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

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 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.

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 336
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Li Zheng, M.D & Ph. D; Phone Number: 86-21-61097899; Email: li.zheng@dizalpharma.com
• Study Contact Backup: Name: Pamela Yang, M.D & Ph. D; Phone Number: 86-21-61097866; Email: pamela.yang@dizalpharma.com

Study Locations

• Australia
  • Blacktown, Australia
    • Recruiting
    • Blacktown Hospital
    • Contact: Gao
  • Camperdown, Australia
    • Recruiting
    • Chris O'Brien Lifehouse
    • Contact: Boyer
  • Heidelberg, Australia
    • Recruiting
    • Austin Hospital
    • Contact: Mitchell
  • Kogarah, Australia
    • Recruiting
    • St George Hospital
    • Contact: Lee
  • North Melbourne, Australia
    • Recruiting
    • Peter MacCallum Cancer Centre - East Melbourne
    • Contact: John
  • Perth, Australia
    • Recruiting
    • Linear Cancer Trials
    • Contact: Michael Millward
  • Wollongong, Australia
    • Recruiting
    • Southern Medical Day Care Centre
    • Contact: Brungs
• France
  • Dijon, France
    • Recruiting
    • Centre Georges François Leclerc
    • Contact: Ghiringhelli
  • Marseille, France
    • Recruiting
    • Hôpital de La Timone AP-Hm
    • Contact: Greillier
  • Montpellier, France
    • Recruiting
    • CHU de Montpellier Hôpital Arnaud de Villeneuve
    • Contact: Pujol
  • Paris, France
    • Recruiting
    • APHP-Hôpital Bichat - Claude Bernard
    • Contact: Zalcman
  • Poitiers, France
    • Recruiting
    • CHU de Poitiers
    • Contact: Isambert
  • Saint-Herblain, France
    • Recruiting
    • Institut de Cancérologie de l'Ouest
    • Contact: Doucet
  • Villejuif, France
    • Recruiting
    • Institut Gustave Roussy
    • Contact: Planchard
• Italy
  • Catania, Italy
    • Not yet recruiting
    • Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"
    • Contact: Soto Parra
  • Firenze, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria Careggi
    • Contact: Antonuzzo
  • Meldola, Italy
    • Recruiting
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST IRCCS
    • Contact: Delmonte
  • Milano, Italy
    • Recruiting
    • Istituto Europeo Di Oncologia
    • Contact: Curigliano
  • Ravenna, Italy
    • Recruiting
    • AUSL Romagna - Ospedale S.M delle Croci
    • Contact: D'Arcangelo
  • Reggio Emilia, Italy
    • Recruiting
    • Arcispedale Santa Maria Nuova
    • Contact: Zanelli
  • Roma, Italy
    • Recruiting
    • Istituti Fisioterapici Ospitalieri
    • Contact: Di Noia
• Japan
  • Matsuyama-shi, Japan
    • Completed
    • National Hospital Organization Shikoku Cancer Center
  • Nagoya-Shi, Japan
    • Completed
    • Aichi Cancer Center Hospital
  • Niigata-Shi, Japan
    • Completed
    • Niigata University Medical & Dental Hospital
  • Okayama-Shi, Japan
    • Completed
    • Okayama University Hospital
  • Tokushima-Shi, Japan
    • Completed
    • Tokushima University Hospital
  • Tokyo, Japan
    • Completed
    • Tokyo Shinagawa Hospital
• Korea, Republic of
  • Cheonju, Korea, Republic of
    • Recruiting
    • Chungbuk National University Hospital
    • Contact: Lee
  • Goyang, Korea, Republic of
    • Recruiting
    • National Cancer Center
    • Contact: Han
  • Seongnam, Korea, Republic of
    • Recruiting
    • Seoul National University Bundang Hospital
    • Contact: Kim
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center
    • Contact: Lee
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Kim
  • Suwon, Korea, Republic of
    • Recruiting
    • The Catholic University of Korea, St. Vincent's Hospital
    • Contact: Shim
• Malaysia
  • Johor Bahru, Malaysia
    • Not yet recruiting
    • Hospital Sultan Ismail
    • Contact: Lim
  • Kuala Lumpur, Malaysia
    • Not yet recruiting
    • University Malaya Medical Centre
    • Contact: Pang
  • Kuala Lumpur, Malaysia
    • Not yet recruiting
    • Hospital Kuala Lumpur
    • Contact: Thiagarajan
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Felip
  • Barcelona, Spain
    • Recruiting
    • ICO (Institut Catala d'Oncologia) Badalona - Hospital Germans Trias i Pujol
    • Contact: Carcereny
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Contact: Paz-Ares Rodriguez
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: de Castro Carpeno
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ramon y Cajal
    • Contact: Garrido
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
    • Contact: Manuel Domine Gomez
  • Madrid, Spain
    • Recruiting
    • Centro Integral Oncológico Clara Campal (CIOCC)
    • Contact: de Miguel-Luken
  • Malaga, Spain
    • Recruiting
    • Hospital Regional Universitario de Malaga
    • Contact: Cobo-Dols
  • Sevilla, Spain
    • Recruiting
    • Hospital Universitario Virgen Macarena
    • Contact: Vicente Baz
• Taiwan
  • Liuying, Taiwan
    • Recruiting
    • Chi Mei Hospital, Liouying
    • Contact: Huang
  • Taichung, Taiwan
    • Recruiting
    • Taichung Veterans General Hospital
    • Contact: Yang
  • Tainan, Taiwan
    • Recruiting
    • National Cheng Kung University Hospital
    • Contact: Su
  • Taipei, Taiwan
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Chiu
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Yang
  • Taipei, Taiwan
    • Recruiting
    • Wan Fang Hospital
    • Contact: Chang
  • Taoyuan, Taiwan
    • Recruiting
    • Chang Gung Memorial Hospital
    • Contact: Hsu
• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California, San Diego (UCSD) - Moores Cancer Center
      • Contact: Bazhenova, MD
    • Orange, California, United States, 92868
      • Recruiting
      • University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
      • Contact: Nagasaka, MD
    • Whittier, California, United States, 90603-2137
      • Recruiting
      • Innovative Clinical Research Institute, LLC
      • Contact: Miel, MD
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Hospital - Anschutz Cancer Pavilion
      • Contact: Camidge, MD
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H. Lee Moffitt Cancer Center & Research Institute
      • Contact: Ferreira, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
      • Contact: Janne, MD
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Not yet recruiting
      • Michigan Center of Medical Research
      • Contact: Balaraman, MD
  • New York
    • New Hyde Park, New York, United States, 11042-1118
      • Not yet recruiting
      • Northwell Health - Centers for Advanced Medicine
      • Contact: Seetharamu, MD
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: Doroshow, MD
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Recruiting
      • The Ohio State University Comprehensive Cancer Center
      • Contact: Otterson, MD
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
      • Contact: Spira, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Safety and tolerability of DZD9008.	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.	28 days after the first multiple dose
Part B: Objective Response Rate (ORR) according to RECIST 1.1.	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)	through the study completion, an average of around 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma DZD9008 concentration	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	Through cycle 3 day 1 (8 days for Cycle 0, 28 days for Cycle 1, then 21 days for each subsequent cycle)

Collaborators and Investigators

• Sponsor: Dizal Pharmaceuticals
• Investigators: Principal Investigator: Pasi Antero Janne, M.D & Ph. D, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2019
• Primary Completion (Estimated): October 1, 2023
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: May 21, 2019
• First Submitted That Met QC Criteria: June 3, 2019
• First Posted (Actual): June 4, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; mutation; HER2; EGFR
• 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: DZ2019E0001

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