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The primary PFS end point was not met, although predefined exploratory biomarker analyses identified subgroups of patients in whom abituzumab may have benefit. The tolerability of abituzumab combined with cetuximab and irinotecan was acceptable. Further study is warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT01008475.

Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic inflammation. Previously, Elenagen demonstrated anti-tumor efficacy and safety in rodent tumor models and spontaneous tumors in dogs. This multicenter I/IIa trial evaluated safety and clinical activity of Elenagen in patients with advanced solid tumors. Fifteen patients were treated with escalating doses of Elenagen (1- 5 mg per doses, 5 times weekly) and additional 12 patients received 1 mg dose. Ten patients with breast and ovary cancers that progressed after Elenagen were then treated with conventional chemotherapy. Adverse events (AE) were of Grade 1; no severe AE were observed. Cumulatively twelve patients (44%) with breast, ovary, lung, renal cancer and melanoma achieved stable disease for at least 8 wks, with 4 of them (15%) had tumor control for more than 24 wks, with a maximum of 32 wks. The patients with breast and ovary cancers achieved additional tumor stabilization for 12-28 wks when treated with chemotherapy following Elenagen treatment. Therefore, Elenagen demonstrated good safety profile and antitumor activity in advanced solid tumors. Especially encouraging is its ability to restore tumor sensitivity to chemotherapy.

477 Background: We assessed RAM or MER plus standard of care GEM+CIS as first-line treatment for BTC. Methods: Patients (pts) with BTC, ECOG PS 0/1, and measurable disease were randomized 2:1:2:1 to oral MER 80 mg QD, oral PL QD, IV RAM 8 mg/kg days 1 and 8 Q3W or IV PL days 1 and 8 Q3W. Pts also received up to 8 cycles IV GEM 1000 mg/m2 + CIS 25 mg/m2 days 1 and 8 Q3W. RAM, MER, or PL could continue until disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints: overall survival (OS), objective response rate (ORR), and safety. PFS and hazard ratios (HRs) were compared using stratified log-rank tests and Cox regression models, respectively. NCT02711553. Results: 309 pts were randomized to RAM (106), MER (102), or pooled PL (101). More pts in the RAM (54.7%) and MER (49.0%) groups had baseline ECOG PS 1 vs PL (38.6%). Efficacy endpoints are in Table. Fewer pts received post-discontinuation systemic therapy in the RAM group (RAM 37.5%, MER 50.0%, PL 52.0%). The most common grade ≥3 treatment-emergent adverse events were: RAM vs PL: neutropenia (49.0% vs 33.0%), thrombocytopenia (34.6% vs 17.0%), and anemia (26.9% vs 19.0%); MER vs PL: neutropenia (47.1% vs 33.0%), thrombocytopenia (18.6% vs 17.0%), and alanine aminotransferase increased (10.8% vs 5.0%). Conclusions: PFS, OS, and ORR were not improved with the addition of RAM or MER to GEM+CIS. Treatment was well tolerated, with safety profiles consistent with known profiles for RAM, MER, and GEM+CIS. Translational studies are ongoing. Clinical trial information: NCT02711553 . [Table: see text]