| General information |
| Database: | DB00299 |
| Objective: | Integrins are involved in tumour progression and metastasis, and differentially expressed on colorectal cancer (CRC) cells. Abituzumab (EMD 525797), a humanised monoclonal antibody targeting integrin ¦Á¦Í heterodimers, has demonstrated preclinical activity. This trial was designed to assess the tolerability of different doses of abituzumab in combination with cetuximab and irinotecan (phase I) and explore the efficacy and tolerability of the combination versus that of cetuximab and irinotecan in patients with metastatic CRC (mCRC) (phase II part). |
| Authors: | ¨¦lez E, et al |
| Title: | Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wildtype metastatic colorectal cancer: the randomisedphase I/II POSEIDON trial. |
| Journal: | Ann Oncol. |
| Year: | 2015 |
| PMID: | 25319061 |
| Trial Design |
| Clinical Trial Id: | NCT01008475 |
| Agent: | abituzumab
|
| Target: | Integrin alphaV
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | KRAS wildtype metastatic colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Abituzumab+cetuximab + irinotecan |
| Study Type: | a randomisedphase I/II POSEIDON trial |
| Key Patients Feature: | Adults aged more than and equal to 18 years with histologically confirmed KRAS exon 2 wildtype mCRC, documented distant metastases and at least one radiographically documented measurable lesion in a previously nonirradiated area were eligible. |
| Biomarker: | KRAS (exon 2) wildtype |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | cetuximab+irinotecan alone |
| Treatment Info: | The trial comprised an initial safety runin using abituzumab doses up to 1000 mg combined with a standard of care (SoC: cetuximab plus irinotecan) and a phase II part in which patients were randomised 1 : 1 : 1 to receive abituzumab 500 mg (arm A) or 1000 mg (arm B) every 2 weeks combined with SoC, or SoC alone (arm C). |
| Primary End Point: | investigatorassessed progression free survival (PFS). |
| Secondary End Point: | overall survival (OS), response rate (RR) and tolerability. Associations between tumour integrin expression and outcomes were also assessed. |
| Patients Number: | 16(phase I); 216(phase II) |
| Trial Results |
| DLT_MTD: | Phase I showed that abituzumab doses up to 1000 mg were well tolerated in combination with SoC. |
| Objective Response Rate: | RRs were also similar. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS was similar in the three arms: arm A versus SoC, hazard ratio (HR) 1.13 [95% confidence interval (CI) 0.781.64]; arm B versus SoC, HR 1.11 (95% CI 0.771.61). |
| Median OS A vs. C: | A trend toward improved OS was observed: arm A versus SoC, HR 0.83 (95% CI 0.541.28); arm B versus SoC, HR 0.80 (95% CI 0.521.25). High tumour integrin ¦Áv¦Â6 expression was associated with longer OS in arms A [HR 0.55 (0.301.00)] and B [HR 0.41 (0.210.81)] than in arm C. |
| Adverse Event(agent arm): | Grade more than and equal to 3 treatmentemergent adverse events were observed in 72%, 78% and 67% of patients. |
| Conclusions: | The primary PFS end point was not met, although predefined exploratory biomarker analyses identified subgroups of patients in whom abituzumab may have benefit. The tolerability of abituzumab combined with cetuximab and irinotecan was acceptable. Further study is warranted. |