Avid Bioservices Inc (CDMO)

[north40000]

Recall biomarker # 3, presented at AACR 2017. It emanated from Sunrise trial in NSCLC, and is titled "IFN-Gamma analysis in blood and tissue as a potential prognostic and/or predictive biomarker."

http://www.peregrineinc.com/images/stories/pdfs/aacr2017kallinteris.pdf

I recently ran across[a handout I picked up at 2017 AACR last April] a Poster #1773 of Medimmune[AZN research arm]; Higgs is lead author. That poster is titled "Baseline IFN-gamma Gene expression Signature in Tumor Biopsies Correlates with Clinical Outcomes in Durvalumab-treated Advanced NSCLC and UC Patients"

I do not have an image of the above AZN/Medimmune poster I can place here, nor all conclusions. I do read "All biomarker results reported here should be confirmed in an independent study."

Nor do I have an image or handout of the poster of Drs. NK, Kleen, et al presented at SITC in November 2017 beyond the following:

"P87 Results of epigenetic-based quantitative PCR assisted immune cell counting analysis in bavituximab SUNRISE trial subgroup
Nikoletta L. Kallinteris1, Thomas O. Kleen2 et al

Correspondence: Nikoletta L. Kallinteris
Journal for ImmunoTherapy of Cancer 2017, 5(Suppl 2):P87
Background
SUNRISE (NCT01999673), a global, double-bind, randomized Phase III
trial of docetaxel plus bavituximab (D+B) or docetaxel plus placebo
(D+P) in previously treated non-squamous non-small cell lung cancer
(NSCLC), demonstrated similar overall survival (OS) in the intent-to treat population (n = 597). In the subgroup of 93 patients who received
subsequent immune checkpoint inhibitors (ICI), median overall
survival (mOS) was not reached (95% CI, 15.2-NA) in the D+B
group (n=46) and was 12.6 months (95% CI, 10.4-17.8) for patients in
the D+P group (n=47) (HR for death, 0.46; P = 0.006). Epigenetic based
quantitative real-time PCR assisted cell counting (qPACC) of
immune cells in blood was used to potentially identify predictive
biomarkers.
Methods
DNA was isolated from peripheral blood mononuclear cells (PBMC)
from randomized patients and treated with bisulfite leading to conversion of de-methylated cytosine (epigenetically active) residues
into uracil, but left methylated ones unaffected. The de-methylation
status of DNA regions, previously identified of being specific to respective immune cell phenotypes sorted by FACS: CD3+, CD4+, CD8+, TFH, TH17, PD1, Foxp3, naïve CD8, MDSC, CD14+, NK56+, B-cells,
GNLY, and CCR6+, was quantitated by qPACC. The number of demethylated
gene copies per biomarker was quantitated and translated
into % total of cells in the sample. Each biomarker was classified
as high or low based on the median value across all patients
and correlated to OS. Hazard ratios (HR) and confidence intervals (CI)
were estimated using a Cox proportional-hazards model.
Results
Pre-treatment (pre-tx) samples were evaluable by qPACC for 62 (32 D
+B, 30 D+P) out of the 93 patients who received ICI as next line therapy
after the SUNRISE assigned treatment. High pre-tx (≥ median)
levels correlated with statistically significant OS benefit favoring D+B
for the following biomarkers: CD3+ (HR=0.37, p=0.023), CD4+
(HR=0.32, p=0.012), CD8+ (HR=0.42, p=0.036), PD-1 (HR=0.33,
p=0.017), GNLY (HR=0.25, p=0.011), FoxP3 (HR=0.34, p=0.032), naïve
CD8+ (HR=0.32, p=0.034), B-cells (HR=0.24, p=0.007), MDSC (HR=0.33,
p=0.037) NK56+ (HR=0.29, p=0.026). Low (<) pre-tx levels of THF correlated
with OS favoring D+B (HR=0.34, p=0.033). No OS difference
was observed for pre-tx high or low levels for TH17, CCR6, or CD14+.
Conclusions
High pre-tx levels (≥median) of circulating immune cells including T
cells, B-Cells, MDSCs, NK cells correlated with significant improvement
of OS in patients who received D+B then ICI compared to D+P then ICI
in the SUNRISE trial. These results support further investigation of these markers in future bavituximab clinical trials."

Neither Dr. NK nor Dr. Kleen knew whether, or how, PPHM would proceed further with the above Conclusion and summary information in hand when I talked with them near the close of the Saturday session of SITC. That question seems to have been partially resolved by Dr. Lias during the PPHM earnings call this past Monday. Left unresolved is whether AZN might wish to proceed further with its study--I envision PPHM furnishing sufficient Bavi-family mab to combine with AZN's Durvalumab in one arm of its further independent study by way of a licensing agreement.