Assessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1)

Inclusion Criteria:

1. Aged at least 18 years old, be able to provide a signed and dated, written informedconsent.

2. With documented histological or cytological confirmed locally advanced or metastaticNSCLC with EGFR or HER2 mutations.

3. (ECOG) performance status 0-1.

4. Predicted life expectancy ≥ 12 weeks

5. Patient must have measurable disease according to RECIST 1.1.

6. Patients with brain metastasis (BM) can be enrolled under the condition that BM ispreviously treated and stable, neurologically asymptomatic and does not requirecorticosteroid treatment.

7. Adequate organ system function.

8. Part A Dose expansion: Dose expansion cohort 5: NSCLC patients with EGFR Exon20ins,who have not received prior systemic therapy (treatment naïve). Part B Dose extension:

9. Patients must have histologically or cytologically confirmed locally advanced ormetastatic NSCLC with documented EGFR Exon20ins mutation in tumor tissue from alocal CLIA-certified laboratory (or equivalent) or Sponsor designated centrallaboratory prior to the study entry.

10. Patients should have received at least 1 line, but no more than 3 lines of systemictherapy for metastatic/locally advanced disease.

Exclusion Criteria:

1. For part B: Patients who have received prior treatment with Poziotinib or TAK788 orother EGFR/HER2 exon20 insertion inhibitors should be excluded. Prior treatment withcurrently approved EGFR TKIs for sensitizing or T790M resistance mutations, such asgefitinib, erlotinib, osimertinib, afatinib and dacomitinib, are allowed unless thepatient had an objective response and subsequent progression assessed by theinvestigator.

2. Treatment with EGFR or HER2 antibodies, major surgery (excluding placement ofvascular access), or onco-immunotherapy (e.g. immune checkpoint inhibitors PD-1,PD-L1, CTLA-4) within 4 weeks before the first administration of Sunvozertinib.

3. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from aprevious treatment regimen or clinical study within 14 days before the firstadministration.

4. Radiotherapy with a limited field of radiation for palliation within 1 week of thefirst dose or with a wide field of radiation which must be completed within 4 weeksbefore the first administration.

5. Receiving (or unable to stop using) medications or herbal supplements known to bepotent inhibitors or inducers of CYP3A within 1-2 weeks before the firstadministration.

6. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the timeof starting Sunvozertinib with the exception of alopecia and grade 2 priorplatinum-therapy related neuropathy.

7. Spinal cord compression or leptomeningeal metastasis.

8. As judged by the investigator, any evidence of severe or uncontrolled systemicdiseases, which would jeopardize compliance with the protocol, or active infectionincluding hepatitis B, hepatitis C, human immunodeficiency virus (HIV) and COVID-19 (per local practice).

9. Any of the following cardiac criteria: (1) Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs); (2) Any clinically significantabnormalities in rhythm, conduction or morphology of resting ECG, e.g., completeleft bundle branch block, third degree heart block, and second-degree heart block,PR interval > 250 msec. (3) Any factors that increase the risk of QTF prolongation,such as heart failure, hypokalemia, congenital long QT syndrome, family history oflong QT syndrome or unexplained sudden death under 40 years of age in first degreerelatives or any concomitant medication known to prolong the QT interval; (4) Priorhistory of atrial fibrillation within 6 months of first administration ofSunvozertinib, except prior drug treatment related and recovered.

10. Past medical history of interstitial lung disease, drug-induced interstitial lungdisease, radiation pneumonitis which required steroid treatment, or any evidence ofclinically active interstitial lung disease.

11. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability toswallow the formulated product or previous significant bowel resection that wouldpreclude adequate absorption of Sunvozertinib.

12. History of hypersensitivity to active or inactive excipients of Sunvozertinib ordrugs with a similar chemical structure or class to Sunvozertinib.

13. Women who are pregnant or breast feeding.

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

15. Judgment by the investigator that the patient should not participate in the study ifthe patient is unlikely to comply with study procedures, restrictions andrequirements.