| General information |
| Database: | DB00304 |
| Objective: | Panitumumab, a fully human antiepidermal growth factor receptor monoclonal antibody (mAb), has demonstrated efficacy in patients with wildtype KRAS metastatic colorectal cancer (mCRC). Rilotumumab and ganitumab are investigational, fully human mAbs against hepatocyte growth factor (HGF)/scatter factor and IGF1R, respectively. Here they evaluate combining rilotumumab or ganitumab with panitumumab in previously treated patients with wildtype KRAS mCRC. |
| Authors: | Van Cutsem E, et al |
| Title: | Randomizedphase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wildtype KRAS metastatic colorectal cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2014 |
| PMID: | 24919569 |
| Trial Design |
| Clinical Trial Id: | NCT00788957 |
| Agent: | panitumumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | KRAS wildtype metastatic colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | rilotumumab/ganitumab+panitumumab |
| Study Type: | an exploratory, global, multicenter IIIpartphase Ib/II trial |
| Key Patients Feature: | Eligible patients were more than and equal to 18 years of age, had an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1, and had histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum. Radiographic evidence of disease progression during or following prior treatment with irinotecan and/or oxaliplatinbased chemotherapy for mCRC was required. At least 1 unidimensionally measurable lesion per modified RECIST 1.0 was required. Archival tumor tissue was confirmed by a central laboratory to be WT KRAS using a validated test method. |
| Biomarker: | wildtype KRAS; MET and IGFrelated protein expression |
| Biomark Analysis: | Exploratory biomarker analyses, including MET and IGFrelated protein expression, failed to indicate conclusive predictive evidence on efficacy endpoints. |
| Control Group Info: | panitumumab alone |
| Treatment Info: | Part 1 was a phase Ib dosefinding study of panitumumab plus rilotumumab. Part 2 was a randomizedphase II trial of panitumumab in combination with rilotumumab, ganitumab, or placebo. Archival tissue specimens were collected for exploratory correlative work. |
| Primary End Point: | Part 1: the incidence of doselimiting toxicities (DLT). Part 2: objective response rate (ORR); |
| Secondary End Point: | safety, progression free survival (PFS), and overall survival (OS) |
| Patients Number: | 11(part 1); 142(part 2) |
| Trial Results |
| DLT_MTD: | In part 1, no DLTs were reported. A recommendedphase II dose of 10 mg/kg rilotumumab was selected. |
| Objective Response Rate: | for the panitumumab plus rilotumumab (n = 48), panitumumab plus ganitumab (n = 46), and panitumumab plus placebo arms (n = 48), the ORRs were 31%, 22%, and 21%, respectively. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median PFS was 5.2, 5.3, and 3.7 months |
| Median OS A vs. C: | median OS 13.8, 10.6, and 11.6 months |
| Adverse Event(agent arm): | Adverse events were tolerable. |
| Conclusions: | Panitumumab plus rilotumumab met the prespecified criterion for improvement in ORR whereas ganitumab did not. This is the first study to suggest a benefit for combining an HGF inhibitor (rilotumumab) with panitumumab in previously treated patients with wildtype KRAS mCRC. |