One of the main characteristics of melanoma is its ability to escape immune detection through various mechanisms, such as the loss of expression of MHC 1. Therefore, the activation of immune system will have a profound effect on melanoma. Yervoy or anti-PD1, even overexpression of GM-CSF or IL-2 should work to certain extent, despite the fact that most cases are still beyond detection. A-7, on the other hand, puts a flag on the injected lesions, thus local response rate should be high. However, A-7 does not activate the global immune response (thus minimal side effect) and neither puts “flags” on the uninjected lesions. The global response should be minimal, in the low single digits. The combination of anti-PD1 with A7 might have an additive effect.
Overall, the expectation is that the overall response rate should be between 6 and 11% with median survival extended by 2 months with a p value of 0.19 (not significant).
A simple look at the P3 trial of Yervoy + DTIC versus DTIC + placebo (over 500 treatment-naive patients) shows that your view is incorrect. At 3 years the Yervoy DTIC arm had 12.2% survivors; at 4 years the DTIC arm had 9.6% survivors. Translate these number to the A-7 DTIC arm and you have 16 DTIC survivors at 3 years and 12 at 4 years. If the A-7 unblinding occurs at average trial time of 3.5 years (soon) and 270 deaths there will be 14 DTIC survivors (116 DTIC deaths) and 106 A-7 survivors (154 deaths). 106/260 = 41% survival in A-7 arm if the A-7 and Yervoy control arms match. The Yervoy P3 control survival numbers indicate the A-7 P3 trial will be a big success.
Yervoy patient population (almost exclusive stage IV with visceral disease and majority with elevated LDH levels) is completely different. The median survival for stage IV patients from diagnosis is about 6 months with elevated LDH and 21 months with normal LDH levels respectively. Now you can see the huge difference. I pooled 5 of my oncology collogues and the consensus is that the median survival for the control arm in the P3 allovectin trial is about 17 to 19 months. If that bears out, then the allovectin trial will not have enough power to determine survival.