On November 9, 2018 Leap Therapeutics, Inc. (NASDAQ: LPTX) reported its clinical data from its ongoing Phase I/II study of DKN-01 in combination with paclitaxel in patients with advanced esophagogastric cancer at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting (SITC 2018) (Press release, Leap Therapeutics, NOV 9, 2018, View Source [SID1234531215]).

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The esophagogastric cancer clinical trial (P102) is a multipart study of DKN-01 as a monotherapy and in combination with paclitaxel or pembrolizumab. The arms evaluating DKN-01 plus paclitaxel enrolled fifty-nine patients who had received one to seven prior lines of therapy and were designed to assess the safety, pharmacokinetics and efficacy of the combination.

The combination of DKN-01 and paclitaxel generated a 46.7% overall response rate, 19.6 weeks median progression free survival, and 61.1 weeks median overall survival in fifteen evaluable patients as a second line therapy. In the benchmark RAINBOW study, paclitaxel, as a monotherapy in second line gastroesophageal junction or gastric cancer patients, generated a 16.1% overall response rate, 2.9 months of median progression free survival, and 7.4 months median overall survival.

In addition, in the subgroup of twelve evaluable patients with heavily pre-treated esophageal squamous cell carcinoma, the combination of DKN-01 and paclitaxel produced a 33.3% overall response rate, 13.7 weeks median progression free survival, and 31.0 weeks median overall survival.

"The combination of DKN-01 and paclitaxel has generated a promising signal in second-line esophagogastric cancer patients, with clinically meaningful response rate, progression-free survival and overall survival data. In addition, there were encouraging outcomes in patients with esophageal squamous cell carcinoma, who have a significant unmet medical need and no approved therapies," commented John H. Strickler, MD, Assistant Professor of Medicine, Duke University Cancer Institute. "As GI oncologists, we are looking to improve upon the standard single agent therapies, and the combination of DKN-01 and paclitaxel merits further exploration in randomized clinical trials."

Preclinical data also presented at SITC (Free SITC Whitepaper) 2018 described the mechanism of action of DKN-01 and immune mediated anti-tumor activity in nonclinical models. A murine version of DKN-01 (mDKN-01) demonstrated efficacy in a melanoma tumor model. However, mDKN-01 was unable to impede tumor growth in immunodeficient mice, indicating that a functioning immune system is required for antibody activity. Specifically, the activity of DKN-01 was shown to require NK cells but not T or B cells, representing activation of the innate immune system. In preclinical models, the innate immune system activity of DKN-01 complemented the activity of paclitaxel and anti-PD-1 antibodies.

"To improve outcomes for patients with esophagogastric cancer, we need to develop drugs with new mechanisms of actions. The effect of DKN-01 on the innate immune system provides a strong rationale for enhanced activity in combination with chemotherapy and checkpoint inhibitors," commented Victoria M. Villaflor, MD, Associate Professor of Medicine, Northwestern University. "The DKN-01 clinical data with paclitaxel and as previously presented with Keytruda reflects the clinical translation of these complementary mechanisms and should be studied further as an important new approach for treating esophagogastric cancer patients."