Amgen announces the results for Phase 3 PRIME '203' trial of Vectibix

Amgen (Nasdaq: AMGN) today announced that the Phase 3 PRIME "203" trial evaluating Vectibix® (panitumumab) administered in combination with FOLFOX (an oxaliplatin-based chemotherapy) as a first-line treatment of metastatic colorectal cancer (mCRC) failed to meet a secondary endpoint of overall survival. Earlier this year, it was announced that the trial met its primary endpoint by significantly prolonging progression-free survival (PFS) in the first-line treatment of patients with KRAS wild-type mCRC.

The prospective analysis of the 203 study showed that Vectibix, when added to a FOLFOX chemotherapy regimen in patients with KRAS wild-type mCRC, resulted in a median overall survival of 23.9 months compared to 19.7 months for patients treated with FOLFOX alone. The median overall survival difference of 4.2 months in the Vectibix arm did not reach statistical significance>

"As we previously announced, the 203 study met its primary endpoint of progression-free survival in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "While not statistically significant, we are also encouraged by the positive trend of the data for overall survival for these patients treated with Vectibix."

Overall survival appeared to be reduced in patients with KRAS mutant tumors receiving Vectibix. Although not statistically significant, this result emphasizes the importance, as described in product labeling, of ensuring that patients receiving Vectibix( )do not bear tumors containing KRAS mutations.

Overall, the adverse event profile was as anticipated for an anti-EGFR antibody in combination with oxaliplatin-based chemotherapy, including known events such as rash, diarrhea and hypomagnesemia. Vectibix-related grade 3 infusion reactions were reported for two patients (less than 1 percent).

Originally designed to compare the treatment effect in the overall population, the study was amended to analyze outcomes with respect to the presence or absence of activating mutations in KRAS in the tumor itself. Tumor KRAS status was ascertained in more than 90 percent of the 1,183 patients enrolled in the trial.

Available results from the trial were presented earlier this year at the 2009 ECCO 15 - ESMO 34 European Multidisciplinary Congress in Berlin, Germany showing that Vectibix significantly improved median progression-free survival by 1.6 months (9.6 versus 8.0 months for patients treated with FOLFOX alone, in patients with KRAS wild-type mCRC (primary endpoint). Further, the addition of Vectibix to chemotherapy also improved response rate in the KRAS wild-type patient population as measured by blinded central review (55 percent versus 48 percent in the FOLFOX only arm).

The data for the 203 study has been submitted for consideration of presentation at the American Society of Clinical Oncology - The Gastrointestinal Cancers Symposium Meeting for 2010.

Study Design

Patients enrolled in the "203" or PRIME trial (Panitumumab Randomized trial in combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy) were randomized to receive either 6.0 mg/kg of Vectibix and FOLFOX4 once every two weeks (Q2W) or FOLFOX4 alone Q2W. The primary endpoint of the study is progression-free survival by KRAS status and secondary endpoints include overall survival, objective response rate, time to progression, duration of response and safety.