| General information |
| Database: | DB00135 |
| Objective: | Results of the firstinhumanphase I trial assessing MSC2156119J in patients (pts) with advanced solid tumors. |
| Authors: | Gerald Steven Falchook, et al |
| Title: | Results of the firstinhumanphase I trial assessing MSC2156119J in patients (pts) with advanced solid tumors. |
| Journal: | J Clin Oncol |
| Year: | 2014 ASCO Annual Meeting |
| PMID: | http://meeting.ascopubs.org/cgi/content/abstract/32/15_suppl/2521 |
| Trial Design |
| Clinical Trial Id: | NCT01014936 |
| Agent: | MSC2156119J
|
| Target: | Hepatocyte growth factor receptor
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase I study |
| Key Patients Feature: | patients (pts) with advanced solid tumors |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Pts received 1x/d oral MSC2156119J (21d cycles; 3 regimens [R]): d1-14 follotheyd by 7d rest (R1); 3x/wk (R2); or d1-21 (R3). An optimized formulation (OF) was introduced in Aug 2011. |
| Primary End Point: | MTD; |
| Secondary End Point: | antitumor activity, safety, pharmacokinetics (PK), and pharmacodynamics (Pd). |
| Patients Number: | 126 |
| Trial Results |
| DLT_MTD: | Six pts reported doselimiting toxicities: asymptomatic G4 lipase and G3 amylase increase (R1; 115 mg/d), G3 nausea and vomiting (R2; 130 mg/d; OF), asymptomatic G3 lipase increase (R2; 60 + 100 mg/d; OF), G3 fatigue (R3; 1400 mg/d; OF), and G3 ALT elevation (R3; 1000 mg/d; OF). |
| Objective Response Rate: | NA |
| Disease Control Rate: | Pre and ontherapy tumor biopsies showed phosphocMet inhibition in 19/21 evaluable pts. One pt (esophageal adenocarcinoma) had confirmed partial response (PR); 2 pts (nasopharyngeal and colorectal carcinoma) had unconfirmed PRs. Stable disease (SD) more than and equal to 4 mo was seen in 18 pts, incl. 1 pt with SD >32 mo. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Other more than and equal to G3 treatmentrelated adverse events (trAEs) were G3 peripheral edema (1 pt; R3; 300 mg/d; OF) and G3 AST elevation (1 pt; R3; 1000 mg/d; OF). Most frequent G2 trAEs (R1-3): fatigue (n=8), peripheral edema (n=3), vomiting (n=3), nausea (n=2), asymptomatic lipase increase (n=2), and neutropenia (n=2). 79% of pts had no trAE >G1 |
| Conclusions: | MSC2156119J was well tolerated and showed antitumor activity. Recommendedphase II dose (RP2D) is 500 mg 1xd. Dose escalation was stopped at 2.8xRP2D (1400 mgd). An MTD was not reached. Additional Pd and biomarker data (cMet status by immunohistochemistry [IHC] and in situ hybridization) will be presented. |