DZD9008 in Pretreated Lung Cancer Patients With EGFR Exon20 Insertion Mutation

Non-Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05712902
• Other study ID #: DZ2020E0001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 19, 2021
• Est. completion date: May 6, 2024

Study information

• Verified date: January 2023
• Source: Dizal Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II, single-arm, multi-center clinical study to evaluate the anti-tumor efficacy, safety, tolerability and pharmacokinetics of DZD9008 in participants with locally advanced or metastatic NSCLC carrying EGFR exon 20 insertion mutations whose disease has progressed on prior platinum-based chemotherapy

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 104
• Est. completion date: May 6, 2024
• Est. primary completion date: October 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 DZD9008 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 DZD9008.

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 DZD9008, 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 DZD9008.

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 DZD9008.

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 DZD9008.

12. Women who are pregnant or breast feeding.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• DZD9008
Daily dose of DZD9008

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Beijing Chest Hospital,Capital Medical University	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	Jilin Cancer Hospital	Chang chun
China	Hunan Cancer Hospital(The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University	Changsha
China	West China Hospital of Sichuan University	Chengdu
China	Army Medical Center of PLA	Chongqing
China	Chongqing University Cancer Hospital(Chongqing Cancer Hospital)	Chongqing
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	The First Affiliated Hospital, Sun Yat-sen University	Guangzhou
China	Hainan General Hospital	Haikou
China	The First Affiliated Hospital Zhejiang University School of Medicine	Hangzhou
China	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou
China	Zhejiang Cancer Hospital (Cancer Hospital of the University of Chinese Academy of Sciences)	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	The Second Hospital of Anhui Medical University	Hefei
China	The Affiliated Hospital of Inner Mongolia Medical University	Hohhot
China	Jinan Central Hospital (Central Hospital Affiliated to Shandong First Medical University)	Jinan
China	Yunnan Cancer Hospital	Kunming
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	The Second Affiliated Hospital of Nanchang University	Nanchang
China	Fudan University Shanghai Cancer Center	Shanghai
China	The First Hospital of China Medical University	Shenyang
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang
China	The First Affiliated Hospital of Soochow University	Suzhou
China	Shanxi Provincial Cancer Hospital	Taiyuan
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
China	The Affiliated Cancer Hospital of Xinjiang Medical University	Ürümqi
China	Hubei Cancer Hospital	Wuhan
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an
China	Affiliated Cancer Hospital of Zhengzhou University(Henan Cancer Hospital)	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Dizal Pharmaceuticals

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) according to RECIST 1.1 by an Independent Review Committee (IRC)		From first dosing until disease progression or intolerable adverse events