A Japanese Phase 1 Trial of c-Met Inhibitor MSC2156119J in Subjects With Solid Tumors

NCT01832506 | Completed Phase 1 Results

• 1 other identifier: EMR 200095-003
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Japanese multicenter, open-label, Phase 1 study to evaluate safety and efficacy of MSC2156119J in subjects with malignant solid tumor which is refractory to standard therapy or to which no effective standard therapy is applicable.

Conditions

Solid Tumors

Keywords

Solid Tumors; MSC2156119J; c-Met inhibitor; Japanese; Phase 1

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Experiencing Dose Limiting Toxicity (DLT)

  DLT: defined using National Cancer Institute Common Toxicity Criteria for Adverse Events 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; Grade 4 or Grade 3 thrombocytopenia with bleeding; \>=Grade 3 nausea despite adequate treatment; \>=Grade 3 any non-hematological AE (DLT defined specifically for following cases: \>=Grade 3 liver adverse event \[AE\] requiring recovery period of more than 7 days or to Grade 1 without liver metastases 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 \>=Grade 2 any AE not otherwise defined as DLT that, due to prolonged recovery to Grade 1 (or less) or baseline status, led to delay of treatment with IMP for more than 21 days.

  Cycle 1 (Day 1 up to 21)

Secondary Outcomes (15)

• Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs or TEAEs Leading To Death

  Baseline Up to 30 days after last dose of study drug administration (55.1 weeks)

• Number of Subjects With Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score of 2 or Higher

  Baseline up to 30 days after last dose of study drug administration (55.1 weeks)

• Maximum Plasma Concentration (Cmax) After Single Dose of MSC2156119J

  pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

• Maximum Plasma Concentration (Cmax) After Multiple Dose of MSC2156119J

  pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 14 Cycle 1

• Time to Reach Maximum Plasma Concentration (Tmax) After Single Dose of MSC2156119J

  pre-dose, 0.25, 0.5, 1, 2, 4, 8, 10, 24 hours post-dose on Day 1 Cycle 1

Study Arms (1)

MSC2156119J

EXPERIMENTAL

Drug: MSC2156119J

Interventions

MSC2156119J DRUG

Subjects will be administered with MSC2156119J 215 mg, 300 mg and 500 mg orally once daily for repeated 21-day cycles until disease progression or unacceptable toxicity.

MSC2156119J

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject with a histologically or cytologically confirmed diagnosis of malignant solid tumor which is refractory to standard therapy or to which no effective standard therapy is applicable
• An archived tumor tissue is available or biopsy of tumor tissues can be newly performed
• A Japanese male or female, age greater than or equal to (\>=) 20 years
• A subject who has read the Subject Information Sheet and understood the details of this clinical trial, and is willing and able to give his/her informed consent.
• A female of child-bearing potential must have a negative blood pregnancy test result at her screening period. A female subject of child-bearing potential must be willing to avoid pregnancy by using an adequate method of contraception Life expectancy is at least 3 months

You may not qualify if:

• Known Human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B
• Presence of liver fibrosis or liver cirrhosis that has been histologically diagnosed
• Signs or symptoms that suggest transmissible spongiform encephalopathy
• Received major surgery within 6 weeks before Day 1 in Cycle 1
• Known drug abuse or alcohol abuse
• Known hypersensitivity to any of the trial treatment ingredients
• Hematological test abnormalities
• Renal impairment as defined in the protocol
• Liver dysfunction as defined in the protocol
• History or presence of central nervous system metastasis
• History or presence of disease or condition that may hamper compliance or absorption of the investigational medicinal product (IMP) due to difficulty in swallowing or absorption
• Poor performance status of Eastern Cooperative Oncology Group Performance status (ECOG PS) \>= 2
• Received any anti-cancer therapy days Received extensive prior radiotherapy that irradiates more than 30 percent of bone marrow
• Received any radiotherapy within 4 weeks before Day 1 in Cycle 1
• Pregnancy and lactation period

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (2)

Research site

Kashiwa, Japan

Location

Research site

Shizuoka, Japan

Location

Related Publications (2)

• Shitara K, Yamazaki K, Tsushima T, Naito T, Matsubara N, Watanabe M, Sarholz B, Johne A, Doi T. Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors. Jpn J Clin Oncol. 2020 Aug 4;50(8):859-866. doi: 10.1093/jjco/hyaa042.

  PMID: 32328660 RESULT

• 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

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Serono Co., Ltd., Japan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2013
• First Posted: April 16, 2013
• Study Start: April 30, 2013
• Primary Completion: March 31, 2014
• Study Completion: October 31, 2014
• Last Updated: August 6, 2020
• Results First Posted: December 7, 2016

Record last verified: 2020-07

Locations

JP (2)