Combination treatment for advanced lung cancer with specific mutations

A Phase II, Single-Arm Study Evaluating the 1st Line Efficacy and Safety of Sunvozertinib Plus Anlotinib in EGFR-Sensitive Mutations Combined With Co-Mutations Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (WUKONG-32)

This study is testing a new combination of two drugs for people with advanced lung cancer who have specific genetic mutations to see if it helps them live longer without their cancer getting worse.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hunan Province Tumor Hospital (other)
• Drugs / interventions: sunvozertinib, anlotinib, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Changsha, Hunan)
• Trial ID: NCT06348927 on ClinicalTrials.gov

What this trial studies

This phase II clinical study evaluates the effectiveness of sunvozertinib combined with anlotinib in patients with advanced non-small cell lung cancer (NSCLC) who have EGFR-sensitive mutations and co-mutations. The study will enroll approximately 52 treatment-naive patients and administer sunvozertinib daily alongside anlotinib for a specified regimen until disease progression or intolerable side effects occur. The primary goal is to assess progression-free survival, while secondary goals include overall response rate, disease control rate, overall survival, and safety. Recruitment is expected to begin in mainland China in April 2024, with the study concluding in April 2027.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed EGFR-sensitive mutations and co-mutations in locally advanced or metastatic NSCLC who have not received prior systemic treatment.

Not a fit: Patients who have previously undergone systemic therapy for their advanced lung cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced NSCLC harboring specific genetic mutations.

How similar studies have performed: While this approach is novel in its specific combination, similar studies targeting EGFR mutations in NSCLC have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
2. Age ≥ 18 years.
3. Histopathology or cytology confirmed and recorded local progression or metastatic non-small cell lung cancer without systemic treatment.
4. EGFR-sensitive mutations confirmed by an accredited local laboratory, including exon 19 deletions, exon 21 L858R point mutations, and T790M mutations, combined with co-mutations, including but not limited to TP53, PIK3CA, catenin beta-1 (CTNB1), and retinoblastoma (RB1).
5. ECOG 0 - 1.
6. Predicted survival ≥ 12 weeks.
7. Adequate bone marrow hematopoiesis and organ function
8. Presence of measurable lesions according to RECIST 1.1.
9. Subjects with stable brain metastases may be included in the study.

Exclusion Criteria:

1. Prior systemic therapy for locally advanced or metastatic disease.
2. Subjects who have received any of the following treatments must be excluded:

   * Treatment with molecules such as EGFR, VEGFR antibodies within 4 weeks prior to the first dose of study drug.
   * Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
   * Ongoing (or inability to discontinue) possibly potent CYP1A2, CYP3A inhibitor (1 week), or inducer (2 weeks) drug therapy or herbal supplements within 1-2 weeks prior to the first dose.
3. Presence of spinal cord compression or meningeal metastasis.
4. History of other malignant tumors within 2 years.
5. Adverse events (except alopecia of any degree) of CTCAE \> grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
6. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
7. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
8. Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
9. Heart-related diseases or abnormalities
10. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
11. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
12. Live vaccine was given 2 weeks before the first medication.
13. Women who are breastfeeding or pregnant.
14. Hypersensitivity to the test drug and the ingredients.
15. Other conditions assessed by the investigator to be unsuitable for participation in the study.

Where this trial is running

Changsha, Hunan

• Hunan Cancer Hospital — Changsha, Hunan, China (RECRUITING)

Study contacts

• Principal investigator: Yongchang Zhang — Hunan Cancer Hospital
• Study coordinator: Yongchang Zhang

Conditions: Non-Small Cell Lung Cancer, sunvozertinib, anlotinib, EGFR mutations