Table 1.
Study design summary
| Study number | 001 (NCT01014936) [11] | 003 (NCT01832506) [12] | 004 (NCT01988493) [17] | 005 (NCT02115373) [18] | 007 (EudraCT 2013–003226-86) [19] | VISION; 022 (NCT02864992) [6] |
|---|---|---|---|---|---|---|
| Title | A phase 1 open label, non-randomized, dose-escalation first-in-man trial to investigate the c-Met kinase inhibitor MSC2156119J under three different regimens in subjects with advanced solid tumors | A Japanese multicenter, open label, phase 1 trial of c-Met inhibitor MSC2156119J given orally as monotherapy to subjects with solid tumors | A multicenter, randomized, phase 1b/2 trial to evaluate the efficacy, safety, and PK of MSC2156119J as monotherapy versus sorafenib in Asian subjects with MET + advanced hepatocellular carcinoma and Child–Pugh class A liver function | A multicenter, single-arm, phase 1b/2 study to evaluate efficacy, safety, and PK of MSC2156119J as monotherapy in subjects with MET + advanced hepatocellular carcinoma with Child Pugh class A liver function who have failed sorafenib treatment | A phase 1, pen label, three-part, single-center trial to investigate the absolute and relative bioavailability, mass balance, and metabolite profile of MSC2156119J in healthy male subjects | A phase 2 single-arm trial to investigate tepotinib in advanced (locally advanced or metastatic) non-small cell lung cancer with MET exon 14 (METex14) skipping alterations or MET amplification (VISION) |
| Methodology and study design | Phase 1, multicenter, open label, non-randomized, sequential and parallel group study | Phase 1, multicenter, open label, non-randomized, sequential group study | Phase 1b/2 multicenter, open label, single arm (phase 1b) and randomized, active-controlled (phase 2) study | Phase 1b/2 multicenter, open label, single-arm study | Phase 1, single-center, open label, parallel group study | Phase 2 multicenter, open label, single-arm study |
| Participants | 149 adult patients with advanced solid tumors | 12 Japanese adult patients with solid tumors | 72 Asian, adult patients with advanced HCC and Child–Pugh class A liver function treated with tepotinib | 66 adult patients with advanced HCC and Child–Pugh class A liver function | 27 healthy participants | 206 adult patients with advanced (stage IIIB/IV) NSCLC with MET exon 14 skipping alterations or MET amplification |
| Tepotinib treatment | Tepotinib doses of 30 mg to 1400 mg/day in three different treatment regimens (QD, 2 weeks on - 1 week off, TIW) | Tepotinib 215, 300, or 500 mg/day QD | Tepotinib 300, 500, 1000 mg/day QD | Tepotinib 300 or 500 mg/day QD | Tepotinib 100 mg or 500 mg single dose | Tepotinib 500 mg/day QD over 21-day cycle(s) until disease progression or undue toxicity |
| Number of patients and events included in present analyses | ||||||
| Efficacy | ||||||
| Overall | 0 | 0 | 0 | 0 | 0 | 152 |
| OR | 0 | 0 | 0 | 0 | 0 | 146 |
| DOR | 0 | 0 | 0 | 0 | 0 | 66 |
| PFS | 0 | 0 | 0 | 0 | 0 | 146 |
| Safety | ||||||
| Number of participants in analysis set | 149 | 12 | 72 | 66 | 27 | 206 |
| Edema event | ||||||
| Patients | 33 | 4 | 32 | 40 | 0 | 130 |
| Observations | 48 | 4 | 60 | 71 | 0 | 313 |
| Serum albumin evaluation | ||||||
| Patients | 149 | 12 | 72 | 64 | 0 | 201 |
| Observations | 1716 | 153 | 804 | 648 | 0 | 2015 |
| Serum creatinine evaluation | ||||||
| Patients | 149 | 12 | 72 | 65 | 11a | 201 |
| Observations | 1739 | 153 | 825 | 745 | 56 | 2068 |
| QTcF interval | ||||||
| Patients | 144 | 12 | 70 | 59 | 0 | 107 |
| Observations | 953 | 91 | 568 | 504 | 0 | 1083 |
DOR, duration of response; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer; OR, objective response; PFS, progression-free survival; PK, pharmacokinetics; QD, once daily; QTcF, QT interval corrected using Fredericia’s formula; TIW, three times a week
aSerial-sampled serum creatinine data from study 007 were used to illustrate the time-profile of serum creatinine