Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)

Merck KGaA (EMD Serono)

Status and phase: Active, not recruiting; Phase 2

Conditions: Lung Adenocarcinoma Stage IIIB/IV; Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer (NSCLC) With MET Exon 14 (METex14) Skipping Alterations or MET Amplification

Treatments: Drug: Tepotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02864992

MS200095-0022

2015-005696-24 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

The study included 3 cohorts with one primary endpoint (Objective Response Rate). Enrollment number and completion data is changed by new cohorts.

Enrollment: 337 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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337 participants in 3 patient groups

Part 1: Cohort A: METex14 Skipping Alterations

Other group

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.

Treatment:

Drug: Tepotinib

Part 1: Cohort B: MET Amplification

Other group

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.

Treatment:

Drug: Tepotinib

Part 2: Cohort C: Confirmatory Part for METex14 Skipping Alterations

Other group

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.

Treatment:

Drug: Tepotinib