# Dynavax SD-101 Early Clinical Data: Efficacy Analysis with Small Cohort of Patients

Update 06/02/2017: Dynavax released more data for ASCO17. Now SD-101 is getting 100% ORR 7 out of 7 anti-PD-1 naive patients, including 2 Complete response (29%).  2 PR (17%) and 5 (42%) "tumor shrinkage" out of 12 anti-PD-1 progressive patients. Poster data shows 5 SD (stable disease) out of 12 anti-PD-1 progressive patients.

Update 03/06/2017: Dynavax released more data. Now SD-101 is getting 86% ORR 6 out of 7 anti-PD-1 naive patients, including 2 Complete response (29%).  1 PR and 5 stable disease out of 10 anti-PD-1 progressive patients. Dose escalation planned.

Update 11/12/2016: Dynavax just released more data. Now SD-101 is getting 80% ORR in 5 anti-PD-1 naive patients. 4 stable disease out of 8 anti-PD-1 progressive patients.

Dynavax just release early clinical data on its SD-101 and Pembrolizumab combo trial. You can find the press release here. More detailed efficacy and safety data can be found in this poster they presented at ESMO annual congress.

### Safety

Safety data was great in 16 analyzed patients, consistent with previous SD-101 trials:

No dose-limiting toxicities of the combination were observed in any dose cohort, and a maximum tolerated dose (MTD) was not identified. No immune-related adverse events were reported, and the most common treatment-emergent adverse events were grade 1-2 flu-like symptoms, including fever, chills and myalgia consistent with the engagement of TLR9 and production of interferon alpha.

### Efficacy

What's more interesting is its efficacy data. It is only available for 5 patients of the lowest dose (2mg) cohort. In four anti-PD-1-naive patients, it achieved 1 complete response and 2 partial response. In one anti-PD-1 progressor patient, it achieved stable disease.

5 patients is really a small sample size. The market apparently is not impressed by this early data release. Stock price barely moved upon the news. It kept hovering near its 52-week low due to recent AdComm cancelling drama.

### Probability Analysis

I consider this small sample size efficacy data very promising. Let's do some simple probability analysis here:

According to Merck's Keytruda webpage, Keytruda has 33% (91/277) overall response rate in melanoma, including 27% partial response and 6% complete response.

If we assume SD-101 provides no additional clinical benefit, the chance of each patient gets an overall response is 33% (1/3). The chance of getting 3 ORR out of 4 naive patients is only:

$$Ρ_4^3=4*(1/3)^3*(2/3)^1=8/81=9.9\%$$

Stable disease is not usually considered in ORR. If we choose to add it in as "Disease Control Rate", the chance of getting 4 responses out of five patients is only:

$$P_5^4=5*(1/3)^4*(2/3)^1= 10/243 = 4.1\%$$

Based on these probabilities,  I conclude the chance that SD-101 provides no additional benefit is small. On the other hand, SD-101 combo most likely provided additional clinical efficacy in treating metastatic melanoma.

Of course, a bigger sample size would have more statistical power to make such conclusions. I look forward to future data release from higher dose cohorts. I would like to see two things:

1. Will higher dose cohorts confirm the promising efficacy found in 2mg cohort?
2. Will higher dose provide a dose response effect?