are taking or cannot stop taking known CYP3A4 sensitive substrate drugs (with a narrow therapeutic window).
   • Taking or being unable to stop taking drugs known to be proton pump inhibitors within 1 week before the first study drug administration.
   • Major invasive surgery has been performed within 4 weeks before the first study drug administration or is planned during treatment.

3. Presence of AEs of ≥1 grade (except any degree of alopecia) caused by previous treatment (such as adjuvant chemotherapy, radiotherapy).

4. Tumor-related spinal cord compression or meningeal metastasis.

5. History of malignant tumor within 2 years (except for basal cell carcinoma of the skin or cervical cancer in situ that has been adequately treated; other tumors that have been tumor-free for more than 2 years and are expected to survive for more than 2 years, which needs to be discussed with Dizal clinical research physicians).

6. Presence of severe or uncontrollable systemic diseases, including poorly controlled hypertension, bleeding diseases.

7. Presence of persistent or active infections, including but not limited to hepatitis B, hepatitis C and human immunodeficiency virus infection (HIV).

8. Any of the following heart-related diseases or abnormalities:

   • QT interval (QTc) >470 msec after calibration of 12-lead ECG at rest during the screening period.
   • Any serious abnormalities of heart rate, conduction or pattern shown on the ECG at rest, such as complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec.
   • Any disease or condition that can cause QTcF prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or family members with a history of sudden death under the age of 40.
   • Severe cardiovascular diseases such as myocardial infarction, unstable angina or congestive heart failure, cerebrovascular accident (such as history of stroke or intracranial hemorrhage) within 6 months before the first dose.
   • History of deep vein thrombosis or pulmonary embolism within 4 weeks before the first dose (excluding non-obstructive catheter-related thrombosis).

9. Patient history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid hormone treatment, or any clinically active ILD, immunotherapy-related pneumonitis.

10. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing medication, or previous intestinal resection that prevents adequate absorption of study medication.

11. Live vaccine within 4 weeks before the first dose.