Evaluating DZD9008 for advanced lung cancer with specific mutations

DZD9008 in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With EGFR Mutations: Cohort Study

This study is testing a new oral medication called DZD9008 to see if it helps people with advanced lung cancer who have certain genetic mutations and have either already tried other treatments or are starting treatment for the first time.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT05559645 on ClinicalTrials.gov

What this trial studies

This study assesses the effectiveness, safety, and tolerability of the oral EGFR inhibitor DZD9008 in patients with advanced non-small cell lung cancer (NSCLC) who have specific EGFR mutations. It includes patients who have progressed after standard therapy as well as treatment-naive patients with certain mutations. The study aims to determine how well DZD9008 works in these populations, focusing on those with locally advanced or metastatic disease. Participants will be monitored for measurable disease outcomes according to established criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced NSCLC harboring EGFR mutations who have either progressed after standard therapy or are treatment-naive.

Not a fit: Patients without documented EGFR mutations or those with uncontrolled brain metastases may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced NSCLC who have specific EGFR mutations.

How similar studies have performed: Other studies have shown promising results with EGFR inhibitors in similar patient populations, suggesting potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. To provide a signed and dated, written informed consent.
2. Aged ≥ 18 years old
3. Histologically or cytologically confirmed locally advanced or metastatic NSCLC with documented EGFR mutations from a local laboratory
4. ECOG performance status 0-1.
5. Predicted life expectancy ≥ 12 weeks
6. Patient must have measurable disease according to RECIST 1.1.
7. Patient who has progressed or intolerant to standard therapy (except treatment naïve patients in Cohort 4 and Cohort 7: with EGFR Exon20ins; and in Cohort 5 with EGFR sensitizing mutation).
8. Patients with brain metastasis (BM) can be enrolled under the condition that BM is stable, neurologically asymptomatic and does not require corticosteroid treatment.
9. Adequate organ system function.

   * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
   * Platelets ≥ 100 x 10\^9/L
   * Hemoglobin ≥ 9 g/dL
   * Total bilirubin ≤ 1.5 x ULN if no liver metastases or ≤ 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
   * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN if no liver metastases or ≤ 5 x ULN with liver metastases
   * Creatinine ≤ 1.5 x ULN, concurrent with calculated or measured creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault method or ≥ 50 mL/min in 24 hours
   * International normalized ratio (INR) ≤ 1.5 x ULN and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN;
   * Serum amylase ≤ 1.5 x ULN and serum lipase ≤ 1.5 x ULN

Exclusion criteria:

1. Known history of bleeding diathesis.
2. Prior malignancy within 2 years requires active treatment.
3. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of first administration.
4. History of stroke or intracranial haemorrhage within 6 months before the first administration.
5. Spinal cord compression or leptomeningeal metastasis.
6. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
7. Any of the following cardiac criteria:

   * Mean resting corrected QT interval (QTcF) \> 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 QTcF 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 DZD9008, except prior drug treatment related and recovered.
8. 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.
9. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of DZD9008.
10. History of hypersensitivity to active or inactive excipients of DZD9008 or drugs with a similar chemical structure or class to DZD9008.
11. Women who are pregnant or breast feeding.
12. Involvement in the planning and conduct of the study.
13. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

Where this trial is running

Beijing, Beijing Municipality

• Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Yan Xu, Dr.

Conditions Non Small Cell Lung Cancer