Phase Ii Trial Of Tak-264 In Previously Treated Patients (Pts) With Metastatic Or Recurrent Adenocarcinoma Of The Stomach Or Gastroesophageal Junction Expression Guanylyl Cyclase C (Gcc)

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LAGastric cancer is the third-leading cause of cancer-related deaths worldwide. Outcomes of current treatment regimens remain unsatisfactory, particularly in pts with advanced gastric cancer. TAK-264 is a novel drug conjugate consisting of a human monoclonal antibody that specifically targets GCC, which is expressed in approximately 70% of gastric cancers, linked to the potent microtubule disrupting agent monomethyl auristatin E. In the first-in-human Phase 1 study ([NCT01577758][1]) evaluating the safety of TAK-264, preliminary signals of clinical activity were reported in pts with gastric, gastroesophageal, and pancreatic carcinoma. The primary objective of this Phase 2 open-label, non-randomized, multicenter study ([NCT02202759][2]) was to evaluate the overall response rate (ORR; complete response + partial response) of adult pts with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction. Here we report the findings from the Interim Analysis (IA). Pts aged ?18 years with histologically-confirmed metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction, who were GCC-positive as demonstrated by immunohistochemistry with an H score ?10 and who had received ?1 prior therapy were eligible for inclusion. TAK-264 1.8 mg/kg was administered as a single 30-minute intravenous infusion on day 1 of a 21-day cycle until disease progression or unacceptable toxicity occurred. Pts were evaluated for a response every 2 cycles. At data cut-off (October 1, 2015), 37 pts had been enrolled (81% male), of which 36 (97%) pts were response-evaluable. The median age at baseline was 63 years (range, 31-81) and the median time from the initial diagnosis was 19.7 months (range, 5-76). Pts had received a median of 3 prior therapies (range, 1-7). Of the 36 pts in the response-evaluable population, the ORR was 6% (2 pts) and stable disease was observed in 15 (42%) pts. Progressive disease was experienced by 19 (53%) pts. All pts received at least one dose of TAK-264 and were included in the safety population. Common adverse events (AEs) observed in ?15% of pts included nausea (49%), fatigue (30%), decreased appetite and asthenia (each 27%), constipation and vomiting (each 22%), peripheral edema (19%), and diarrhea and anemia (each 16%). Diarrhea and neutropenia were the most prevalent Grade ?3 AEs, (each 5%). Other Grade ?3 gastrointestinal AEs included dysphagia, nausea and decreased appetite (each 1%). Results from the current IA suggest that few pts with GCC-positive metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction experienced limited clinical benefit with TAK-264 treatment. The correlation between GCC levels and clinical outcomes is being explored. Based on the IA, these data do not support continuation of the study.Citation Format: Khaldoun Almhanna, Maria Luisa Limon Miron, David Wright, Antonio Cubillo Gracian, Richard Hubner, Jean-Luc Van Laethem, Carolina Muriel Lopez, Maria Alsina, Federico Longo Munoz, Johanna Bendell, Wells Messersmith, Huyuan Yang, Adedigbo Fasanmade, Hadi Danaee, Thea Kalebic. Phase II trial of TAK-264 in previously treated patients (pts) with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expression guanylyl cyclase C (GCC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT107. [1]: /lookup/external-ref?link_type=CLINTRIALGOVu0026access_num=NCT01577758u0026atom=%2Fcanres%2F76%2F14_Supplement%2FCT107.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOVu0026access_num=NCT02202759u0026atom=%2Fcanres%2F76%2F14_Supplement%2FCT107.atom