Sunvozertinib (DZD9008) in Pretreated Lung Cancer Patients with EGFR Exon20 Insertion Mutation (WU-KONG6)

A Phase II, Single Arm, Multicenter Study to Evaluate Anti-tumor Activity, Safety, Tolerability and Pharmacokinetics of DZD9008 in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with EGFR Exon 20 Insertion Mutation

This is a Phase II, single-arm, multi-center clinical study to evaluate the anti-tumor efficacy, safety, tolerability and pharmacokinetics of Sunvozertinib in participants with locally advanced or metastatic NSCLC carrying EGFR exon 20 insertion mutations whose disease has progressed on prior platinum-based chemotherapy

Inclusion Criteria:

1. Patients must be able to understand the nature of the trial and provide a signed and dated, written informed consent form.
2. Aged at least 18 years old.
3. Histological or cytological confirmed locally advanced or metastatic NSCLC
4. Tumor tissue EGFR exon 20 insertion mutations confirmed by qualified local laboratories or sponsor-designated central laboratories.
5. Participants must exhibit Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 at ICF signature with no deterioration over the past 2 weeks.
6. Predicted life expectancy ≥ 12 weeks.
7. Patient must have measurable disease according to RECIST 1.1.
8. Patients with brain metastasis (BM) can only be enrolled under the condition that BM is previously treated and stable.
9. Adequate organ system functions.
10. Patients should receive at least one line but no more than three lines of prior systemic therapy (at least one line must contain platinum-based therapy).

Exclusion Criteria:

1. Prior malignancy within 2 years requires active treatment, except for adequately treated basal cell skin carcinoma, in situ cervical carcinoma, or other cancer types (to be discussed with Dizal's Study Physician) who has been disease free for > 2 years with life expectancy >2 years.

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

3. Spinal cord compression or leptomeningeal metastasis.

4. History of stroke or intracranial hemorrhage within 6 months before first administration of Sunvozertinib.

5. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses.

6. Active infection including hepatitis B, hepatitis C, human immunodeficiency virus (HIV) and COVID-19.

7. Any of the following cardiac criteria:

   • Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs).
   • Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, third degree heart block, and second-degree heart block, PR interval > 250 msec.
   • Any factors that increase the risk of QTc prolongation, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval .
   • Prior history of atrial fibrillation within 6 months of first administration of Sunvozertinib, except prior drug treatment related and recovered.

8. Participants with hemorrhagic diseases such as von Willebrand disease.

9. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease or immunotherapy induced immune pneumonia.

10. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Sunvozertinib.

11. Prior/concomitant therapy

    1. Patients who have received prior Poziotinib, TAK-788, CLN-081 or BDTX-189, furmonertinib or any other EGFR/HER2 exon20ins small molecule inhibitors treatment should be excluded.
    2. Other EGFR TKIs, such as gefitinib, erlotinib, osimertinib, afatinib, dacomitinb are not considered EGFR or HER2 Exon20ins small molecule inhibitors, and thus prior treatment with these drugs is allowed unless the patient had an objective response and subsequent progression as assessed by the investigator or treating physician during treatment with that prior TKI.
    3. Treatment with antibodies within 4 weeks before first administration of Sunvozertinib.
    4. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before first administration of Sunvozertinib.

12. Women who are pregnant or breast feeding.