c-Met Second-Line Hepatocellular Carcinoma

NCT02115373 | Completed Phase 1 Results

• 2 other identifiers: EMR 200095_0052013-002053-30
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1b/2, multicenter, single arm trial to assess the efficacy, safety, and pharmacokinetics (PK) of MSC2156119J as monotherapy in subjects with MET+ advanced hepatocellular carcinoma (HCC) with child Pugh Class A liver function who have failed sorafenib treatment.

Conditions

Carcinoma, Hepatocellular

Keywords

Hepatocellular Carcinoma; c-Met inhibitor; Phase 1b; Sorafenib; MSC2156119J

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Number of Participants Experiencing Dose Limiting Toxicity (DLT) According to National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) for Adverse Events (AEs) Version 4.0

  DLT: defined using NCI-CTCAE for AEs Version 4.0, as any of following toxicities: Grade 4 neutropenia for more than 7 days; greater than or equal to (\>=) Grade 3 febrile neutropenia for more than 1 day; Grade 4 or Grade 3 thrombocytopenia with nontraumatic bleeding; \>=Grade 3 uncontrolled nausea/vomiting and/or diarrhoea despite adequate treatment for more than 3 days; \>=Grade 3 any non-hematological AE. (DLT defined specifically for following cases: \>=Grade 3 liver AE requiring recovery period of more than 7 days or to Grade 1 or less or Grade 2 with liver metastases ; \>=Grade 3 lipase and/or amylase elevation with confirmation of pancreatitis. An isolated lipase and/or amylase elevation of \>=Grade 3 without clinical/radiological evidence of pancreatitis was not classified as DLT); and AEs assessed by investigators to be exclusively related to the participant's underlying disease or medical condition/concomitant treatment are not considered as DLTs.

  Day 1 to Day 21 of Cycle 1 (each cycle was 21 days)

• Phase 2: Number of Participants Who Were Progression-free at 12 Weeks (PFS Status) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  PFS status was evaluated by the number of participants who were progression-free at 12 weeks according to RECIST Version 1.1. Participants were considered to be progression-free if the participant had a tumor assessment of Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 millimeter (mm). Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters, or Stable Disease (SD) defined as any cases that do not qualify for either partial response or progressive disease (an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started)12 weeks after start of treatment or later.

  At 12 weeks post first-dose in Phase 2

Secondary Outcomes (25)

• Phase 1b and Phase 2: Time to Progression According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Time from first study drug administration to the date of first occurrence of radiological progressive disease (PD), assessed up to 12 months after last participant's first dose (assessed maximum up to 1369 days)

• Phase 1b and Phase 2: Progression-free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  From randomization up to first observation of PD or death, assessed maximum up to 1369 days

• Phase 1b and Phase 2: Progression-free Survival (PFS) Time According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for Hepatocellular Carcinoma (HCC)

  From randomization up to first observation of PD or death, assessed maximum up to 1369 days

• Phase 2: Time-to-symptomatic Progression (TTSP)

  From date of randomization up to 1369 days

• Phase 1b and Phase 2: Overall Survival (OS) Time

  From date of randomization up to the date of death, assessed maximum up to 1369 days

Study Arms (3)

Phase 1b: Tepotinib 300 mg

EXPERIMENTAL

Drug: Tepotinib

Phase 1b: Tepotinib 500 mg

EXPERIMENTAL

Drug: Tepotinib

Phase 2: Tepotinib 500 mg

EXPERIMENTAL

Drug: Tepotinib

Interventions

Tepotinib DRUG

Participants received a single oral dose of Tepotinib 300 milligram (mg) in each 21 days treatment cycle until progressive disease, intolerable toxicity, death, or withdrawal from treatment.

Also known as: MSC2156119J

Phase 1b: Tepotinib 300 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed HCC
• Child Pugh Class A liver function score
• For Phase 2 only: MET+ status
• Male or female, 18 years of age or older
• Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (inclusive)
• Availability of a pretreatment tumor biopsy (excluding fine needle aspiration and cytology samples) taken after the subject has discontinued sorafenib and within 28 days before the day of first dosing with MSC2156119J. From the pretreatment biopsy either a formalin-fixed (formalin fixation is mandatory) paraffin-embedded block with tumor tissue (preferred) or at least 15 unstained slides must be sent to the central laboratory prior to enrollment. An associated pathology report must also be sent with the sample
• Previously treated with sorafenib for greater than or equal to 4 weeks and discontinued sorafenib treatment at least 14 days prior to Day 1 due to either intolerance or radiographic progression
• Signed and dated informed consent indicating that the subject (or legally acceptable representative if applicable by local laws) has been informed of all the pertinent aspects of the trial prior to enrollment
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures
• Life expectancy of at least 3 months as judged by the investigator

You may not qualify if:

• Prior treatment with any agent targeting the hepatocyte growth factor (HGF)/c-Met pathway
• Local-regional therapy within 4 weeks before Day 1
• Impaired cardiac function

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Please contact the Merck KGaA Communication Center located in

Darmstadt, Germany

Location

Related Publications (2)

• Xiong W, Hietala SF, Nyberg J, Papasouliotis O, Johne A, Berghoff K, Goteti K, Dong J, Girard P, Venkatakrishnan K, Strotmann R. Exposure-response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations. Cancer Chemother Pharmacol. 2022 Jul;90(1):53-69. doi: 10.1007/s00280-022-04441-3. Epub 2022 Jun 30.

  PMID: 35771259 DERIVED

• Decaens T, Barone C, Assenat E, Wermke M, Fasolo A, Merle P, Blanc JF, Grando V, Iacobellis A, Villa E, Trojan J, Straub J, Bruns R, Berghoff K, Scheele J, Raymond E, Faivre S. Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression. Br J Cancer. 2021 Jul;125(2):190-199. doi: 10.1038/s41416-021-01334-9. Epub 2021 Apr 6.

  PMID: 33824476 DERIVED

Related Links

• : Redacted Clinical study report, redacted clinical study protocol and redacted statistical analysis plan for this study is also available at the HC-PRCI portal (Health Canada-Public release of clinical information)

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tepotinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 16, 2014
• Study Start: May 18, 2014
• Primary Completion: February 14, 2018
• Study Completion: February 14, 2018
• Last Updated: August 24, 2022
• Results First Posted: August 9, 2019

Record last verified: 2022-08

Locations

DE (1)