Clinical trial NCT04677595: Study of Capmatinib in Chinese Adult Patients With Advanced Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation
Official title: A Phase II, Multicenter, Two-cohort Study of Oral MET Inhibitor Capmatinib in Chinese Adult Patients With EGFR Wild-type (wt), ALK Rearrangement Negative, MET Exon 14 Skipping Mutations, Advanced Non-small Cell Lung Cancer (NSCLC) Who Are Treatment Naive or Failed One or Two Prior Lines of Systemic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer (NSCLC)
Keywords: Non small cell lung cancer
Non small cell carcinoma
INC280
capmatinib
NSCLC
MET mutation
MET exon14
EGFTwt
ALK negative
Epidermal growth factor receptor wild type
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-12-21
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to learn whether the study treatment (capmatinib), which already shows efficacy and safety in non-Chinese patients, could help Chinese patients with controlling their lung cancer in a safe way. Participants will have a type of lung cancer called non-small cell lung lancer (NSCLC), with a specific alteration in a part of their DNA (called mutation) of the MET gene, within a specific part of this gene called exon 14.

Participants who have advanced (or metastatic) non-small cell lung cancer with specific mutations in the MET gene but without mutations in the EGFR or ALK genes, who are aged 18 years or older will be enrolled in this study.

The study drug, capmatinib (also known as INC280), is an oral drug that is called a 'targeted' medicine, which means it targets particular processes that may not be working properly in cancer cells (called dysregulation). The dysregulation of the MET signaling in cancer cells of patients with NSCLC is believed to make the cancer worse. Capmatinib has been shown to selectively block the effects of the MET gene and therefore may help in keeping the disease under control, stopping cancer cells from growing.

Detailed description: This is an open-label, multicenter two-cohort phase II study. Chinese adult participants with EGFR wild-type (wt) (EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations), anaplastic lymphoma kinase (ALK) rearrangement negative, advanced (stage IIIB, IIIC or IV) NSCLC disease harboring MET exon 14-skipping (METΔex14) mutations as determined by a Novartis central molecular laboratory will be treated in this study. Cohort 1 will include treatment naive participants and Cohort 2 participants who failed one or two prior lines of therapy in the advanced stage (stage IIIB, IIIC or IV). Each participant will receive 400 mg capmatinib tablet twice daily (BID).

The primary endpoint is the overall response rate (ORR) by cohort as per the blinded independent review committee (BIRC) review. ORR is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) according to RECIST 1.1.

The primary analysis will be performed using full analysis set (FAS). The primary efficacy endpoint ORR will be estimated and the exact 95% confidence interval (CI) will be provided by cohort.

Eligibility criteria: Key Inclusion Criteria:

* Chinese adult ≥ 18 years old at the time of informed consent
* Histologically confirmed stage IIIB, IIIC or IV NSCLC at the time of study entry, not amenable to curative surgery or radiation or multi-modality therapy (according to staging definition in CSCO guidelines for primary lung cancer, 2019).
* Histologically or cytologically confirmed diagnosis of NSCLC that is:

  1. EGFR wt: The EGFR wt status assessed as part of standard of care (EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 L858R substitution mutations)
  2. AND ALK rearrangement negative: assessed as part of standard of care by validated test
  3. AND either:

Cohort 1: Treatment naive participants with MET mutations, or Cohort 2: Pre-treated participants with MET mutations

* Cohort 1: participants must not have received any systemic therapy for advanced/metastatic disease (stage IIIB, IIIC or IV NSCLC). Neo-adjuvant and adjuvant systemic therapies will not count as one prior line of treatment if relapse occurred \> 12 months from the end of the neo-adjuvant or adjuvant systemic therapy.
* Cohort 2: participants must have failed one or two prior lines of systemic therapy for advanced/metastatic disease (stage IIIB, IIIC or IV NSCLC).
* At least one measurable lesion according to RECIST v1.1.
* Adequate organ function
* ECOG performance status (PS) ≤1

Key Exclusion Criteria:

* Prior treatment with any MET inhibitor or HGF-targeting therapy.
* Known druggable molecular alterations (such as ROS1 translocation or BRAF mutation, etc.) which might be a candidate for alternative targeted therapies as applicable per local regulations and treatment guidelines.
* Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
* Presence or history of interstitial lung disease or interstitial pneumonitis, including, clinically significant radiation pneumonitis affecting activities of daily living or requiring therapeutic intervention.
* Substance abuse, active infection (including active hepatitis B and C, participants whose disease is controlled under antiviral therapy are eligible, and human immunodeficiency virus (HIV) history positive) or other severe, acute, or chronic medical or psychotic conditions or laboratory abnormalities that in the opinion of the investigator may increase the risk associated with study participation, or that may interfere with the interpretation of study results.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Overall response rate (ORR) by blinded independent review committee (BIRC) assessment, by cohort
timeFrame: Up to approximately 23 months
Secondary outcomes:
measure: Duration of response (DOR) as assessed by BIRC, by cohort
timeFrame: From first documented response to first documented progression or death due to any cause, whichever comes first, assessed up to approximately 23 months
measure: Overall response rate (ORR) and duration of response (DOR) by investigator assessment, by cohort
timeFrame: Up to approximately 23 months
measure: Time to response (TTR) by investigator and by BIRC assessment, by cohort
timeFrame: From first dose to first documented response of either CR or PR, assessed up to approximately 23 months
measure: Disease Control Rate (DCR) by investigator and by BIRC assessment, by cohort
timeFrame: Up to approximately 23 months
measure: Progression Free Survival (PFS) by investigator and by BIRC assessment, by cohort
timeFrame: From first dose to the date of first documented progression or death from any cause, whichever comes first, assessed up to approximately 23 months
measure: Overall survival (OS)
timeFrame: From first dose to death due to any cause, assessed up to approximately 42 months
measure: Overall intracranial response rate (OIRR)
timeFrame: Up to approximately 23 months
measure: Intracranial disease control rate (IDCR)
timeFrame: Up to approximately 23 months
measure: Time to intracranial response (TTIR)
timeFrame: Up to approximately 23 months
measure: Duration of intracranial response (DOIR)
timeFrame: Up to approximately 23 months
measure: Association between MET mutation status as measured in ctDNA at baseline with capmatinib efficacy
timeFrame: Up to approximately 23 months
measure: Plasma capmatinib concentration
timeFrame: Cycle 2 Day 1 pre-dose, 0.5-1.5 hours post-dose and 3-5 hours post dose and Cycle 3 Day 1 pre-dose. Each cycle duration is 21 days
measure: Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
timeFrame: Cycle 1 Day 1, Cycle 3 Day 1 and then every 6 weeks up to approximately 23 months. Each cycle duration is 21 days.
measure: Change from baseline in score as per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Lung Cancer Module (QLQ-LC13)
timeFrame: Cycle 1 Day 1, Cycle 3 Day 1 and then every 6 weeks up to approximately 23 months. Each cycle duration is 21 days.
measure: Change from baseline in score as per European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) questionnaire
timeFrame: Cycle 1 Day 1, Cycle 3 Day 1 and then every 6 weeks up to approximately 23 months. Each cycle duration is 21 days.
measure: Time to deterioration in symptoms of brain metastases, with the NCCN FACT-Brain Symptom Index symptom module (FBrSI)
timeFrame: Cycle 1 Day 1, Cycle 3 Day 1 and then every 6 weeks up to approximately 23 months. Each cycle duration is 21 days.
Other outcomes:
Locations:
city: Xiamen
country: China
facility: Novartis Investigative Site
state: Fujian
city: Foshan
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guang Zhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Harbin
country: China
facility: Novartis Investigative Site
state: Heilongjiang
city: Zhengzhou
country: China
facility: Novartis Investigative Site
state: Henan
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Shenyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Jinan
country: China
facility: Novartis Investigative Site
state: Shandong
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Urumchi
country: China
facility: Novartis Investigative Site
state: Xinjiang
city: Kunming
country: China
facility: Novartis Investigative Site
state: Yunnan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
Study officials:
References: