Regulatory Decision Summary for Vectibix

To support the proposed refinement of the indicated patient population of the monotherapy, a pivotal study 20100007, a phase III, open label, randomized trial in subjects with chemorefractory wild-type KRAS mCRC, was submitted. Data showed that Vectibix plus best supportive care (BSC) provides superior survival benefit (overall survival, OS) versus BSC alone among patients with wild-type RAS, indicating a reduction in the risk of death of 41% (hazard ratio HR: 0.594, 95% CI: 0.440-0.803). The absolute difference in median OS was 3.1 months between the Vectibix plus BSC arm and the BSC alone arm (10.0 months vs. 6.9 months). In contrast, among patients with mutant RAS, no treatment benefit was indicated for Vectibix plus BSC (OS HR: 0.985, 95% CI: 0.485-1.999).

In terms of safety, a higher incidence of treatment emergent adverse events (TEAE) of any grade (61.7% vs. 97.2%) and of Grade 3 and 4 (18.7% vs. 45.7%), in comparison to the control arm, occurred among Vectibix treated patients, while serious TEAEs (20.3% vs. 21.1%) and fatal TEAE (7.8% vs. 4.2%) did not increase. The most common types of TEAE in this study were those known common adverse reactions with Vectibix treatment (skin reactions, hypomagnesemia, etc.). No new safety signal was identified. In contrast, the safety profile of the wild-type RAS set was highly comparable to that of the overall wild-type KRAS set.

Taken together, in view of the significant and meaningful survival benefit, and the manageable safety profile, the risk benefit assessment for Vectibix in patients with chemorefractory wild-type RAS mCRC is considered favourable. The current indicated population of wild-type KRAS should be refined to wild-type RAS mCRC. Patients with mutant RAS tumours should be excluded from Vectibix treatment as they would likely gain no clinical benefit but could be exposed to the risk associated with Vectibix.