| General information |
| Database: | DB00134 |
| Objective: | This dose escalation study evaluated INC280 in patients (pts) with MET dependent advanced solid tumors |
| Authors: | Novartis Pharmaceuticals |
| Title: | Phase I study of the safety and efficacy of INC280 in patients with advanced METdependent solid tumors. |
| Journal: | meeting abstract |
| Year: | 2014 ASCO Annual Meeting |
| PMID: | http://meetinglibrary.asco.org/content/128427144 |
| Trial Design |
| Clinical Trial Id: | NCT01324479. |
| Agent: | INC280
|
| 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: | Eligible pts (aged more than and equal to 18 years, ECOG PS less than and equal to 2) had tumors that were refractory to current therapy or for which no effective therapy exists, and confirmed MET dysregulation (by FISH or IHC).(79% male, median age 57 years, 61% PS 0). |
| Biomarker: | MET dysregulation (by FISH or IHC). |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | An adaptive Bayesian logistic regression model guided dose escalation in establishing the MTD/RP2D. |
| Primary End Point: | the MTD or recommended Ph II dose (RP2D), safety and tolerability of INC280; |
| Secondary End Point: | preliminary antitumor activity and PK. |
| Patients Number: | 33 |
| Trial Results |
| DLT_MTD: | DLTs occurred at 200 mg BID, 250 mg BID and 450 mg BID (1 pt each). DLTs were Gr 3 fatigue (2 pts), and Gr 3 serum bilirubin increased. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Stable disease was reported in 8/33 (24%) heavily pretreated pts. Paired biopsy data showed nearcomplete phosphoMET shutdown in a colorectal cancer pt at 450 mg BID. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most frequent drugrelated AEs (any grade [Gr]) were decreased appetite (33%), nausea (30%), vomiting (27%), and fatigue (27%). The most common drugrelated Gr 3/4 AEs were fatigue (9%), and decreased appetite (6%). |
| Conclusions: | Oral INC280 BID is well tolerated, and the RP2D is 600 mg BID. Dose expansion is ongoing in pts with non small cell lung cancer, hepatocellular carcinoma, and other tumors. These results suggest INC280 should be further evaluated, and Ph II studies in various solid tumors are ongoing. |