Lung Cancer Stage IIIPhase 2NUMERNCT06563999
Neoadjuvant Umbrella Trial for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations.
A Phase 2 study testing Sunvozertinib, Crizotinib and Pralsetinib in people with Lung Cancer Stage III and Mutation, run by Sun Yat-sen University at 1 site in China.
Trial summary
This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lung Cancer Stage III, Mutation
- What is being tested?
- Sunvozertinib, Crizotinib and Pralsetinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- 1 Nov 2024to 1 Nov 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have treatment-naive unresectable stage III NSCLC according to the AJCC 8th edition staging;
- Squamous or non-squamous NSCLC histology;
- Subjects should have a rare mutation based on NGS, including mutations of EGFR exon20ins, ROS1 fusion, RET fusion, NTRK fusion, MET 14 exon, HER2, BRAF V600E, KRAS G12C, and ALK fusion.
- Subjects should be without EGFR exon 19 deletions or exon 21 L858R activating mutation;
- Male and female, aged 18-75 years;
- Blood and specimens before and after treatment must be provided;
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
- Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level);
- Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN;
- Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min;
- Female subjects should not be pregnant or breast-feeding;
- Written informed consent provided. Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study.
Who cannot join
- Not unresectable stage III disease according to the investigator;
- Subjects with known EGFR sensitive mutations;
- Previous treatment with systemic antitumor therapy for NSCLC;
- Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.
- History of another malignancy in the last 5 years with the exception of the following: other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
- Evidence of clinically active interstitial lung disease;
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- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
- Inability to comply with protocol or study procedures;
- Any unstable systemic disease (including active infection, active tuberculosis uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease);
- A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study and may confuse the study results;
- Women who are pregnant or nursing.
- Ingredients mixed with small cell lung cancer patients.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Si-Yu Wang, Doctor, +86 20 87343439, wsysums@163.net
About this study
Official title: Neoadjuvant Umbrella Trial Directed by Next Generation Sequencing for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations (Without EGFR Sensitizing Mutations)
This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients whose tumor harbors a rare mutation.
Read the detailed description
Stage III non-small-cell lung cancer (NSCLC) patients account for about one-third of newly diagnosed NSCLC, with a large population and strong heterogeneity, posing significant challenges for clinical treatment. Concurrent chemoradiotherapy plus immune checkpoint inhibitors is the recommended therapeutic approach for patients with unresectable stage III non-small cell lung cancer (NSCLC), although surgery offers the chance of cure. However, existing evidence suggests that patients with driver mutation positive NSCLC have limited benefits from immunotherapy. There is still controversy over the definition of 'unresectable', and some stage IIIA and specific stage IIIB-N2 patients may also benefit from comprehensive surgical treatment. Emerging data supports the use of targeted therapies in NSCLC patients with a rare mutation. The aim of this umbrella study is to explore the efficacy of induction next generation sequencing (NGS)-directed targeted therapies followed by surgery for unresectable stage III NSCLC patients whose tumor harbors a rare mutation (Without EGFR Sensitizing Mutations).
- Conditions
- Lung Cancer Stage III, Mutation
- Being tested
- Sunvozertinib, Crizotinib, Pralsetinib, Larotrectinib, Savolitinib
- Keywords
- stage III NSCLC, rare mutations, umbrella trial, neoadjuvant
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunvozertinibDrug
Also called DZD9008
300 mg orally once a day, 28 days as one cycle.
CrizotinibDrug
Also called Xalkori
300 mg orally once a day, 28 days as one cycle.
PralsetinibDrug
Also called GAVRETO
400 mg orally once a day, 28 days as one cycle.
LarotrectinibDrug
Also called VITRAKVI
100 mg orally twice daily, 28 days as one cycle.
SavolitinibDrug
Also called ORPATHYS
600 mg or 400 mg (weight <50 kg) orally once a day, 28 days as one cycle.
PyrotinibDrug
Also called SHR1258
400 mg orally once a day, 28 days as one cycle.
Dabrafenib+TrametinibDrug
Dabrafenib 150 mg orally twice daily, 28 days as one cycle. Trametinib 150 mg orally twice daily, 28 days as one cycle.
GlecirasibDrug
Also called JAB-21822
800 mg daily orally, 28 days as one cycle.
EnsartinibDrug
Also called X-396
225 mg daily orally, 28 days as one cycle.
| Study group | Role | What they receive |
|---|---|---|
| Treatment 1-Sunvozertinib | Experimental | Patients with EGFR exon20ins mutation receive Sunvozertinib 300 mg orally once a day, 28 days as one cycle for 3 cycle. Receives: Drug: Sunvozertinib |
| Treatment 2-Crizotinib | Experimental | Patients with ROS1 fusion mutation receive Crizotinib 250mg orally once a day, 28 days as one cycle for 3 cycle. Receives: Drug: Crizotinib |
| Treatment 3-Pralsetinib | Experimental | Patients with RET fusion mutation receive Pralsetinib 400mg orally once a day, 28 days as one cycle for 3 cycle. Receives: Drug: Pralsetinib |
| Treatment 4-Larotrectinib | Experimental | Patients with NTRK fusion mutation receive Larotrectinib 100 mg orally twice daily, 28 days as one cycle for 3 cycle. Receives: Drug: Larotrectinib |
| Treatment 5-Savolitinib | Experimental | Patients with MET 14 exon mutation receive Savolitinib 600 mg or 400 mg (weight <50 kg) orally once a day, 28 days as one cycle for 3 cycle. Receives: Drug: Savolitinib |
| Treatment 6-Pyrotinib | Experimental | Patients with HER2 mutation receive Pyrotinib 400 mg orally once a day, 28 days as one cycle for 3 cycle. Receives: Drug: Pyrotinib |
| Treatment 7-Dabrafenib+Trametinib | Experimental | Patients with BRAF V600E mutation receive Dabrafenib plus Trametinib, 28 days as one cycle for 3 cycle. Receives: Drug: Dabrafenib+Trametinib |
| Treatment 8-Glecirasib | Experimental | Patients with KRAS G12C mutation receive Glecirasib 800 mg daily orally, 28 days as one cycle for 3 cycle. Receives: Drug: Glecirasib |
| Treatment 9-Ensartinib | Experimental | Patients with ALK fusion mutation receive Ensartinib 225 mg daily orally, 28 days as one cycle for 3 cycle. Receives: Drug: Ensartinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resectability rate
Measured: Baseline to 6 months
Secondary outcomes (4)
Adverse Events
Adverse Events were monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
Measured: Baseline to 24 months
Two-year disease-free survival
Disease-free survival was assessed from randomization to disease recurrence or death as a result of any cause.
Measured: 2 years after the last patient is randomized
Two-year overall survival
Overall survival was assessed from randomization to death as a result of any cause.
Measured: 2 years after the last patient is randomized
Number of participants with perioperative complications
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2024
- Study start1 Nov 2024
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Cancer Stage IIIStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Si-Yu Wang, Sun Yat-sen University
- Investigators
- Si-Yu Wang, MD, Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06563999
- Sponsor's protocol ID
- GASTO-10117
- Acronym
- NUMER
- Status last verified
- Apr 2026
- First submitted
- 19 Aug 2024
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Umbrella Trial Directed by Next Generation Sequencing for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations (Without EGFR Sensitizing Mutations)
- ClinicalTrials.gov ID
- NCT06563999
- Acronym / sponsor ID
- NUMER / GASTO-10117
- Conditions
- Lung Cancer Stage III, Mutation
- Keywords
- stage III NSCLC, rare mutations, umbrella trial, neoadjuvant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2029 (estimated)
- First posted
- 21 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients whose tumor harbors a rare mutation.
Detailed description
Stage III non-small-cell lung cancer (NSCLC) patients account for about one-third of newly diagnosed NSCLC, with a large population and strong heterogeneity, posing significant challenges for clinical treatment. Concurrent chemoradiotherapy plus immune checkpoint inhibitors is the recommended therapeutic approach for patients with unresectable stage III non-small cell lung cancer (NSCLC), although surgery offers the chance of cure. However, existing evidence suggests that patients with driver mutation positive NSCLC have limited benefits from immunotherapy. There is still controversy over the definition of 'unresectable', and some stage IIIA and specific stage IIIB-N2 patients may also benefit from comprehensive surgical treatment. Emerging data supports the use of targeted therapies in NSCLC patients with a rare mutation. The aim of this umbrella study is to explore the efficacy of induction next generation sequencing (NGS)-directed targeted therapies followed by surgery for unresectable stage III NSCLC patients whose tumor harbors a rare mutation (Without EGFR Sensitizing Mutations).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Treatment 1-Sunvozertinib | Experimental | Drug: SunvozertinibPatients with EGFR exon20ins mutation receive Sunvozertinib 300 mg orally once a day, 28 days as one cycle for 3 cycle. |
| Treatment 2-Crizotinib | Experimental | Drug: CrizotinibPatients with ROS1 fusion mutation receive Crizotinib 250mg orally once a day, 28 days as one cycle for 3 cycle. |
| Treatment 3-Pralsetinib | Experimental | Drug: PralsetinibPatients with RET fusion mutation receive Pralsetinib 400mg orally once a day, 28 days as one cycle for 3 cycle. |
| Treatment 4-Larotrectinib | Experimental | Drug: LarotrectinibPatients with NTRK fusion mutation receive Larotrectinib 100 mg orally twice daily, 28 days as one cycle for 3 cycle. |
| Treatment 5-Savolitinib | Experimental | Drug: SavolitinibPatients with MET 14 exon mutation receive Savolitinib 600 mg or 400 mg (weight <50 kg) orally once a day, 28 days as one cycle for 3 cycle. |
| Treatment 6-Pyrotinib | Experimental | Drug: PyrotinibPatients with HER2 mutation receive Pyrotinib 400 mg orally once a day, 28 days as one cycle for 3 cycle. |
| Treatment 7-Dabrafenib+Trametinib | Experimental | Drug: Dabrafenib+TrametinibPatients with BRAF V600E mutation receive Dabrafenib plus Trametinib, 28 days as one cycle for 3 cycle. |
| Treatment 8-Glecirasib | Experimental | Drug: GlecirasibPatients with KRAS G12C mutation receive Glecirasib 800 mg daily orally, 28 days as one cycle for 3 cycle. |
| Treatment 9-Ensartinib | Experimental | Drug: EnsartinibPatients with ALK fusion mutation receive Ensartinib 225 mg daily orally, 28 days as one cycle for 3 cycle. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subjects must have treatment-naive unresectable stage III NSCLC according to the AJCC 8th edition staging;
- Squamous or non-squamous NSCLC histology;
- Subjects should have a rare mutation based on NGS, including mutations of EGFR exon20ins, ROS1 fusion, RET fusion, NTRK fusion, MET 14 exon, HER2, BRAF V600E, KRAS G12C, and ALK fusion.
- Subjects should be without EGFR exon 19 deletions or exon 21 L858R activating mutation;
- Male and female, aged 18-75 years;
Key exclusion criteria (12 listed)
- Not unresectable stage III disease according to the investigator;
- Subjects with known EGFR sensitive mutations;
- Previous treatment with systemic antitumor therapy for NSCLC;
- Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.
- History of another malignancy in the last 5 years with the exception of the following: other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SunvozertinibAlso: DZD9008300 mg orally once a day, 28 days as one cycle. | Drug | Treatment 1-Sunvozertinib |
| CrizotinibAlso: Xalkori300 mg orally once a day, 28 days as one cycle. | Drug | Treatment 2-Crizotinib |
| PralsetinibAlso: GAVRETO400 mg orally once a day, 28 days as one cycle. | Drug | Treatment 3-Pralsetinib |
| LarotrectinibAlso: VITRAKVI100 mg orally twice daily, 28 days as one cycle. | Drug | Treatment 4-Larotrectinib |
| SavolitinibAlso: ORPATHYS600 mg or 400 mg (weight <50 kg) orally once a day, 28 days as one cycle. | Drug | Treatment 5-Savolitinib |
| PyrotinibAlso: SHR1258400 mg orally once a day, 28 days as one cycle. | Drug | Treatment 6-Pyrotinib |
| Dabrafenib+TrametinibDabrafenib 150 mg orally twice daily, 28 days as one cycle. Trametinib 150 mg orally twice daily, 28 days as one cycle. | Drug | Treatment 7-Dabrafenib+Trametinib |
| GlecirasibAlso: JAB-21822800 mg daily orally, 28 days as one cycle. | Drug | Treatment 8-Glecirasib |
| EnsartinibAlso: X-396225 mg daily orally, 28 days as one cycle. | Drug | Treatment 9-Ensartinib |
Primary outcome
Resectability rate
Time frame: Baseline to 6 months
4 secondary outcomes
Adverse Events
Time frame: Baseline to 24 months
Two-year disease-free survival
Time frame: 2 years after the last patient is randomized
Two-year overall survival
Time frame: 2 years after the last patient is randomized
Number of participants with perioperative complications
Time frame: Baseline to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Si-Yu Wang, MD principal investigator
Sun Yat-Sen University Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sunvozertinib, Crizotinib and Pralsetinib in people with Lung Cancer Stage III and Mutation, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Si-Yu Wang, MD (+86 20 87343439, wangsy@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resectability rate (time frame: Baseline to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2026.