A phase 1 study evaluating the safety and efficacy of DKN-01, an investigational monoclonal antibody (Mab) in patients (pts) with advanced non-small cell lung cancer.

8068 Background: DKN-01 is a high affinity neutralizing humanized Mab targeting extracellular dickkopf-1 (Dkk-1). Dkk-1 inhibits the canonical Wnt/β-catenin signaling pathway and modulates other biological pathways required for cell growth/ differentiation. Prior studies have demonstrated elevated Dkk-1 expression in lung, esophageal and gastric cancer tissue. Preclinical studies have demonstrated that a reduction of free Dkk-1 led to clinical benefit in xenograft models. Methods: A two-part (A and B) phase I, dose-finding study determined safety, maximum tolerated dose and antitumour activity infusing DKN-01 to pts with advanced malignancies with emphasis on pts with non-small cell lung cancer (NSCLC). Other endpoints were progression free survival [PFS], overall response rate [ORR], and overall survival [OS]. Part A of the study tested intravenous (IV) DKN-01 at dose levels between 75 and 600 mg administered weekly or biweekly in a 28 day cycles. For Part B, DKN-01 was administered to refractory NSCLC pts at 300 mg IV on days 1 and 15 of every 28 day cycle. Results: 32 pts enrolled in Parts A and B; 24 with NSCLC. NSCLC pts: median age 64.5 yrs, 54% male, 75% ECOG PS1, 4 median prior therapies (1-7), and 63% adenocarcinoma. DKN-01 was well tolerated with no dose limiting toxicities (DLT) or related serious adverse events (SAE). All of the treatment related AEs were ≤ Grade 2. Treatment emergent adverse events (TEAE) ≥ 15% in decreasing frequency: nausea, fatigue, decreased appetite, dyspnea, vomiting and constipation. No TEAE led to study discontinuation. Responses in 22 evaluable NSCLC pts included partial response 4.2% and stable disease 42%. One NSCLC patient had confirmed complete resolution of target disease. Median PFS in 23 evaluable NSCLC pts was 2.2 months [95% CI 1.8-2.9]. NSCLC median OS was 6.6 months (95% CI 4.1-10.1). Conclusions: DKN-01 may be a promising innovative targeted treatment for NSCLC. DKN-01 monotherapy was extremely well tolerated and demonstrated clinical activity in pts with refractory NSCLC. The median PFS and safety profile suggest that further NSCLC development in combination with other agents is warranted. Clinical trial information: NCT01457417.