Tepotinib Phase II study in advanced lung cancer harboring MET exon 14 (METex14) skipping alterations and MET amplificatio

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Cancer [C04]; Advanced (stage IIIB/IV) non-small cell lung cancer with MET exon 14 (METex14) skipping alterations; MedDRA version: 21.0Level: LLTClassification code 10001165Term: Adenocarcinoma lung stage IVSystem Organ Class: 100000004864; MedDRA version: 20.0Level: LLTClassification code 10001160Term: Adenocarcinoma lungSystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10001164Term: Adenocarcinoma lung stage IIISystem Organ Class: 100000004864

• Registration Number: EUCTR2015-005696-24-IT
• Lead Sponsor: MERCK KGAA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-25
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Histologically confirmed advanced adenocarcinoma of the lung, having failed at least one but not more than 2 lines of systemic therapy, including a platinum-doublet-containing regimen, but having failed a maximum of 2 lines of active therapy;
2. METex14 skipping alterations, as determined by the central laboratory. Both, archival and
fresh biopsies are acceptable; In case METex14 skipping alteration has been observed in a subject in a pre-trial setting, it should be ensured that sufficient tissue is available for re-testing before trial entry. Only subjects with METex14 skipping mutation based on trial central testing will be
enrolled into the trial.
3. Signed, written informed consent by subject or legal representative prior to any trial-specific screening procedure;
4. Male or female, = 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18 years of age);
5. Measurable disease in accordance with RECIST version 1.1;
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
7. A female subjects is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
a. Not a woman of childbearing potential as defined in Appendix VIII
OR
b. A woman of childbearing potential who agrees to use a highly
effective contraception (i.e., methods with a failure rate of less than 1 %
per year) as detailed in in Appendix VII of this protocol 2 weeks before
start of first dose of study treatment, during the treatment period and
for at least 4 weeks after the last dose of study treatment. Women of
childbearing potential must have a negative pregnancy test (ß-HCG test
in serum) prior to enrollment.
8. A male subject must agree to use and to have their female partners of
childbearing potential to use a highly effective contraception (i.e.,
methods with a failure rate of less than 1 % per year) as detailed in
Appendix VII of this protocol from the first dose of study treatment,
during the treatment period and for at least 3 months after the last dose
of study treatment and refrain from donating sperm during this period.
Male subjects should always use a barrier method such as condom
concomitantly
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Subjects with characterized EGFR (documented results; local testing acceptable) that predict sensitivity to EGFR-therapy, including, but not limited to exon 19 deletions and exon 21 alterations;
2. Subjects with characterized ALK rearrangements (documented results; local testing acceptable);
3. Active brain metastases (defined as neurologically stable for < 4 weeks and/or symptomatic and/or requiring treatment with steroids and/or leptomeningeal disease). Subjects must have completed any prior treatment for brain metastases = 4 weeks prior to start of therapy (= 2 weeks for stereotactic radiosurgery/gamma knife). Subjects who are neurologically stable on symptomatic therapy with anticonvulsants with low drug interaction risk or whose steroids
are being tapered are eligible. Asymptomatic untreated brain metastases = 1cm are eligible;
4. Any unresolved toxicity Grade 2 or more according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) from previous anticancer therapy;
5. Need for transfusion within 14 days prior to the first dose of trial treatment;
6. Prior chemotherapy, biological therapy, radiation therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment;
7. Inadequate hematological, liver, renal, cardiac function; 8. Prior treatment with other agents targeting the HGF/c-Met pathway; 9. Past or current history of neoplasm other than 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 (for a full list of exlustion criteria please see the study protocol).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified