Clinical trial NCT03974022: Assessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer with EGFR or HER2 Mutation (WU-KONG1)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
EGFR
HER2
mutation
Lead sponsor: Dizal Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-06-04
Enrollment: 315
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: A Phase I/II, Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Efficacy of Sunvozertinib 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).

Eligibility 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 previously treated and stable, neurologically asymptomatic and does not require corticosteroid treatment.
7. Adequate organ system function.
8. Part A Dose expansion: 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 unless the patient had an objective response and subsequent progression assessed by the investigator.
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 the first administration of Sunvozertinib.
3. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before the first administration.
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 the first administration.
5. Receiving (or unable to stop using) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A within 1-2 weeks before the first administration.
6. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting Sunvozertinib with the exception of alopecia and grade 2 prior platinum-therapy related neuropathy.
7. Spinal cord compression or leptomeningeal metastasis.
8. 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, human immunodeficiency virus (HIV) and COVID-19 (per local practice).
9. Any of the following cardiac criteria: (1) Mean resting corrected QT interval (QTc) \> 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 QTF 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; (4) Prior history of atrial fibrillation within 6 months of first administration of Sunvozertinib, except prior drug treatment related and recovered.
10. 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.
11. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Sunvozertinib.
12. History of hypersensitivity to active or inactive excipients of Sunvozertinib or drugs with a similar chemical structure or class to Sunvozertinib.
13. Women who are pregnant or breast feeding.
14. Involvement in the planning and conduct of the study.
15. 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.

Primary outcomes:
measure: Part A: Safety and tolerability of Sunvozertinib.
timeFrame: 28 days after the first multiple dose
measure: Part B: Objective Response Rate (ORR) according to RECIST 1.1 by an Independent Review Committee (IRC).
timeFrame: through the study completion, an average of around 1 year
Secondary outcomes:
measure: Part A: Plasma and urine Sunvozertinib concentrations, and derived PK parameters.
timeFrame: Through cycle 3 day 1 (8 days for Cycle 0, 28 days for Cycle 1, then 21 days for each subsequent cycle)
measure: Part A: Plasma Sunvozertinib concentrations, and derived PK parameters
timeFrame: Through the study completion
measure: Part A: ORR, BOR, DoR, DCR, %change in size of tumor lesion, PFS by investigator.
timeFrame: Through the study completion
measure: Part A: ORR, DCR, DoR by IRC.
timeFrame: Through the study completion
measure: Part B: DoR, PFS, DCR, BOR and % of change in size of tumor lesion according to RECIST 1.1 using assessments performed by an IRC; DoR, PFS, DCR, BOR and % of change in size of tumor lesion using investigators assessments accord.
timeFrame: Through the study completion
measure: Part B: AEs/SAEs; Laboratory data; vital signs; physical examination; ECG; echocardiogram/MUGA; pulmonary function test.
timeFrame: Through the study completion
measure: Part B: Plasma Sunvozertinib and metabolite concentration and derived PK parameters if deemed appropriately.
timeFrame: Through the study completion
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego (UCSD) - Moores Cancer Center
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute, LLC
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: New Hyde Park
country: United States
facility: Northwell Health - Centers for Advanced Medicine
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Cabildo
country: Argentina
facility: Fundacion Respirar - Consultorios Medicos Dr. Doreski
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: CEMIC Centro de Educación Médica e Investigaciones Clínicas - Hospital Universitario sede Saavedra
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Centro Medico Austral OMI
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Diabaid
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Fundacion CENIT Para La Investigacion en Neurociencias
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Instituto Argentino de Diagnositco y Tratamiento S.A.
city: Ciudad Autónoma Buenos Aires
country: Argentina
facility: Instituto Medico de la Fundacion de Estudios Clínicos
city: Pergamino
country: Argentina
facility: Centro de Investigación Pergamino SA
city: Viedma
country: Argentina
facility: Clinica Viedma S.A
city: Blacktown
country: Australia
facility: Blacktown Hospital
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
city: Heidelberg
country: Australia
facility: Austin Hospital
city: Kogarah
country: Australia
facility: St George Hospital
city: North Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre - East Melbourne
city: Perth
country: Australia
facility: Linear Cancer trials
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Providencia
country: Chile
facility: Fundación Arturo López Pérez
city: Santiago
country: Chile
facility: Orlandi Oncología - Centro Médico Health & Care
city: Santiago
country: Chile
facility: SAGA
city: Temuco
country: Chile
facility: James Lind Centro De Investigacion Del Cancer
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Chest Hospital，Capital Medical University
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Haikou
country: China
facility: Hainan General Hospital
city: Hangzhou
country: China
facility: The First Affilated Hospital of Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Hefei
country: China
facility: The first Affiliated Hospital of USTC Anhui Provincial Hospital
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
city: Henan
country: China
facility: Henan Cancer Hospital
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
city: Huai'an
country: China
facility: The Affiliated Huaian No.1 Peoples Hospital of Nanjing Medical University
city: Jinan
country: China
facility: Jinan Central Hospital
city: Linyi
country: China
facility: Linyi Cancer Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
city: Bron
country: France
facility: Hospices Civils de Lyon - Hôpital Louis Pradel
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Hellemmes Lille
country: France
facility: CHU de Lille - Institut Coeur Poumons
city: Marseille
country: France
facility: Hôpital de La Timone AP-Hm
city: Montpellier
country: France
facility: CHU de Montpellier Hôpital Arnaud de Villeneuve
city: Paris
country: France
facility: APHP-Hôpital Bichat - Claude Bernard
city: Poitiers
country: France
facility: CHU de Poitiers
city: Saint-Herblain
country: France
facility: Institut de Cancérologie de l'Ouest
city: Saint-Mandé
country: France
facility: HIA Begin
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital Larrey
city: Villejuif
country: France
facility: Institut Gustave ROUSSY
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico (CRO)
city: Catania
country: Italy
facility: Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST IRCCS
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
city: Ravenna
country: Italy
facility: AUSL Romagna - Ospedale S.M delle Croci
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
city: Roma
country: Italy
facility: Istituti Fisioterapici Ospitalieri
city: Matsuyama-shi
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Nagoya-Shi
country: Japan
facility: Aichi Cancer Center Hospital
city: Niigata-Shi
country: Japan
facility: Niigata University Medical & Dental Hospital
city: Okayama-Shi
country: Japan
facility: Okayama University Hospital
city: Tokushima-Shi
country: Japan
facility: Tokushima University Hospital
city: Tokyo
country: Japan
facility: Tokyo Shinagawa Hospital
city: Cheonju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Goyang
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: ICO (Institut Catala d'Oncologia) Badalona - Hospital Germans Trias i Pujol
city: Girona
country: Spain
facility: Institut Català d'Oncología de Girona - Hospital Universitari de Girona Dr. Josep Trueta
city: Jerez de la Frontera
country: Spain
facility: Hospital de Jeréz
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal (CIOCC)
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital La Fe
city: Liuying
country: Taiwan
facility: Chi Mei Hospital, Liouying
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Wan Fang Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Pasi Antero Jänne, M.D & Ph. D
role: PRINCIPAL_INVESTIGATOR
References: