NCT02864992 · CITED IN SOURCE DOCUMENTS

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-07-14

This study looked at how effective the study drug (tepotinib) was at stopping the growth and spread of lung cancer. This study also measures a number of other things including safety of the study drug and the side effects, how body processes the study drug, or how the study drug affects your quality of life. The study also has an optional pharmacogenetic research part. Pharmacogenetic research is an important way to try to understand the role of genetics in human disease and how genes impact the effectiveness of drugs, because differences in genes can change the way a person responds to a particular drug.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Part 1: Cohort A: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Independent Review Committee (IRC)

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outcome · POSTED

Part 1: Cohort B: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)

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outcome · POSTED

Part 2: Cohort C: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Duration of Response (DOR) Assessed by Investigator

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Duration of Response (DOR) Assessed by Investigator

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Objective Disease Control Rate Assessed by IRC

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Objective Disease Control Rate Assessed by Investigator

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Progression-free Survival by IRC Assessment

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B +C: Progression-free Survival by Investigator Assessment

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Overall Survival (OS)

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B +C: Number of Participants With Markedly Abnormal Clinical Laboratory Tests

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Number of Participants With Markedly Abnormal Vital Signs and Physical Examination

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiogram (ECG)

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Change From Baseline in Euro Quality of Life Questionnaire With 5 Questions Alternatives (EQ5D-5L) Summary Score

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

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outcome · NOT POSTED

Part 1 & 2: Cohort A + B + C: Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Signed, written informed consent by participant or legal representative prior to any trial-specific screening procedure * Male or female, greater than or equal to (\>=) 18 years of age (or have reached the age of majority according to local laws and regulations) * Measurable disease confirmed by an independent review committee (IRC) in accordance with RECIST version 1.1 * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 * A female participant was eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential OR * A woman of childbearing potential who agrees to use a highly effective contraception * A male participant must agree to use and to have their female partners of childbearing potential to use a highly effective contraception * Histologically or cytologically confirmed advanced (locally advanced or metastatic) NSCLC (all types including squamous and sarcomatoid) * Treatment naïve participant in first-line or pretreated participant with no more than 2 lines of prior therapy * Participants with MET alterations, namely METex14 skipping alterations in plasma and/or tissue as determined by the central laboratory or by an assay with appropriate regulatory status Exclusion Criteria: * Participants with characterized Epidermal Growth Factor Receptor (EGFR) activating mutations that predict sensitivity to anti-EGFR-therapy * Participants with characterized Anaplastic Lymphoma Kinase (ALK) rearrangements that predict sensitivity to anti-ALK therapy * Participants with symptomatic brain metastases who are neurologically unstable * Any unresolved toxicity Grade 2 or more according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) from previous anticancer therapy * Need for transfusion within 14 days prior to the first dose of trial treatment * Prior chemotherapy, biological therapy, radiation therapy, hormonal therapy for anti-cancer purposes, targeted therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment; * Participants who have brain metastasis as the only measurable lesion * Inadequate hematological, liver, renal, cardiac function * Prior treatment with other agents targeting the Hepatocyte Growth Factor c(HGF/c) -Met pathway * Hypertension uncontrolled by standard therapies (not stabilized to \< 150/90 mmHg) * Past or current history of neoplasm other than Non-small Cell Lung Cancer (NSCLC), except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years * Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the test product * Major surgery within 28 days prior to Day 1 of trial treatment * Known infection with human immunodeficiency virus, or an active infection with hepatitis B or hepatitis C virus * Substance abuse, active infection, or other acute or chronic medical or psychiatric condition or laboratory abnormalities that might increase the risk associated with trial participation at the discretion of Investigators * Known hypersensitivity to any of the trial treatment ingredients * Legal incapacity or limited legal capacity * Any other reason that, in the opinion of the Principal Investigator, precludes the participant from participating in the trial * Participation in another clinical trial within the past 30 days
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants received 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
intervention Names
Drug: Tepotinib
label
Part 1: Cohort A: METex14 Skipping Alterations
type
OTHER
description
Participants received 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
intervention Names
Drug: Tepotinib
label
Part 1: Cohort B: MET Amplification
type
OTHER
description
Participants received 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
intervention Names
Drug: Tepotinib
label
Part 2: Cohort C: Confirmatory Part for METex14 Skipping Alterations
type
OTHER

interventions

arm Group Labels
Part 1: Cohort A: METex14 Skipping Alterations
Part 1: Cohort B: MET Amplification
Part 2: Cohort C: Confirmatory Part for METex14 Skipping Alterations
description
Subjects will receive 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
name
Tepotinib
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 337
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Objective response will be determined according to RECIST 1.1 and as per IRC. Objective response was defined as number of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
measure
Part 1: Cohort A: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Independent Review Committee (IRC)
time Frame
Time from first treatment up to data cutoff (approximately Month 66)
description
Objective response will be determined according to RECIST 1.1 and as per IRC. Objective response was defined as number of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
measure
Part 1: Cohort B: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)
time Frame
Time from first treatment up to data cutoff (approximately Month 66)
description
Objective response will be determined according to RECIST 1.1 and as per IRC. Objective response was defined as number of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
measure
Part 2: Cohort C: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)
time Frame
Time from first treatment up to data cutoff (approximately Month 66)

secondary Outcomes

measure
Part 1 & 2: Cohort A + B + C: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B + C: Duration of Response (DOR) Assessed by Investigator
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B + C: Objective Disease Control Rate Assessed by IRC
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B + C: Objective Disease Control Rate Assessed by Investigator
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B + C: Progression-free Survival by IRC Assessment
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B +C: Progression-free Survival by Investigator Assessment
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B + C: Overall Survival (OS)
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B + C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B +C: Number of Participants With Markedly Abnormal Clinical Laboratory Tests
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B + C: Number of Participants With Markedly Abnormal Vital Signs and Physical Examination
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B + C: Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiogram (ECG)
time Frame
Time from first treatment up to end of study (approximately Month 101)
measure
Part 1 & 2: Cohort A + B + C: Change From Baseline in Euro Quality of Life Questionnaire With 5 Questions Alternatives (EQ5D-5L) Summary Score
time Frame
Time from first treatment up to end of study (approximately Month 101)

Full study description

brief Summary: This study looked at how effective the study drug (tepotinib) was at stopping the growth and spread of lung cancer. This study also measures a number of other things including safety of the study drug and the side effects, how body processes the study drug, or how the study drug affects your quality of life. The study also has an optional pharmacogenetic research part. Pharmacogenetic research is an important way to try to understand the role of genetics in human disease and how genes impact the effectiveness of drugs, because differences in genes can change the way a person responds to a particular drug.
detailed Description: The study included 3 cohorts with one primary endpoint (Objective Response Rate). Enrollment number and completion data is changed by new cohorts.

Source references

references

citation
Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC, Mazieres J, Viteri S, Senellart H, Van Meerbeeck J, Raskin J, Reinmuth N, Conte P, Kowalski D, Cho BC, Patel JD, Horn L, Griesinger F, Han JY, Kim YC, Chang GC, Tsai CL, Yang JC, Chen YM, Smit EF, van der Wekken AJ, Kato T, Juraeva D, Stroh C, Bruns R, Straub J, Johne A, Scheele J, Heymach JV, Le X. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020 Sep 3;383(10):931-943. doi: 10.1056/NEJMoa2004407. Epub 2020 May 29.
pmid
32469185
type
RESULT
citation
Kato T, Yang JC, Ahn MJ, Sakai H, Morise M, Chen YM, Han JY, Yang JJ, Zhao J, Hsia TC, Berghoff K, Bruns R, Vioix H, Lang S, Johne A, Le X, Paik PK. Efficacy and safety of tepotinib in Asian patients with advanced NSCLC with MET exon 14 skipping enrolled in VISION. Br J Cancer. 2024 Jun;130(10):1679-1686. doi: 10.1038/s41416-024-02615-9. Epub 2024 Apr 4.
pmid
38575731
type
DERIVED
citation
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pmid
37944528
type
DERIVED
citation
Mazieres J, Paik PK, Garassino MC, Le X, Sakai H, Veillon R, Smit EF, Cortot AB, Raskin J, Viteri S, Wu YL, Yang JCH, Ahn MJ, Ma R, Zhao J, O'Brate A, Berghoff K, Bruns R, Otto G, Johne A, Felip E, Thomas M. Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2023 Sep 1;9(9):1260-1266. doi: 10.1001/jamaoncol.2023.1962.
pmid
37270698
type
DERIVED
citation
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pmid
36999526
type
DERIVED
citation
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pmid
35771259
type
DERIVED
citation
Xiong W, Papasouliotis O, Jonsson EN, Strotmann R, Girard P. Population pharmacokinetic analysis of tepotinib, an oral MET kinase inhibitor, including data from the VISION study. Cancer Chemother Pharmacol. 2022 May;89(5):655-669. doi: 10.1007/s00280-022-04423-5. Epub 2022 Apr 6.
pmid
35385993
type
DERIVED