Xu, Yihuan

5012 Background: VEGF receptor-mediated-signaling contributes to ovarian cancer pathogenesis. Elevated VEGF expression and serum levels are associated with poor clinical outcomes. We investigated RAM, a fully human VEGFR-2 antagonist antibody, in patients (pts) with persistent or recurrent EOC/FTC/PPC. Methods: Adult women with EOC/FTC/PPC who had completed ≥1 platinum (P)-based chemotherapeutic (ct) regimen and had a P-free interval (PFI) of <12 months (m), progression on, or persistent disease after P-based therapy were eligible. Any number of prior ct regimens was allowed. ECOG PS 0-1 and adequate organ function were required. Pts received 8 mg/kg RAM IV every 2 weeks. Primary endpoints were progression-free survival at 6m (PFS-6) and confirmed objective response rate (ORR) by RECIST 1.0. Results: 60 pts were treated; 1 remains on study as of Dec 2011. Median age was 62 years (range 27-80). Median number of prior regimens was 3 (range 1– 14). 51 pts (85%) received ≥ 2 prior regimens; 25 pts (42%) received >3 prior regimens. 45 pts (75%) were P resistant or refractory, with 65% (39 pts) serous tumors. PFS-6: 34.2% (95% CI: 21.7% – 47%). Best overall response: 3 PR (5%), 34 SD (57%), 20 PD (33%) and 3 not evaluable (5%). Median duration of PR: 5.6m (3.7, 5.6, 17.5); median PFS: 3.5m (95% CI: 2.3 – 5.3). Median OS: 11.1m (95% CI: 8.3 – 17.0). No unexpected toxicities were observed. Grade (G) 3 adverse events (AEs) observed in >5% of pts were: headache (10%) and fatigue (8%). No G4 AEs were observed in >5% of pts. 5 deaths occurred on RAM or within 30 days of discontinuation; 4 due to PD, and 1 due to intestinal perforation. 1 G4 bowel perforation and one G4 colo-vaginal fistula were noted. All 3 cases of perforation/fistula occurred in the setting of progressive, large-volume disease. Correlative biomarker studies are ongoing to identify patients most likely to benefit. Conclusions: Ramucirumab was reasonably tolerated and demonstrated single-agent activity in persistent or recurrent ovarian carcinoma, with approximately one-third of patients progression free at 6 months.

TPS2656 Background: ESCC remains the predominant histological subtype of, and accounts for most deaths from, esophageal cancer. PD-1 inhibition has demonstrated antitumor activity and was generally well tolerated in patients (pts) with advanced unresectable or metastatic ESCC. Tislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Results from early phase clinical studies suggest single-agent tislelizumab was generally well tolerated and had antitumor activity in pts with solid tumors, including ESCC. Methods: This phase 3, randomized, placebo-controlled, double-blind study (NCT03783442) is designed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment of unresectable, locally advanced recurrent or metastatic ESCC. Adult pts with histologically confirmed ESCC that had metastatic disease either at first diagnosis or with a ≥6 month treatment-free interval will be eligible. Additional eligibility criteria include measurable/evaluable disease, ECOG performance score ≤1, and no prior anti-PD-(L)-1, PD-L2, or other first-line therapy or palliative radiation treatment ≤4 weeks before treatment. Approximately 480 pts will be randomized 1:1 to receive investigator-chosen chemotherapy (ICC) plus tislelizumab 200 mg IV Q3W or ICC plus placebo. Chemotherapy options include: platinum (cisplatin 60–80 mg/m2 or oxaliplatin 130 mg/m2 IV Q3W) plus 5-FU 750–800 mg/m2 IV daily for 5 days Q3W; or platinum plus capecitabine 1000 mg/m2 orally BID for 14 days Q3W; or platinum + paclitaxel 175 mg/m2 IV Q3W. Progression-free survival and overall survival are coprimary endpoints; secondary endpoints include objective response rate, duration of response, and health-related quality-of-life. Safety will be assessed by monitoring adverse events, physical examinations, vital signs, and electrocardiograms. This study is actively enrolling. Clinical trial information: NCT03783442.