On June 28, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported that CA4P in combination with a checkpoint inhibitor significantly reduced tumor size in a CT-26 colon cancer animal model (Press release, Mateon Therapeutics, JUN 28, 2017, View Source [SID1234519707]).

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Mateon evaluated its lead investigational drug CA4P, which is also currently being studied in a phase 2/3 clinical trial in platinum-resistant ovarian cancer, in a syngeneic mouse model in combination with a checkpoint inhibitor. In order to assess the effects of CA4P on more advanced and difficult-to-treat tumors, tumors in this study were allowed to grow for 13 days prior to treatment. Consequently, beginning tumor sizes were approximately three times larger than those generally evaluated in preclinical studies. Results following two weeks of treatment are as follows:



Treatment Baseline
Tumor Size Day 14
Tumor Size Day 14 Survival Survival
p-values
Vehicle 159 mm3 2005 mm3 0 / 8 Not applicable
CA4P 159 mm3 1265 mm3 2 / 8 Not significant
Anti-CTLA-4 156 mm3 1016 mm3 4 / 8 0.048
CA4P + Anti-CTLA-4 157 mm3 229 mm3 8 / 8 0.001 *
* p=0.032, Anti-CTLA-4 vs. CA4P and anti-CTLA-4

"CA4P increases the effects of checkpoint inhibitors because it rapidly causes tumor cell death, which likely increases tumor antigen presentation and T-cell activation and the overall immunologic response," said William D. Schwieterman, M.D., President and Chief Executive Officer. "These new results reinforce similar results observed in other studies and, importantly, the animals in the combination CA4P and anti-CTLA-4 antibody treatment group are continuing to show declines in tumor volume beyond Day 14. We look forward to additional data from this study and other on-going preclinical work over the next several months."

Mean Tumor Volume in CT-26 Colorectal Mouse Model
Mean Tumor Volume in CT-26 Colorectal Mouse Model


An infographic accompanying this announcement is available at View Source
This is the second study and tumor type to demonstrate robust complementary effects when Mateon’s CA4P is provided in combination with a checkpoint inhibitor; results obtained approximately four months ago in a smaller tumor EMT-6 mammary model also showed strong synergy when anti-CTLA-4 antibodies were combined with CA4P.