Recruiting
Phase 3
A Phase 3 Study of Sunvozertinib Versus Placebo as Adjuvant Therapy in Patients With Early-Stage Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations or PACC Mutations After Radical Surgery
Condition(s) studied
Non-Small Cell Lung Cancer
Investigational drug(s) / intervention(s)
sunvozertinib: Participants will receive oral administration of sunvozertinib 200 mg QD following randomization, with each treatment cycle defined as 21 days, until meeting any treatment discontinuation criteria (i.e, objective disease recurrence, intolerable adverse event \[AE\], completion of 3-year \[156-week\] treatment period, study termination, death, treatment or study withdrawal by participants, whichever occurs first).
Matching Placebo: Participants will receive oral administration of placebo 200 mg QD following randomization, with each treatment cycle defined as 21 days, until meeting any treatment discontinuation criteria (i.e, objective disease recurrence, intolerable adverse event \[AE\], completion of 3-year \[156-week\] treatment period, study termination, death, treatment or study withdrawal by participants, whichever occurs first).
Study summary
To assess the efficacy and safety of sunvozertinib versus placebo as adjuvant therapy in patients with stage IB-IIIA non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins) or P-loop and αC-helix compression (PACC) mutations, who have had radical surgery, regardless of adjuvant chemotherapy.
Eligibility
Inclusion Criteria:
1. Provide a signed and dated informed consent form (ICF) prior to any study specific procedures, sampling, and analyses.
2. Aged at least 18 years old at the time of ICF signature.
3. Complete resection (R0) of the primary tumor and histologically confirmed diagnosis of NSCLC (participants with tumor histology indicative of neuroendocrine carcinoma, sarcomatoid carcinoma, or small cell lung cancer should be excluded).
* Complete surgical resection of the primary NSCLC is mandatory. All gross lesions must be completely resected to achieve microscopically negative margins. Hilar and mediastinal lymph node dissection should be performed per clinical guidelines.
* Acceptable surgery type: lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy.
* Acceptable surgery approach: thoracotomy or thoracoscopic surgery.
4. Participants must have NSCLC classified post-operatively as stage IB, II, or IIIA according to the AJCC TNM staging 9.0th edition.
5. Have documented EGFR exon20ins (Cohort 1) or EGFR PACC mutations (Cohort 2) from a local Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (or equivalent).
• Common EGFR PACC mutations include, but not limited to, L718Q, G719X, S768I, L747P/S, V769L, E709\_T710delinsD, L792H, and T854I.
6. Participants must provide sufficient tumor tissue samples for confirmation of EGFR mutations by the sponsor designated central laboratory.
7. ECOG performance status is 0 or 1.
8. Participants must recover from prior lung surgery and systemic therapy (e.g., neoadjuvant therapy and/or adjuvant chemotherapy) without Grade 1 or higher AEs (except alopecia of any grade and ≤ Grade 2 platinum-associated neuropathy) at randomization.
* Participants who have not previously received adjuvant chemotherapy should be randomized as early as 4 weeks and within 10 weeks after the radical surgery.
* Participants who have previously received adjuvant chemotherapy can be randomized within 2 - 10 weeks of completion of adjuvant chemotherapy with a maximum interval of no more than 26 weeks from surgery to randomization. The adjuvant chemotherapy can start as early as 4 weeks after the radical surgery, in 21-day cycles, and up to 4 cycles.
9. Adequate bone marrow reservation or organ functions within 7 days prior to randomization.
10. Male participants with female partners of child-bearing potential should use barrier contraceptives (e.g., by use of condoms), during their participation in this study and for 6 months following the last dose of the study drug. Male participants must refrain from donating sperm during their participation in the study and for 6 months following the last dose of the study drug. If male participants wish to father children, they should be advised to arrange for freezing of sperm samples prior to the start of study drug.
11. Female participants of child-bearing potential should use reliable contraceptives from the time of screening until 2 months after discontinuation of study drug. Female participants should not be breast feeding and must have a negative pregnancy test (serum or urine β-human chorionic gonadotropin) prior to start dosing or must fulfil one of the following criteria at screening:
* Post-menopausal defined as aged at least 50 years old and amenorrhea for at least 12 months following cessation of all exogenous hormonal treatment.
* Women under 50 years old would be considered postmenopausal if they have been amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range.
* Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
Exclusion Criteria:
1. Concurrent EGFR sensitizing mutations (L858R and/or exon 19 deletion) or other driver gene variations with available standard therapies (e.g., ALK positive).
2. Participants who have had only segmentectomies or wedge resections.
3. Participants who have received any preoperative or postoperative radiotherapy for NSCLC, or who plan to have radiotherapy during the study.
4. Participants who have received any EGFR TKIs as (neo)adjuvant therapy for NSCLC or have known pathological complete response from previous neoadjuvant therapy.
5. Participants who are receiving (or unable to stop) medications or herbs known to be strong CYP3A inducers within 2 weeks prior to randomization.
6. Previous history of interstitial lung disease (ILD), drug-induced ILD, or radiation pneumonitis requiring steroid therapy, any evidence of clinically active ILD, or immunotherapy induced pneumonitis.
7. Any serious or uncontrolled systemic disease requiring treatment, including uncontrolled hypertension, diabetes, chronic heart failure and active bleeding disorders (such as hemophilia, von Willebrand disease), etc., which in the opinion of the investigator is not suitable for participation in the trial or will affect compliance with the protocol; or active infection, including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
8. Any of the following cardiac criteria:
* Mean resting corrected QT interval (QTc) \> 470 msec on 3 ECGs at screening
* 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 old in first degree relatives or any concomitant medication known to prolong the QT interval.
* Prior history of atrial fibrillation within 6 months of the first dose of study drug, except for those related to drug treatment and recovered.
9. Participants with a history of any malignancy, except for adequately treated non-melanoma skin cancer, carcinoma in situ or other solid tumors with \>5 years since completion of anti-cancer therapy and no evidence of disease recurrence at randomization
10. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous major bowel resection that may preclude adequate absorption of sunvozertinib.
11. Hypersensitivity to sunvozertinib, excipients of sunvozertinib, or drugs of similar chemical structure or same class.
12. Involvement in the design, planning or conduct of this study (applicable to Dizal staff or study site staff).
13. Judgment by the investigator that the participant is unlikely to comply with study procedures, restrictions or requirements.
Primary outcome measure(s)
- Disease-free survival (DFS) by investigator assessment — Up to approximately 5 years after the first participant is randomized
Trial sites (49)
| Facility | City | Region | Status |
| Beijing Cancer Hospital |
Beijing |
China |
Not Yet Recruiting |
| Beijing Chest Hospital, Capital medical university |
Beijing |
China |
Not Yet Recruiting |
| Cancer Hospital Chinese Academy of Medical Sciences |
Beijing |
China |
Not Yet Recruiting |
| China-Japan Friendship hospital |
Beijing |
China |
Not Yet Recruiting |
| Peking Union Medical College Hospital |
Beijing |
China |
Not Yet Recruiting |
| Xuanwu Hospital Capital Medical University |
Beijing |
China |
Not Yet Recruiting |
| The First Hospital of Jilin University |
Changchun |
China |
Recruiting |
| Hunan Cancer Hospital |
Changsha |
China |
Not Yet Recruiting |
| The Third Xiangya Hospital of Central South University |
Changsha |
China |
Not Yet Recruiting |
| Xiangya Hospital of Central South University |
Changsha |
China |
Not Yet Recruiting |
| Sichuan Cancer Hospital |
Chengdu |
China |
Not Yet Recruiting |
| West China Hospital Sichuan University |
Chengdu |
China |
Not Yet Recruiting |
| Fujian Cancer Hospital |
Fuzhou |
China |
Not Yet Recruiting |
| Fujian Medical University Union Hospital |
Fuzhou |
China |
Not Yet Recruiting |
| Affiliated Cancer Hospital and Institute of Guangzhou Medical University |
Guangzhou |
China |
Not Yet Recruiting |
| Sun Yat-sen Memorial Hospital, Sun Yat-sen University |
Guangzhou |
China |
Not Yet Recruiting |
| Sun Yat-sen University Cancer Center |
Guangzhou |
China |
Not Yet Recruiting |
| The First Affiliated Hospital of Guangzhou Medical University |
Guangzhou |
China |
Not Yet Recruiting |
| The First Affiliated Hospital Zhejiang University School of Medicine |
Hangzhou |
China |
Not Yet Recruiting |
| The Second Affiliated Hospital Zhejiang University School of Medicine |
Hangzhou |
China |
Not Yet Recruiting |
| Zhejiang Cancer Hospital |
Hangzhou |
China |
Not Yet Recruiting |
| Harbin Medical University Cancer Hospital |
Harbin |
China |
Not Yet Recruiting |
| Anhui Provincial Cancer Hospital |
Hefei |
China |
Recruiting |
| Jinan Central Hospital |
Jinan |
China |
Not Yet Recruiting |
| Shandong Cancer Hospital |
Jinan |
China |
Recruiting |
| Yunnan Cancer Hospital |
Kunming |
China |
Not Yet Recruiting |
| Jiangxi Provincial People 's Hospital |
Nanchang |
China |
Not Yet Recruiting |
| Jiangsu Province Hospital |
Nanjing |
China |
Not Yet Recruiting |
| Nanjing Chest Hospital |
Nanjing |
China |
Not Yet Recruiting |
| Guangxi Medical University Cancer Hospital |
Nanning |
China |
Not Yet Recruiting |
| Fudan University Shanghai Cancer Center |
Shanghai |
China |
Not Yet Recruiting |
| Shanghai Chest Hospital |
Shanghai |
China |
Not Yet Recruiting |
| Shanghai East Hospital |
Shanghai |
China |
Not Yet Recruiting |
| Shanghai Pulmonary Hospital |
Shanghai |
China |
Recruiting |
| Zhongshan Hospital Fudan University |
Shanghai |
China |
Not Yet Recruiting |
| Liaoning Cancer Hospital & Institute |
Shenyang |
China |
Not Yet Recruiting |
| The First Hospital of China Medical University |
Shenyang |
China |
Not Yet Recruiting |
| Shanxi Cancer hospital (Shanxi Cancer institute) |
Taiyuan |
China |
Not Yet Recruiting |
| Shanxi Provincial people's hospital |
Taiyuan |
China |
Not Yet Recruiting |
| Taizhou Hospital, Zhejiang Province |
Taizhou |
China |
Not Yet Recruiting |
+ 9 more sites — see the full list on the official registry below.
Other trials for the same condition