Ann: Final Highest Dose in Phase 1 Clinical Trial of PD-VAXX, page-183

There's a few reference to other approved drugs such as pembrolizumab (Keytruda) and nivolumab (Opdivo) which is noteworthy.

The PD1-Vaxx study specifically examined patients with non-small cell lung cancer (NSCLC) for which Keytruda is FDA-approved indication for NSCLC. The 'Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors' (Patnaik et al., 2015) in 2015 similarly examined pembrolizumab as a monotherapy but for a mixture of solid tumours. It did however include 6 patients that had NSCLC which could be potentially comparable to the preliminary results for PD1-Vaxx. There are obviously differences in study design between the clinical trials and this only intended to be illustrative. The experimental dosing will be different as well. Note that most of the patients in the pembrolizumab study received at least one previous therapy (83%). It doesn't however indicate how many of the NSCLC patients were previously treated.

In terms of the safety profile, both pembrolizumab and PD1-Vaxx were not associated with any serious adverse events. I point out that the pembrolizumab study indicated that there were no "grade 3 or 4 treatment-related AEs" (pg 4288; Patnaik et al., 2015) which I'm assuming is interchangeable with the announcement that PD1-Vaxx had "no serious adverse reactions observed at mid-dose (50μg) level".

See below for the efficacy outcomes for pembrolizumab. Take a look at the NSCLC patients (n=6). From what I can see, even at the highest dosing and shorter intervals (i.e. 2 weeks vs 3 weeks) - none of the patients experienced a partial or complete response compared to the 2 out of the 6 patients on PD1-Vaxx who reported a complete response. Not to mention that we haven't even reached the final highest dose yet for PD1-Vaxx. I haven't looked at the inclusion/exclusion criteria for each study so comparisons between the two studies should be taken with pinch of salt.

There's some additional information on Phase 1 studies related to nivolumab (Opdivo) if you're interested. One of which (Antonia et al., 2016) included 98 patients on nivolumab monotherapy at 3 mg/kg. No complete responses were reported but 10 partial responses were reported. However, note the large sample size differences. Hard to compare. The second Phase 1 study (Gettinger et al., 2014) reported an objective response rate (ORR) for nivolumab as a monotherapy for NSCLC. However, note that these were chemotherapy-naive patients whereas PD1-Vaxx was administered to patients who had previous lines of treatment.

Obviously very encouraging results about the PD1-Vaxx. It will be interesting to see (1) how durable the responses from the Cohort 1 (10μg) and Cohort 2 (50μg) will be; and (2) whether we will see additional partial/complete responses in the final dose. Very promising given that 2 patients, at 43 days and 85 days, continue to be reported as complete response. Furthermore, when this expands to PD1-Vaxx + chemotherapy - it will be interesting to see whether the combination therapy enhances the efficacy outcomes.

Good luck to us all and the patients. As always, DYOR.

Phase 1 Pembrolizumab (Keytruda)

Figure 2.Efficacy outcomes by investigatorreview per RECIST v1.1. Each barrepresents one patient. The length ofthe bar represents the duration oftreatment with pembrolizumab.Patients without a symbol for bestoverall response did not have aradiologic assessment of responseper RECIST v1.1 (Patnaik et al., 2015).



Phase 1 Nivolumab (Opdivo)

Table 2: Tumour response (Antonia et al., 2016).