Assessing an Oral EGFR Inhibitor, DZD9008 in Patients With Advanced Non-small Cell Lung Cancer(NSCLC) With EGFR Mutations (WU-KONG15) (WU-KONG15)

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

This study is a single center cohort study to access the anti-tumor efficacy, safety and tolerability of DZD9008 in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) sensitizing mutations and EGFR uncommon mutations who have progressed following standard TKI therapy, and in treatment naive patients with NSCLC harboring EGFR Exon20 insertion mutation.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: DZD9008

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yan Xu, Dr.; Phone Number: 010-69155039; Email: maraxu@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 patient with EGFR Exon20ins in Cohort 4).
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."

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1: EGFR sensitizing mutations, T790M neg	Drug: DZD9008; Daily dosing of DZD9008
EXPERIMENTAL: Cohort 2: EGFR sensitizing mutations	Drug: DZD9008; Daily dosing of DZD9008
EXPERIMENTAL: Cohort 3: EGFR uncommon mutations	Drug: DZD9008; Daily dosing of DZD9008
EXPERIMENTAL: Cohort 4: EGFR Exon20ins	Drug: DZD9008; Daily dosing of DZD9008

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	To assess anti-tumor activity of DZD9008 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DoR)	To assess anti-tumor activity of DZD9008 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator	through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control rate (DCR)	To assess anti-tumor activity of DZD9008 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator	through study completion, an average of 1 year
Objective Response Rate (ORR)	To assess anti-tumor activity of DZD9008 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator	through study completion, an average of 1 year
Overall survival (OS)	To assess anti-tumor activity of DZD9008 according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator	through study completion, an average of 1 year
Number of participants with adverse events (AEs) according to CTCAE 5.0	To assess safety and tolerability of DZD9008 when given orally to patients with advanced NSCLC	From first dose until 28 days after the last dose
Number of participants with clinically significant laboratory assessment abnormalities	To assess safety and tolerability of DZD9008 when given orally to patients with advanced NSCLC	From first dose until 28 days after the last dose
Number of participants with clinically significant abnormal vital signs	To assess safety and tolerability of DZD9008 when given orally to patients with advanced NSCLC	From first dose until 28 days after the last dose
Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities	To assess safety and tolerability of DZD9008 when given orally to patients with advanced NSCLC	From first dose until 28 days after the last dose

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Dizal (Jiangsu) Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 18, 2021
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): June 30, 2024

Study Registration Dates

• First Submitted: July 30, 2022
• First Submitted That Met QC Criteria: September 24, 2022
• First Posted (ACTUAL): September 29, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 24, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: DZ2021E0006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No