Assessing an Oral EGFR Inhibitor, Sunvozertinib in Patients Who Have Advanced Non-small Cell Lung Cancer with EGFR or HER2 Mutation (WU-KONG1)
- Registration Number
- NCT03974022
- Lead Sponsor
- Dizal Pharmaceuticals
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 315
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Aged at least 18 years old, be able to provide a signed and dated, written informed consent.
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With documented histological or cytological confirmed locally advanced or metastatic NSCLC with EGFR or HER2 mutations.
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(ECOG) performance status 0-1.
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Predicted life expectancy ≥ 12 weeks
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Patient must have measurable disease according to RECIST 1.1.
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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.
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Adequate organ system function.
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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:
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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.
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Patients should have received at least 1 line, but no more than 3 lines of systemic therapy for metastatic/locally advanced disease.
- 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.
- 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.
- Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days before the first administration.
- 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.
- 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.
- 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.
- Spinal cord compression or leptomeningeal metastasis.
- 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).
- 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.
- 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.
- 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.
- History of hypersensitivity to active or inactive excipients of Sunvozertinib or drugs with a similar chemical structure or class to Sunvozertinib.
- Women who are pregnant or breast feeding.
- Involvement in the planning and conduct of the study.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part A Dose expansion cohort 6 Sunvozertinib - Part A Dose escalation Sunvozertinib - Part A Dose expansion cohort 2 Sunvozertinib - Part A Dose expansion cohort 1 Sunvozertinib - Part A Dose expansion cohort 4 Sunvozertinib Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy Part A Dose expansion cohort 3 Sunvozertinib Patients with EGFR Exon20ins, previously treated with at least one line of systemic therapy Part B Dose extension cohort 1 Sunvozertinib Patients with EGFR Exon20ins Part A Dose expansion cohort 5 Sunvozertinib Patients with EGFR Exon20ins, treatment naïve Part B Dose extension cohort 2 Sunvozertinib Patients with EGFR Exon20ins
- Primary Outcome Measures
Name Time Method Part B: Objective Response Rate (ORR) according to RECIST 1.1 by an Independent Review Committee (IRC). through the study completion, an average of around 1 year To evaluate anti-tumor activity of Sunvozertinib in advanced NSCLC patients with EGFR Exon20 insertion at defined dose(s) by assessment of Objective Response Rate (ORR).
Part A: Safety and tolerability of Sunvozertinib. 28 days after the first multiple dose To investigate the safety and tolerability of Sunvozertinib 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 Sunvozertinib when given orally in patients with advanced NSCLC with EGFR or HER2 mutations.
- Secondary Outcome Measures
Name Time Method Part A: Plasma Sunvozertinib concentrations, and derived PK parameters Through the study completion To evaluate the effect of food on the exposure of Sunvozertinib at the defined doses.
Part A: ORR, BOR, DoR, DCR, %change in size of tumor lesion, PFS by investigator. Through the study completion To assess preliminary anti-tumor activity of Sunvozertinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator.
Part A: ORR, DCR, DoR by IRC. Through the study completion To retrospectively assess anti-tumor activity of Sunvozertinib in patients with EGFR Exon20ins according to RECIST 1.1 by an Independent Review Committee (IRC).
Part A: Plasma and urine Sunvozertinib concentrations, and derived PK parameters. 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 Sunvozertinib following a single oral dosing and at steady state after multiple oral dosing in the fasted state, and renal excretion of Sunvozertinib.
Part B: Plasma Sunvozertinib and metabolite concentration and derived PK parameters if deemed appropriately. Through the study completion To characterize the PK of Sunvozertinib.
Part B: AEs/SAEs; Laboratory data; vital signs; physical examination; ECG; echocardiogram/MUGA; pulmonary function test. Through the study completion To determine the safety and tolerability of Sunvozertinib.
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. Through the study completion To assess anti-tumor efficacy of Sunvozertinib using additional endpoints.
Trial Locations
- Locations (124)
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST IRCCS
🇮🇹Meldola, Italy
Okayama University Hospital
🇯🇵Okayama-Shi, Japan
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Clínica Universidad de Navarra
🇪🇸Madrid, Spain
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Hospital La Fe
🇪🇸Valencia, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Hainan General Hospital
🇨🇳Haikou, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, China
The Affiliated Huaian No.1 Peoples Hospital of Nanjing Medical University
🇨🇳Huai'an, China
SAGA
🇨🇱Santiago, Chile
Fundacion Respirar - Consultorios Medicos Dr. Doreski
🇦🇷Cabildo, Argentina
CEMIC Centro de Educación Médica e Investigaciones Clínicas - Hospital Universitario sede Saavedra
🇦🇷Ciudad Autónoma Buenos Aires, Argentina
James Lind Centro De Investigacion Del Cancer
🇨🇱Temuco, Chile
Clinica Viedma S.A
🇦🇷Viedma, Argentina
Diabaid
🇦🇷Ciudad Autónoma Buenos Aires, Argentina
Centro de Investigación Pergamino SA
🇦🇷Pergamino, Argentina
Orlandi Oncología - Centro Médico Health & Care
🇨🇱Santiago, Chile
Niigata University Medical & Dental Hospital
🇯🇵Niigata-Shi, Japan
Tokyo Shinagawa Hospital
🇯🇵Tokyo, Japan
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chi Mei Hospital, Liouying
🇨🇳Liuying, Taiwan
Wan Fang Hospital
🇨🇳Taipei, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Azienda Ospedaliero - Universitaria "Policlinico - Vittorio Emanuele"
🇮🇹Catania, Italy
National Cancer Center
🇰🇷Goyang, Korea, Republic of
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Hunan Cancer Hospital
🇨🇳Changsha, China
HIA Begin
🇫🇷Saint-Mandé, France
Chris O'Brien Lifehouse
🇦🇺Camperdown, Australia
Fundación Arturo López Pérez
🇨🇱Providencia, Chile
AUSL Romagna - Ospedale S.M delle Croci
🇮🇹Ravenna, Italy
University of California, San Diego (UCSD) - Moores Cancer Center
🇺🇸La Jolla, California, United States
University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Innovative Clinical Research Institute, LLC
🇺🇸Whittier, California, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Michigan Center of Medical Research
🇺🇸Farmington Hills, Michigan, United States
The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Northwell Health - Centers for Advanced Medicine
🇺🇸New Hyde Park, New York, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Laura and Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
Centro Medico Austral OMI
🇦🇷Ciudad Autónoma Buenos Aires, Argentina
Fundacion CENIT Para La Investigacion en Neurociencias
🇦🇷Ciudad Autónoma Buenos Aires, Argentina
Instituto Argentino de Diagnositco y Tratamiento S.A.
🇦🇷Ciudad Autónoma Buenos Aires, Argentina
Instituto Medico de la Fundacion de Estudios Clínicos
🇦🇷Ciudad Autónoma Buenos Aires, Argentina
Blacktown Hospital
🇦🇺Blacktown, Australia
St George Hospital
🇦🇺Kogarah, Australia
Linear Cancer trials
🇦🇺Perth, Australia
Austin Hospital
🇦🇺Heidelberg, Australia
Peter MacCallum Cancer Centre - East Melbourne
🇦🇺North Melbourne, Australia
Southern Medical Day Care Centre
🇦🇺Wollongong, Australia
Princess Margaret Cancer Centre
🇨🇦Toronto, Canada
Peking Union Medical College Hospital
🇨🇳Beijing, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Beijing Chest Hospital，Capital Medical University
🇨🇳Beijing, China
Jilin Cancer Hospital
🇨🇳Changchun, China
West China Hospital of Sichuan University
🇨🇳Chengdu, China
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
The First Affilated Hospital of Zhejiang University
🇨🇳Hangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
The first Affiliated Hospital of USTC Anhui Provincial Hospital
🇨🇳Hefei, China
Henan Cancer Hospital
🇨🇳Henan, China
The Affiliated Hospital of Inner Mongolia Medical University
🇨🇳Hohhot, China
Jinan Central Hospital
🇨🇳Jinan, China
Linyi Cancer Hospital
🇨🇳Linyi, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, China
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, China
Guangxi Medical University Cancer Hospital
🇨🇳Nanning, China
Zhongshan Hospital, Fudan University
🇨🇳Shanghai, China
The First Hospital of China Medical University
🇨🇳Shenyang, China
Shanxi Cancer Hospital
🇨🇳Taiyuan, China
Taizhou Hospital of Zhejiang Province
🇨🇳Taizhou, China
Hubei Cancer Hospital
🇨🇳Wuhan, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
Centre Hospitalier Universitaire d'Angers
🇫🇷Angers, France
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, China
Hospices Civils de Lyon - Hôpital Louis Pradel
🇫🇷Bron, France
Centre Georges François Leclerc
🇫🇷Dijon, France
Hôpital de La Timone AP-Hm
🇫🇷Marseille, France
CHU de Lille - Institut Coeur Poumons
🇫🇷Hellemmes Lille, France
CHU de Montpellier Hôpital Arnaud de Villeneuve
🇫🇷Montpellier, France
APHP-Hôpital Bichat - Claude Bernard
🇫🇷Paris, France
CHU de Poitiers
🇫🇷Poitiers, France
Institut de Cancérologie de l'Ouest
🇫🇷Saint-Herblain, France
Centro di Riferimento Oncologico (CRO)
🇮🇹Aviano, Italy
CHU de Toulouse - Hôpital Larrey
🇫🇷Toulouse, France
Azienda Ospedaliero-Universitaria Careggi
🇮🇹Firenze, Italy
Institut Gustave ROUSSY
🇫🇷Villejuif, France
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Azienda Ospedaliero-Universitaria di Parma
🇮🇹Parma, Italy
Istituti Fisioterapici Ospitalieri
🇮🇹Roma, Italy
Aichi Cancer Center Hospital
🇯🇵Nagoya-Shi, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama-shi, Japan
Tokushima University Hospital
🇯🇵Tokushima-Shi, Japan
Chungbuk National University Hospital
🇰🇷Cheonju, Korea, Republic of
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
Centro Integral Oncológico Clara Campal (CIOCC)
🇪🇸Madrid, Spain
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Hospital Sultan Ismail
🇲🇾Johor Bahru, Malaysia
Hospital de Jeréz
🇪🇸Jerez de la Frontera, Spain
ICO (Institut Catala d'Oncologia) Badalona - Hospital Germans Trias i Pujol
🇪🇸Barcelona, Spain
Institut Català d'Oncología de Girona - Hospital Universitari de Girona Dr. Josep Trueta
🇪🇸Girona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen de Valme
🇪🇸Sevilla, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Fujian Cancer Hospital
🇨🇳Fuzhou, China