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Assessing an Oral EGFR Inhibitor, DZD9008 in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03974022
Recruitment Status : Recruiting
First Posted : June 4, 2019
Last Update Posted : January 12, 2023
Sponsor:
Information provided by (Responsible Party):
Dizal Pharmaceuticals

Study Description
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Brief Summary:
This study will treat patients with advanced NSCLC with EGFR or HER2 mutation who have progressed following prior therapy. This is the first time this drug is tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment. It will also measure the levels of drug in the body and preliminarily assess its anti-cancer activity as monotherapy.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: DZD9008 Phase 1 Phase 2

Detailed Description:
A Phase I/II, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of DZD9008 in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with EGFR or HER2 mutation. This study includes dose escalation, dose expansion, food effect (Part A) and dose extension (Part B).
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 336 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of DZD9008 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) With EGFR or HER2 Mutation
Actual Study Start Date : July 9, 2019
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part A Dose escalation Drug: DZD9008
Daily dose of DZD9008
Experimental: Part A Dose expansion cohort 1 Drug: DZD9008
Daily dose of DZD9008
Experimental: Part A Dose expansion cohort 2 Drug: DZD9008
Daily dose of DZD9008
Experimental: Part A Dose expansion cohort 3
Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy
 Drug: DZD9008
Daily dose of DZD9008
Experimental: Part A Dose expansion cohort 4 (Ongoing)
Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy
 Drug: DZD9008
Daily dose of DZD9008
Experimental: Part A Dose expansion cohort 5 (Ongoing)
Patients with EGFR Exon20ins, treatment naïve
 Drug: DZD9008
Daily dose of DZD9008
Experimental: Part A Dose expansion cohort 6 Drug: DZD9008
Daily dose of DZD9008
Experimental: Part B Dose extension (Ongoing)
Patients with EGFR Exon20ins should have received at least 1 line, but no more than 3 lines of systemic therapy for metastatic/locally advanced disease.
 Drug: DZD9008
Daily dose of DZD9008


Outcome Measures
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Primary Outcome Measures :
  1. Part A: Safety and tolerability of DZD9008. [ Time Frame: 28 days after the first multiple dose ]
    To investigate the safety and tolerability of DZD9008 when given orally to patients with advanced NSCLC with EGFR or HER2 mutations; To establish Maximum Tolerated Dose (MTD) (if possible) and Recommended Phase 2 Dose (PR2D) of DZD9008 when given orally in patients with advanced NSCLC with EGFR or HER2 mutations.

  2. Part B: Objective Response Rate (ORR) according to RECIST 1.1. [ Time Frame: through the study completion, an average of around 1 year ]
    To evaluate anti-tumor activity of DZD9008 in advanced NSCLC patients with EGFR Exon20 insertion, HER2 Exon20 insertion or EGFR uncommon mutations at defined dose(s) (Part B)


Secondary Outcome Measures :
  1. Plasma DZD9008 concentration [ Time Frame: Through cycle 3 day 1 (8 days for Cycle 0, 28 days for Cycle 1, then 21 days for each subsequent cycle) ]
    To characterize the pharmacokinetics (PK) of DZD9008 following a single oral dosing and at steady state after multiple oral dosing, and renal excretion of DZD9008


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged at least 18 years old, be able to provide a signed and dated, written informed consent.
  2. With documented histological or cytological confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations.
  3. (ECOG) performance status 0-1.
  4. Predicted life expectancy ≥ 12 weeks
  5. Patient must have measurable disease according to RECIST 1.1.
  6. Patients with brain metastasis (BM) can be enrolled under the condition that BM is stable, neurologically asymptomatic and does not require corticosteroid treatment.

  7. Adequate organ system function.

    Part A Dose expansion:

  8. Dose expansion cohort 5: NSCLC patients with EGFR Exon20ins, who have not received prior systemic therapy (treatment naïve).

    Part B dose extension:

  9. Patients must have histologically or cytologically confirmed locally advanced or metastatic NSCLC with documented EGFR Exon20ins mutation in tumor tissue from a local CLIA-certified laboratory (or equivalent) or Sponsor designated central laboratory prior to the study entry.
  10. Patients should have received at least 1 line, but no more than 3 lines of systemic therapy for metastatic/locally advanced disease.

Exclusion Criteria:

  1. For part B: Patients who have received prior treatment with Poziotinib or TAK788 or other EGFR/HER2 exon20 insertion inhibitors should be excluded. Prior treatment with currently approved EGFR TKIs for sensitizing or T790M resistance mutations, such as gefitinib, erlotinib, osimertinib, afatinib and dacomitinb, are allowed.
  2. Treatment with EGFR or HER2 antibodies, major surgery (excluding placement of vascular access), or onco-immunotherapy (e.g. immune checkpoint inhibitors PD-1, PD-L1, CTLA-4) within 4 weeks before screening.
  3. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before screening.
  4. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose or with a wide field of radiation which must be completed within 4 weeks before screening.
  5. Receiving (or unable to stop using) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A within 2-3 weeks before screening.
  6. Grapefruit, grapefruit juice, and orange marmalade (made with Seville oranges) within 1 week before screening.
  7. 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.
  8. Spinal cord compression or leptomeningeal metastasis.
  9. 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).
  10. Any of the following cardiac criteria: (1) Mean resting corrected QT interval (QTcF) > 470 msec obtained from 3 electrocardiograms (ECGs); (2) 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. (3) 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
  11. 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
  12. 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
  13. History of hypersensitivity to active or inactive excipients of DZD9008 or drugs with a similar chemical structure or class to DZD9008
  14. Women who are pregnant or breast feeding
  15. Involvement in the planning and conduct of the study.
  16. 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03974022


Contacts
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Contact: Li Zheng, M.D & Ph. D 86-21-61097899 li.zheng@dizalpharma.com
Contact: Pamela Yang, M.D & Ph. D 86-21-61097866 pamela.yang@dizalpharma.com

Locations
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Sponsors and Collaborators
Dizal Pharmaceuticals
Investigators
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Principal Investigator: Pasi Antero Janne, M.D & Ph. D Dana-Farber Cancer Institute
More Information
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Responsible Party: Dizal Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03974022    
Other Study ID Numbers: DZ2019E0001
First Posted: June 4, 2019    Key Record Dates
Last Update Posted: January 12, 2023
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dizal Pharmaceuticals:
Non-Small Cell Lung Cancer
EGFR
HER2
mutation
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms