Clinical Trials

Date: 2017-01-23

Type of information: Presentation of results at a congress

phase: 3

Announcement: ppresentation of results at the 2016 Gastrointestinal Cancers Symposium (GICS)

Company: Amgen (USA - CA)

Product: Vectibix® (panitumumab)

Action mechanism: monoclonal antibody. Vectibix® (panitumumab) is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). EGFR is a transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine kinases, including EGFR, HER2, HER3, and HER4. EGFR is constitutively expressed in normal epithelial tissues, including the skin and hair follicle. EGFR is overexpressed in certain human cancers, including colon and rectum cancers. Interaction of EGFR with its normal ligands (eg, EGF, transforming growth factor-alpha) leads to phosphorylation and activation of a series of intracellular proteins, which in turn regulate transcription of genes involved with cellular growth and survival, motility, and proliferation. Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR.

Disease: chemorefractory wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC)/p>

Therapeutic area: Cancer - Oncology

Country: Brazil, Canada, Chile, China, Croatia, Estonia, Greece, India, Republic of Korea, Latvia, Lithuania, Malaysia, Mexico, Philippines, Romania, Serbia

Trial details:

• Study '0007 is a Phase 3 global, multicenter, randomized, open-label study. The study  was designed to evaluate the survival benefit of Vectibix® and best supportive care (BSC) compared to BSC alone in patients with chemorefractory wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC). The primary endpoint was overall survival (OS). Key secondary endpoints included progression-free survival (PFS) in patients with wild-type KRAS mCRC, as well as OS and PFS in patients with wild-type RAS (absence of mutations in exons 2, 3 and 4 of KRAS and NRAS) mCRC. Patients were randomized 1:1 to receive 6 mg/kg of Vectibix every 14 days and BSC, or BSC alone (as defined by the investigator).
• There were a total of 377 patients enrolled: 324 out of 377 subjects with RAS mutation status determined (86 percent ascertainment rate) Out of 324, 270 had wild-type RAS (83 percent), 54 were found to be mutant RAS (17 percent) 189 patients for KRAS (exon 2) group for Vectibix and BSC (NCT01412957)

Latest news:

• • On January 23, 2016, Amgen announced the presentation of detailed results of a Phase 3 study with Vectibix® (panitumumab) and best supportive care (BSC) compared to BSC alone. The study met its primary endpoint, demonstrating a statistically significant improvement in overall survival (OS) in patients with chemorefractory wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC; n=377 total). This is the first Phase 3 Vectibix study to include an analysis of efficacy of Vectibix by wild-type KRAS (exon 2) and in wild-type RAS tumor mutation status in its primary analysis, providing important information about OS in these populations. These results, in addition to secondary endpoint data, were presented at the 2016 Gastrointestinal Cancers Symposium (GICS) in San Francisco .
• The study (GICS abstract #642) showed that patients with wild-type KRAS (exon 2) mCRC treated with Vectibix®  and BSC achieved a median OS of 10 months compared to 7.4 months for patients treated with BSC alone (hazard ratio [HR]=0.73, 95 percent confidence interval [CI]=0.57-0.93, p=0.0096). Data from a key secondary endpoint showed that patients with wild-type RAS (absence of mutations in exons 2, 3 and 4 of KRAS and NRAS) mCRC treated with Vectibix®  and BSC achieved a median OS of 10 months compared to 6.9 months for patients treated with BSC alone (n=270; HR=0.70, 95 percent CI=0.53-0.93, p=0.0135). Patients with mutant RAS mCRC did not benefit from Vectibix® treatment (n=54; OS HR=0.99, 95 percent CI=0.49-2.00). The safety profile was comparable to the known safety profile of Vectibix®  when administered as a single agent, with skin, nail, gastrointestinal and electrolyte disorders being the most frequently reported adverse events.
• Treatment with Vectibix® combined with BSC in patients with wild-type KRAS resulted in median PFS of 3.6 months versus 1.7 months with BSC alone (HR=0.51, 95 percent CI=0.41-0.64, p=0.0001). In patients with wild-type RAS, the Vectibix combination resulted in median PFS of 5.2 months versus 1.7 months with BSC alone (HR=0.46, 95 percent CI=0.35-0.59, p=0.0001).
• For patients with wild-type KRAS, ORRs were 27.0 percent with Vectibix versus 1.6 percent with BSC (HR=24.9, 95 percent CI=7.5-123.8, p<0.0001). For patients with wild-type RAS, ORRs were 31.0 percent with Vectibix® versus 2.3 percent for BSC (ODDS Ratio=20.0, 95 percent CI=5.9-101.6, p<0.0001).
• Patients with mutant RAS mCRC did not benefit from Vectibix® treatment (OS HR=0.99, 95 percent CI=0.49-2.00). No new safety signals were seen in this study. The safety profile was comparable to the known safety profile of Vectibix® when administered as a single agent, with skin, nail, gastrointestinal and electrolyte disorders being the most frequently reported adverse events.
• • On June 18, 2015, Amgen announced that a Phase 3 study evaluating Vectibix® (panitumumab) and best supportive care (BSC) met its primary endpoint, demonstrating a statistically significant improvement in overall survival (OS) in patients with chemorefractory wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC) compared to those patients treated with BSC alone. The Vectibix treatment arm further showed statistical significance for all key secondary endpoints including OS in patients with wild-type RAS (absence of mutations in exons 2, 3 and 4 of KRAS and NRAS) mCRC. In the Vectibix treatment arm, the observed adverse events were consistent with the known Vectibix safety profile. Full results will be submitted to a future medical congress and for publication.

Is general: Yes