Non-small Cell Lung CancerPhase 2Geometry-NNCT04926831
Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC
A Phase 2 study testing capmatinib in people with Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 6 sites in United States.
Trial summary
This study was planned to determine if neoadjuvant capmatinib could improve the major pathological response (MPR) in patients with Stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2) lung cancers with Mesenchymal Epithelial Transition (MET) exon 14 mutations and/or high MET amplification beyond those achieved with… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- capmatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 6 sitesUnited States
- Study dates
- 10 Aug 2022to 13 Mar 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult ≥ 18 years of age at the time of informed consent.
- Histologically confirmed NSCLC Stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2) (per AJCC 8th edition), deemed suitable for primary resection by treating surgeon (T4 tumors with mediastinal organ invasion were not eligible for enrollment).
- Participant must have MET exon 14 mutation and/or high-level MET amplification (MET: GCN ≥ 10) as determined by a CLIA certified laboratory. High level MET amplification must be identified by FISH in a CLIA certified laboratory or FoundationOne CDx NGS (other NGS-based methods without adjusting for tumor content % cannot be accepted).
- Participants must be eligible for surgery and scheduled for surgical resection within approximately 2 weeks after the last dose of neoadjuvant study treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Who cannot join
- Participants with unresectable or metastatic disease. All participants should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment to exclude brain metastasis.
- Presence or history of a malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- Prior treatment with any MET inhibitor or HGF-targeting therapy.
- Participants with other known oncogenic driver alterations.
- Prior systemic anti-cancer therapy (chemotherapy, immunotherapy, biologic therapy, vaccine) or investigational agents for NSCLC.
- Participants with known hypersensitivity to capmatinib and any of the excipients of capmatinib (crospovidone, mannitol, microcrystalline cellulose, povidone, sodium lauryl sulfate, magnesium stearate, colloidal silicon dioxide, and various coating premixes).
- Other protocol-defined inclusion/exclusion criteria may apply at the end
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Fairfax Northern Virginia Hem Onc .
Fairfax, Virginia, 22031
Fairfax Northern Virginia Hem Onc
Fairfax, Virginia, 22031
UCLA Oncology Hematology .
La Jolla, California, 92037
UCLA Oncology Hematology
La Jolla, California, 92037
University of California Davis Cancer Center .
Sacramento, California, 95817
University of California Davis Cancer Center
Sacramento, California, 95817
About this study
Official title: Phase II Trial of Neoadjuvant and Adjuvant Capmatinib in Participants With Stages IB-IIIA, N2 and Selected IIIB (T3N2 or T4N2) NSCLC With MET Exon 14 Skipping Mutation or High MET Amplification (Geometry-N)
This study was planned to determine if neoadjuvant capmatinib could improve the major pathological response (MPR) in patients with Stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2) lung cancers with Mesenchymal Epithelial Transition (MET) exon 14 mutations and/or high MET amplification beyond those achieved with surgery, chemotherapy, and radiation. Treatment was to be continued with capmatinib in the adjuvant setting to evaluate the potential clinical benefit of extended therapy.
The purpose of this study is to determine if neoadjuvant capmatinib can improve outcomes in participants with stages I-IIIA non-small cell lung cancer with MET exon 14 mutations and/or high MET amplification beyond those achieved with surgery, chemotherapy, and radiation.
Read the detailed description
This was a Phase II, two cohort, two stage study of capmatinib given for 8 weeks (2 cycles) prior to surgical resection, followed by three-year capmatinib treatment in adjuvant setting. Surgery had to be performed up to 2 weeks after the last dose of neoadjuvant study treatment.
There were 2 molecularly defined cohorts enrolled in parallel:
- Cohort A: MET exon 14 skipping mutations, irrespective of MET GCN or
- Cohort B: high level MET amplification (MET: GCN ≥ 10 by FISH or FoundationOne CDx NGS using tumor tissue).
Approximately 42 participants were aimed to be enrolled in the study, with 21 participants per cohort. This was planned to obtain 38 evaluable participants, 19 per each cohort. Participants who had both MET exon 14 skipping mutations and high-level MET amplification were planned to be enrolled into Cohort A. An evaluable subject received the neoadjuvant treatment and subsequently underwent surgery, resulting in a pathological response.
The study recruitment was prematurely discontinued due to significant recruitment challenges leading to termination of the study. The challenges included the rarity of the mutation and site initiation delays caused by staff shortages associated with COVID-19. As a result, only 4 subjects were enrolled and treated in Cohort A.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- capmatinib
- Keywords
- Mesenchymal Epithelial Transition (MET), MET exon 14 skipping mutation, High MET amplification, Neoadjuvant, Prior to surgery, Adjuvant, After surgery, INC280, MET inhibition, adult, capmatinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
capmatinibDrug
Also called INC280
150 mg and 200 mg tablets for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (MET exon 14 skipping mutations) | Experimental | The study treatment started on Cycle 1 Day 1 with the first administration of capmatinib 400 mg twice a day (b.i.d.). The participants were planned to receive study treatment for a maximum of 3 years following surgery or until early discontinuation. Receives: Drug: capmatinib |
| Cohort B (high MET amplification) | Experimental | The study treatment started on Cycle 1 Day 1 with the first administration of capmatinib 400 mg twice a day (b.i.d.). The participants were planned to receive study treatment for a maximum of 3 years following surgery or until early discontinuation. Receives: Drug: capmatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Pathological Response (MPR) Rate
The primary efficacy variable was MPR rate, defined as the proportion of participants with ≤ 10% residual viable cancer cells. MPR rate was to be assessed via local review for primary analysis. MPR assessment in tumor samples was collected at time of resection.
Due to low number of participants and limited data, analysis related to the primary endpoint was not performed.
Measured: Baseline up to time of surgery (approximately 8 to 10 weeks after first dose)
Secondary outcomes (4)
Overall Response Rate (ORR)
Overall Response Rate (ORR) was defined as the percentage participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response ( PR) according to RECIST v1.1. BOR was the observed response at the assessment performed prior to surgery via local review.
Measured: Baseline up to time of surgery (approximately 8 - 10 weeks after first dose)
Complete Pathologic Response (pCR) Rate
Complete pathologic response (pCR) rate ws defined as the percentage of participants with no residual viable cancer cells. pCR rate was assessed via both central and local review.
Measured: Baseline up to time of surgery (approximately. 8- 10 weeks after first dose)
Disease Free Survival (DFS)
Disease Free Survival (DFS) was defined as the time from the date of first adjuvant treatment to the date of the first documented disease recurrence as assessed by local investigator radiologically or death due to any cause. In case of non-conclusive radiological evidence, a biopsy was to be performed to confirm recurrence and used as DFS event. DFS events were assessed locally.
Measured: From time of surgery to Months 24, 36, and 60
Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Treatment emergent Adverse Event (TEAEs) in this study were events that started after the first dose of study treatment and until 30 days after the last dose of study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 30 days after the last study treatment.
Measured: Baseline up to 30 days after last dose of study medication, assessed up to approximately 20 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2021
- Study start10 Aug 2022
- Primary completion13 Mar 2024
- Study completion13 Mar 2024
Why it stopped: The study was terminated early due to recruitment challenges.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04926831
- Sponsor's protocol ID
- CINC280AUS12
- Acronym
- Geometry-N
- Status last verified
- Oct 2025
- First submitted
- 14 Jun 2021
- Last updated
- 16 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Neoadjuvant and Adjuvant Capmatinib in Participants With Stages IB-IIIA, N2 and Selected IIIB (T3N2 or T4N2) NSCLC With MET Exon 14 Skipping Mutation or High MET Amplification (Geometry-N)
- ClinicalTrials.gov ID
- NCT04926831
- Acronym / sponsor ID
- Geometry-N / CINC280AUS12
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- Mesenchymal Epithelial Transition (MET), MET exon 14 skipping mutation, High MET amplification, Neoadjuvant, Prior to surgery, Adjuvant, After surgery, INC280
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to recruitment challenges.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 10 Aug 2022 (actual)
- Primary completion
- 13 Mar 2024 (actual)
- Study completion
- 13 Mar 2024 (actual)
- First posted
- 15 Jun 2021 (actual)
- Results
- Posted 26 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was planned to determine if neoadjuvant capmatinib could improve the major pathological response (MPR) in patients with Stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2) lung cancers with Mesenchymal Epithelial Transition (MET) exon 14 mutations and/or high MET amplification beyond those achieved with surgery, chemotherapy, and radiation. Treatment was to be continued with capmatinib in the adjuvant setting to evaluate the potential clinical benefit of extended therapy.
The purpose of this study is to determine if neoadjuvant capmatinib can improve outcomes in participants with stages I-IIIA non-small cell lung cancer with MET exon 14 mutations and/or high MET amplification beyond those achieved with surgery, chemotherapy, and radiation.
Detailed description
This was a Phase II, two cohort, two stage study of capmatinib given for 8 weeks (2 cycles) prior to surgical resection, followed by three-year capmatinib treatment in adjuvant setting. Surgery had to be performed up to 2 weeks after the last dose of neoadjuvant study treatment.
There were 2 molecularly defined cohorts enrolled in parallel:
- Cohort A: MET exon 14 skipping mutations, irrespective of MET GCN or
- Cohort B: high level MET amplification (MET: GCN ≥ 10 by FISH or FoundationOne CDx NGS using tumor tissue).
Approximately 42 participants were aimed to be enrolled in the study, with 21 participants per cohort. This was planned to obtain 38 evaluable participants, 19 per each cohort. Participants who had both MET exon 14 skipping mutations and high-level MET amplification were planned to be enrolled into Cohort A. An evaluable subject received the neoadjuvant treatment and subsequently underwent surgery, resulting in a pathological response.
The study recruitment was prematurely discontinued due to significant recruitment challenges leading to termination of the study. The challenges included the rarity of the mutation and site initiation delays caused by staff shortages associated with COVID-19. As a result, only 4 subjects were enrolled and treated in Cohort A.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A (MET exon 14 skipping mutations) | Experimental | Drug: capmatinibThe study treatment started on Cycle 1 Day 1 with the first administration of capmatinib 400 mg twice a day (b.i.d.). The participants were planned to receive study treatment for a maximum of 3 years following surgery or until early discontinuation. |
| Cohort B (high MET amplification) | Experimental | Drug: capmatinibThe study treatment started on Cycle 1 Day 1 with the first administration of capmatinib 400 mg twice a day (b.i.d.). The participants were planned to receive study treatment for a maximum of 3 years following surgery or until early discontinuation. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult ≥ 18 years of age at the time of informed consent.
- Histologically confirmed NSCLC Stage IB-IIIA, N2 and selected IIIB (T3N2 or T4N2) (per AJCC 8th edition), deemed suitable for primary resection by treating surgeon (T4 tumors with mediastinal organ invasion were not eligible for enrollment).
- Participant must have MET exon 14 mutation and/or high-level MET amplification (MET: GCN ≥ 10) as determined by a CLIA certified laboratory. High level MET amplification must be identified by FISH in a CLIA certified laboratory or FoundationOne CDx NGS (other NGS-based methods without adjusting for tumor content % cannot be accepted).
- Participants must be eligible for surgery and scheduled for surgical resection within approximately 2 weeks after the last dose of neoadjuvant study treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
Key exclusion criteria (7 listed)
- Participants with unresectable or metastatic disease. All participants should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment to exclude brain metastasis.
- Presence or history of a malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- Prior treatment with any MET inhibitor or HGF-targeting therapy.
- Participants with other known oncogenic driver alterations.
- Prior systemic anti-cancer therapy (chemotherapy, immunotherapy, biologic therapy, vaccine) or investigational agents for NSCLC.
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 |
|---|---|---|
| capmatinibAlso: INC280150 mg and 200 mg tablets for oral administration | Drug | Cohort A (MET exon 14 skipping mutations), Cohort B (high MET amplification) |
Primary outcome
Major Pathological Response (MPR) Rate
Time frame: Baseline up to time of surgery (approximately 8 to 10 weeks after first dose)
The primary efficacy variable was MPR rate, defined as the proportion of participants with ≤ 10% residual viable cancer cells. MPR rate was to be assessed via local review for primary analysis. MPR assessment in tumor samples was collected at time of resection. Due to low number of participants and limited data, analysis related to the primary endpoint was not performed.
4 secondary outcomes
Overall Response Rate (ORR)
Time frame: Baseline up to time of surgery (approximately 8 - 10 weeks after first dose)
Complete Pathologic Response (pCR) Rate
Time frame: Baseline up to time of surgery (approximately. 8- 10 weeks after first dose)
Disease Free Survival (DFS)
Time frame: From time of surgery to Months 24, 36, and 60
Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
Time frame: Baseline up to 30 days after last dose of study medication, assessed up to approximately 20 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
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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. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing capmatinib in people with Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 6 sites in United States.
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 5 inclusion and 7 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: stopped early, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. 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?
Yes. Results are posted in the registry (first posted 26 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Pathological Response (MPR) Rate (time frame: Baseline up to time of surgery (approximately 8 to 10 weeks after first dose)). 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 16 Oct 2025.