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Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)

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ClinicalTrials.gov Identifier: NCT02864992
Recruitment Status : Active, not recruiting
First Posted : August 12, 2016
Results First Posted : June 9, 2023
Last Update Posted : June 9, 2023
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer (NSCLC) With MET Exon 14 (METex14) Skipping Alterations or MET Amplification Lung Adenocarcinoma Stage IIIB/IV Drug: Tepotinib Phase 2

Detailed Description:
The study included 3 cohorts with one primary endpoint (Objective Response Rate). Enrollment number and completion data is changed by new cohorts.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 337 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Single-arm Trial to Investigate Tepotinib in Advanced (Locally Advanced or Metastatic) Non-small Cell Lung Cancer With METex14 Skipping Alterations or MET Amplification (VISION)
Actual Study Start Date : September 13, 2016
Actual Primary Completion Date : May 16, 2022
Estimated Study Completion Date : February 20, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Part 1: Cohort A: METex14 Skipping Alterations
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.
 Drug: Tepotinib
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.
Part 1: Cohort B: MET Amplification
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.
 Drug: Tepotinib
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.
Part 2: Cohort C: Confirmatory Part for METex14 Skipping Alterations
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.
 Drug: Tepotinib
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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) ]
    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.

  2. 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) ]
    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.

  3. 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) ]
    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.


Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. Part 1 & 2: Cohort A + B + C: Overall Survival (OS) [ Time Frame: Time from first treatment up to end of study (approximately Month 101) ]
  8. 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) ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]
  13. 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) [ Time Frame: Time from first treatment up to end of study (approximately Month 101) ]
  14. 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) [ Time Frame: Time from first treatment up to end of study (approximately Month 101) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02864992


Locations
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Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible EMD Serono Research & Development Institute, Inc, a business of Merck KGaA, Darmstadt, Germany
  Study Documents (Full-Text)

Documents provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Study Protocol  [PDF] January 17, 2020
Statistical Analysis Plan  [PDF] March 31, 2022

More Information
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Additional Information:

Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT02864992    
Other Study ID Numbers: MS200095-0022
2015-005696-24 ( EudraCT Number )
First Posted: August 12, 2016    Key Record Dates
Results First Posted: June 9, 2023
Last Update Posted: June 9, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
URL: http://bit.ly/IPD21
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
lung
neoplasm
cancer
tumor
adenocarcinoma
MET exon 14
METex14
pulmonary
 stage III
stage IV
c-Met
cMET
NSCLC
advanced non-small cell lung cancer
MET amplification
non-small cell lung cancer
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Adenocarcinoma of Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
 Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Tepotinib
Antineoplastic Agents