Phase 2
N=66
c-Met Second-Line Hepatocellular Carcinoma
Carcinoma, Hepatocellular
Bottom Line
View on ClinicalTrials.gov: NCT02115373 ↗Enrolled (actual)
66
Serious AEs
42.4%
Results posted
Aug 2019
Primary outcome: Primary: 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 — 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Tepotinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck KGaA, Darmstadt, Germany
- Primary completion
- Feb 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
0; 0 | — |
| PRIMARY 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 |
31 | — |
| SECONDARY Phase 1b and Phase 2: Time to Progression According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
3; 9; 36 | — |
| SECONDARY Phase 1b and Phase 2: Progression-free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
4; 12; 38 | — |
| SECONDARY Phase 1b and Phase 2: Progression-free Survival (PFS) Time According to Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for Hepatocellular Carcinoma (HCC) |
4; 9; 37 | — |
| SECONDARY Phase 2: Time-to-symptomatic Progression (TTSP) |
4.86 | — |
| SECONDARY Phase 1b and Phase 2: Overall Survival (OS) Time |
3; 11; 40 | — |
| SECONDARY Phase 1b and Phase 2: Percentage of Participants With Best Overall Tumor Assessment of CR or PR According to RECIST v1.1 |
50.0; 0.0; 8.2 | — |
| SECONDARY Phase 1b and Phase 2: Percentage of Participants With Disease Control |
50.0; 30.8; 57.1 | — |
| SECONDARY Phase 1b and Phase 2: Percentage of Participants With Biological Response |
66.7; 45.5; 31.1 | — |
| SECONDARY Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Tepotinib |
4440; 5060; 15200; 12900 | — |
| SECONDARY Phase 1b: Dose Normalized Area Under the Plasma Concentration-Time Curve From Zero to Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Tepotinib |
14.8; 10.1; 50.7; 25.8 | — |
| SECONDARY Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tepotinib |
NA; NA; NA; NA | — |
| SECONDARY Phase 1b: Maximum Observed Plasma Concentration (Cmax) of Tepotinib |
261; 278; 734; 677 | — |
| SECONDARY Phase 1b: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of Tepotinib |
0.871; 0.556; 2.45; 1.35 | — |
| SECONDARY Phase 1b: Minimum Observed Plasma Concentration (Cmin) of Tepotinib |
526; 435 | — |
| SECONDARY Phase 1b: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib |
10.0; 8.0; 8.0; 6.1 | — |
| SECONDARY Phase 1b: Average Plasma Concentration at Steady State (Cav) of Tepotinib |
635; 542 | — |
| SECONDARY Phase 1b: Apparent Total Body Clearance From Plasma (CL/f) of Tepotinib |
17.7; 34.9 | — |
| SECONDARY Phase 1b: Apparent Volume of Distribution During the Terminal Phase (Vz/f) of Tepotinib |
NA; NA; NA; NA | — |
| SECONDARY Phase 1b: Apparent Volume of Distribution During the Steady State (Vss/f) of Tepotinib |
NA; NA; NA; NA | — |
| SECONDARY Phase 1b: Apparent Terminal Elimination Rate Constant (λz) of Tepotinib |
NA; NA; NA; NA | — |
| SECONDARY Phase 1b: Apparent Terminal Half-life (t1/2) of Tepotinib |
NA; NA; NA; NA | — |
| SECONDARY Phase 1b: Time Prior to the First Quantifiable (Non-zero) Concentration (Tlag) of Tepotinib |
0.53; 0.50 | — |
| SECONDARY Phase 1b: Percentage Peak-Trough Fluctuation (PTF) Post First Dose of Tepotinib |
31.5; 35.9 | — |
| SECONDARY Phase 1b: Accumulation Ratio of Cmax (Racc (Cmax)) |
2.81; 2.32 | — |
| SECONDARY Phase 1b: Accumulation Ratio of AUC (Racc (AUC) |
3.43; 2.51 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- Prior systemic anticancer treatment for advanced HCC (except for sorafenib as described in the inclusion criteria)
- 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
- Other protocol defined exclusion criteria could apply
Data sourced from ClinicalTrials.gov (NCT02115373). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.