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e16022 Background: Individuals with gastric cancer who present with peritoneal metastasis (PM) have poor prognosis. VEGF and VEGFR-2-mediated angiogenesis can increase vascular permeability, mesothelial cell permeability and promote peritoneal metastasis and ascites formation. This study assessed whether apatinib, a small-molecule VEGFR-2 tyrosine kinase inhibitor, in combination with paclitaxel would improve survival in patients with gastric cancer with PM as second-line therapy. Methods: This was a randomized, placebo-controlled, double-blind phase 2 trial. Recruitment of the trial was stopped after 44 patients due to poor accrual. Patients aged 18 years or older with gastric adenocarcinoma with PM and disease progression after first-line chemotherapy (platinum plus fluoropyrimidine) were randomly assigned in a 1:1 ratio to receive apatinib or placebo 500 mg oral once daily plus paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR) and safety profiles. Results: Between January 2017 and January 2019, 44 patients were randomly assigned to treatment (21 in Paclitaxel/apatinib group while 23 in Paclitaxel/placebo group). Median PFS was significantly longer in apatinib plus paclitaxel group than in placebo plus paclitaxel group (4.67 months [95% CI, 3.90 to 9.13 months] vs 4.07 months [95% CI, 1.93 to 5.00 months]; hazard ratio 0.46 [95% CI, 0.22 to 0.97]; P=0.037). There was no significant difference between the two groups in median OS (8.57 months vs. 9.03 months; P=0.85), ORR (19.0% vs. 4.3%; P=0.290) and DCR (76.2% vs. 52.2%, P=0.098). Apatinib group showed a higher incidence of proteinuria (38.1% vs. 4.3%; P=0.016), while no significant difference was found in the incidence of grade 3 or higher drug-related adverse events. Conclusions: Compared with placebo plus paclitaxel, the combination of apatinib with paclitaxel as second-line therapy significantly improved median PFS with an acceptable safety profile in patients with gastric cancer with peritoneal metastasis. Clinical trial information: NCT03144843. [Table: see text]

e16059 Background: ARX788 is a novel antibody drug conjugate (ADC) that consists of human epidermal growth factor receptor 2 (HER2) targeted monoclonal antibody (mAb) linked to a cytotoxic payload, AS269, a highly potent tubulin inhibitor. In a phase 1 study of ARX788 in HER2-positive advanced breast cancer (CTR20171162/ACE-Breast-01), the objective response rate (ORR) was 74 % (14/19) at 1.5 mg/kg Q3W. Here we present the safety, tolerability, and antitumor activity of ARX788 in HER2-positive advanced gastric and gastroesophageal junction (GEJ) cancer in the phase 1 (ACE-Gastric-01) study. Methods: participants with HER2+ gastric/GEJ cancer were administrated with ARX788 intravenously at dose levels of 1.3, 1.5, and 1.7 mg/kg Q3W to determine the maximum tolerated dose and recommended phase 2 dose; and to evaluate the antitumor activity. Efficacy endpoints included objective response rate (ORR) and disease control rate (DCR) per RECIST v1.1. Results: As of Jan 29, 2021, a total of 23 participants including 9 at the 1.3 mg/kg and 14 at the 1.5 mg/kg received at least one dose of ARX788. All patients were heavily treated previously. The confirmed ORR was 42.9% and 46.2% at the 1.3 and 1.5 mg/kg, respectively. As of the cut-off date, six participants were still under treatment with two of them were treated for longer than 12 months. Most AEs were grade 1 or 2 and were manageable. There were 2 drug-related grade 3 AEs and no grade 4 or 5 AEs occurred. No DLT was observed and the MTD was not reached. The dose expansion at the 1.7 mg/kg Q3W cohort is still ongoing and the mature data will be presented later. Conclusions: ARX788 was well tolerated with promising antitumor activity in patients with HER2-positive advanced gastric and GEJ adenocarcinoma. Clinical trial information: CTR20190639. [Table: see text]

e16014 Background: Programmed cell death 1 (PD-1) inhibitors have been approved as third line therapy for patients with metastatic gastric cancer (mGC). Epstein–Barr virus (EBV)-positive is a potential predictor to response of PD-1 inhibitors. The aim of this study was to assess the efficacy and safety of camrelizumab as salvage treatment in metastatic EBV positive GC patients and explored the potential biomarkers associated with response (NCT03755440). Methods: In this prospective single-arm, phase II study, stage IV EBV positive GC patients received 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR), which were based on RECIST V.1.1. Secondary endpoints were progression free survival (PFS), overall survival (OS), disease control rate (DCR), durationn of response (DoR), and toxicity. Exploratory analysis included association between response and tumor mutational burden (TMB) and cell death ligand-1 (PD-L1) expression. Results: According to Simon’s optimum two-stage design with α = 0.05 and β = 0.20. P0 = 15% (null hypothesis), the presence of at least 1 success in the 6 patients enrolled in the first stage allowed the trial to proceed to the second stage in which 13 more patients were needed to be enrolled for the minimum total of 20 patients (5% lost to follow-up calculated). Six eligible patients were enrolled at the first stage. All the patients were HER2 negative and pMMR. None of the patients had an objective response. The DCR was 66.7%. The median PFS was 2.2 months (95% CI: 1.5 months-not reached (NR)) and median OS was 6.8 months (95% CI: 1.7 months-NR). The most common treatment-related adverse event (TRAE) was reactive cutaneous capillary endothelial proliferation. No grade 3 or worse TRAEs were found. Only one patient had PD-L1 combined positive score (CPS) ≥1 but got disease progression. Three patients were TMB > 10Mb and two of them got stable disease while one got disease progression. Conclusions: EBV positive is not a good predictor for response to PD-1 inhibitors. Potential biomarkers are needed to identify EBVaGC patients who might respond to PD-1 inhibitors. Clinical trial information: NCT03755440.

e15553 Background: PD-1 antibody monotherapy has shown durable response in colorectal cancer (CRC) patients (pts) with microsatellite instability (MSI) high status, who account for only 10–15% of all CRC pts. Preclinical studies revealed that inhibition of MAPK pathway with MEK inhibitors can increase T-cell infiltration into tumors and therefore might enhance the antitumor activity of immune checkpoint inhibitor. Thus, this study was conducted to evaluate the safety and antitumor activity of SHR7390, a MEK1/2 inhibitor, plus camrelizumab (anti-PD-1) in pts with CRC. Methods: In this single-arm, open-label, phase I study, pts with treatment-refractory advanced or metastatic CRC were enrolled to receive SHR7390 in an accelerated titration scheme at doses of 0.125, 0.25, and 0.5 mg orally qd, plus camrelizumab at a fixed dose of 200 mg IV q2w. Eligible pts were given a single dose of SHR7390, observed for 7–10 days, and then treated continuously with SHR7390 and camrelizumab in 28-day treatment cycles until disease progression, intolerable toxicities, or withdrawal of consent. A recommended dose for expansion was determined based on the safety and tolerability of the dose escalation stage. The primary endpoints were dose limiting toxicity (DLT) and maximum tolerated dose (MTD). This study is registered with ClinicalTrials.gov, number NCT03182673. Results: At data cutoff on May 30, 2020, 22 pts were enrolled. The median follow-up duration was 6 months. Seven pts had received ≥3 lines of prior treatment. MSI status were available in 21 pts (MSS/MSI-L, n = 18; MSI-H, n = 3). There were two pts each in the SHR7390 0.125 and 0.25 mg cohorts, and 0.5 mg cohort was expanded to 18 pts. One DLT (grade 3 rash) was reported in a pt in the 0.5 mg cohort and the MTD was not reached. Grade 3–4 treatment-related adverse events (TRAEs) were rash (n = 4), increased lipase, oedema peripheral, face oedema, and anemia (n = 1 each). One pt reported a grade 5 TRAE (increased intracranial pressure). Five pts (23%) achieved partial response (0.125 and 0.25 mg cohorts, n = 1 each; 0.5 mg cohort, n =3), including one out of three pts with MSS/MSI-L & BRAF mutant tumors (response lasting 13 months), one out of 15 pts with MSS/MSI-L & BRAF wild type tumors (response lasting 8 months), and all three pts with MSI-H tumors (responses lasting 31, 11, and 10 months, respectively). Three pts with MSS/MSI-L achieved stable disease, and the overall disease control rate reached 36%. Conclusions: SHR7390 plus camrelizumab showed a tolerable safety profile. Preliminary clinical activity was reported regardless of BRAF and MSI status, and future studies are warranted to further evaluate these results. Clinical trial information: NCT03182673.

121 Background: The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with MSI-H is an open question. Methods: From February 2017 to February 2020, CRC patients who received tumor specimens next-generation sequencing and detail record of clinic-pathologic information were enrolled. HER2 alteration and its relationship with MSI-H were analyzed. Results: There were totally 55 patients (7.5%) with HER2 alteration including 29 (4.0%) HER2 somatic mutations, 24 (3.3%) HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. For HER2 mutated cases, 48.3% were MSI-H, while none of HER2 amplification cases were MSI-H. MSI-H was found in 5.2% in our cohort and 36.8% MSI-H patients were HER2 mutated. MSI-H had less frequency of lung metastasis. The mPFS for first line chemotherapy was significantly higher in MSS cases than in MSI-H cases, 11.5 months vs 3.5 months, P = 0.032. MSI-H patients with HER2 mutation had significantly worse mPFS for PD-1 antibody than those without HER2 alteration, P = 0.036. Conclusions: High MSI-H rate is found in HER2 mutated cases but no MSI-H in HER2 amplification cases. MSI-H patients with HER2 mutated had worse PFS for PD-1 antibody than those without.

e15645 Background: PI3Kα is the only subtype in PI3K family of which activated mutations occur frequently in tumors. CYH33 is a potent PI3Kα–selective inhibitor with anti-tumor activity in xenograft models. An open-label, Phase I dose-escalation & expansion study of CYH33 monotherapy (NCT03544905) is underway in patients (pts) with advanced solid tumors. Methods: This study evaluates the safety, pharmacokinetics (PK), and anti-tumor activity of CYH33 administered daily orally in 28-day cycles until intolerable toxicity or disease progression (PD). Adult pts with advanced solid tumors who have progressed despite standard therapies are enrolled to this trial, and pts with or without PIK3CA mutant are eligible for dose-escalation and pts with PIK3CA mutant are eligible for dose-expansion. Results: As of the cut-off date 20 Dec 2019, 17 pts (median age 47.0 y) were enrolled in the first 6 dose levels (1mg, 5mg, 10mg, 20mg, 40mg and 60mg) of the dose-escalation cohorts, and 3 pts were enrolled in expansion cohort of 40 mg. Cohorts 1 mg to 20 mg were completed without dose-limiting toxicities (DLT), cohort 40mg was completed with 1 DLT (Grade 3 hyperglycemia) out of 6 evaluable pts, and 3 enrolled pts at 60 mg are still in the DLT evaluation. Most frequent treatment-related adverse events (TRAEs) (all grades, ≥ 20%) included hyperglycemia (17 pts, 85%), decreased appetite (5 pts, 25%), diarrhea (4 pts, 20%). Grade≥3 TRAEs were hyperglycemia (8 pts, 40%), nausea (1 pt, 5%) and decreased appetite (1 pt, 5%). Hyperglycemia was generally manageable with anti-hyperglycemic medications. The preliminary PK profile of CYH33 showed dose proportionality across the tested dose levels, half-life (t1/2) was about 20 hours with minimum accumulation, and the maximum concentration (Cmax) achieved 2-4 hours after dosing. Over all, among 15 tumor response evaluable pts, partial response (PR) was observed in 2 pts treated with 40mg (1 colorectal cancer with unknown PIK3CA mutation status, 1 breast cancer with PIK3CA mutant), and stable disease (SD) was observed in 3 pts with unknown PIK3CA mutation status. After the cut-off date, 1 more pt (ovarian cancer with PIK3CA mutation) treated with 40mg achieved PR, so that 2 out of 3 enrolled PIK3CA mutant pts treated with 40mg achieved PR. Conclusions: The first-in-human study of the PI3Kα selective inhibitor CYH33 demonstrated a manageable safety profile, linear PK, and encouraging preliminary anti-tumor activity. CYH33 single agent and in combination with other anti-tumor agents have be planned in future studies. Clinical trial information: 03544905.

3550 Background: MRG003 is a novel antibody drug conjugate (ADC) composed of a fully human anti-EGFR IgG1 monoclonal antibody conjugated to a microtubule disrupting agent monomethyl auristatin E (MMAE). MRG003 is presently being tested in an ongoing phase I study for safety, pharmacokinetics, and preliminary antitumor activity in patients (pts) with solid tumors (CTR20180310). Methods: In the phase I dose escalation study of a traditional (3+3) design, pts with relapsed or refractory cancers received single agent MRG003 once every 3 weeks (Q3W) for a maximum of 8 treatment cycles. The starting dose of MRG003 is 0.1 mg/kg, followed by 0.3, 0.6, 1.0, 1.5, 2.0, 2.5, and 3.0 mg/kg. Observations included adverse events (AEs), dose-limiting toxicity (DLT), and antitumor activity which is assessed every two cycles. Results: A total of twenty-two pts with colorectal (CRC, n = 15), nasopharyngeal (NPC, n = 3), head and neck (H&N, n = 2), esophageal (EC, n = 1), and duodenal (DC, n = 1) cancer were enrolled in the dose escalation. The median age of pts was 56.5 years. The MTD identified was 2.5 mg/kg. Commonly observed adverse events were anemia (50%), AST increase (41%), decreased appetite (41%), rash (36%), pruritus (36%), asthenia (36%), and proteinuria (32%). Majority of AEs were mild to moderate in severity. EGFR expression in patients’ tumor samples was determined retrospectively by a validated IHC method in a central laboratory. Nine out of 22 pts tested were EGFR positive. Among these 9 EGFR positive pts, one with NPC in the 2.5 mg/kg cohort had partial response, four had stable disease (one with H&N in the 1.5 mg/kg, one each with NPC and H&N in the 2.0 mg/kg, and one with EC in the 2.5 mg/kg cohorts). The disease control rate (DCR) at doses ≥1.5 mg/kg was 100% for the EGFR positive pts. Conclusions: The dose escalation study of MRG003 showed manageable safety profiles and encouraging preliminary antitumor activity in pts with EGFR-positive solid tumors. MRG003 is currently being evaluated as a single agent in phase I dose expansion cohorts to further assess safety, PK, and antitumor activity. Clinical trial information: CTR20180310 .

2593Background: APG-1387 is a bivalent small molecule Smac mimetic that antagonizes the IAPs. Preclinical studies have shown its dose- and schedule-dependent, strong antitumor activities in multipl...

4065 Background: Familial clustering is seen in 10 % of gastric cancer cases and approximately 1-3 % of gastric cancer arises in the setting of hereditary diffuse gastric cancer (HDGC). Little is known about the incidence rate and clinical-pathologic features of HDGC in Chinese patients. Methods: We retrospectively collected gastric adenocarcinoma patients who were diagnosed in Sun Yat-sen University Cancer Center between January 2002 and December 2014. All the patients had detailed record of family history and Lauren classification. All of statistical analyses were performed using the Intercooled Stata 13.0 (Stata Corporation, College Station, TX). Results: 7431 patients were enrolled for analysis. The incidence rate of HDGC was 3.97% (295/7431). There were 124 (42.03%) male and 171 (57.97%) female patients. The median age was 35 (Mean ±SD: 35.23±7.50). The most common sites were gastric body (49.47%) and fundus (35.09%) . The distribution of AJCC 7thTNM stage was 47 (16.32%) stage I, 59 (20.49%) stage II, 88 (30.55%) stage III and 94 (32.64%) stage IV. Only 92 patients received the HER2 immunohistochemistry test. 4 (4.35%) patients were HER2 IHC +++ and 8 (8.70%) patients were ++. The median survival was 80 months for the whole population and 15 months for stage IV patients. Conclusions: The incidence rate of HDGC was 3.97% in China. About one third of the patients were diagnosed at stage IV. Early detection of HDGC was warranted in China.

e15538Background: Gastric cancer is a heterogeneous disease. Whether the expression and amplification of c-Met/HER2 differ between the primary and metastatic lesion and their impacts on prognosis r...

e15533Background: Two ratio-based lymph node staging systems, the lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS), were proposed to refine the prediction of survival, but the ...

e14655 Background: In this study, we established a hypothetical tumor-lodds-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. Moreover we compared them with the 7th edition of American Joint Committee on Cancer tumor-nodes-metastasis (AJCC TNM) staging system in gastric cancer patients after D2 resection. Methods: A total of 1000 gastric carcinoma patients receiving treatment in our center were selected for the analysis. Finally, 730 patients who received D2 resection were retrospectively studied. Patients were staged using the TLM, TRM and the 7th edition AJCC TNM system. Survival analysis was performed with a Cox regression model. We used two parameters to compare the TNM, TRM and TLM staging system, the -2log likelihood and the hazard ratio. Results: The cut points of lymph node ratio (LNR) were set as 0, 0-0.3, 0.3-0.6, 0.6-1.0. And for the log odds of positive lymph nodes (LODDS), the cut points were established as≤-0.5, -0.5-0, 0-0.5, >0.5. There were significant differences in survival among patients in different LODDS classifications for each pN or LNR groups. When stratified by the LODDS classifications, the prognosis was highly homologous between those in the according pN or LNR classifications. Multivariate analysis shown that TLM staging system was better than the TRM or TNM system for the prognostic evaluation. Conclusions: The TLM systems was superior to the TRM or TNM system for prognostic assessment of gastric adenocarcinoma patients after D2 resection.

4064 Background: Two regimen sequences: folinic acid, 5-fluorouracil (FU), and irinotecan (mFOLFIRI) followed by folinic acid, FU, and oxaliplatin (mFOLFOX7; arm A), or mFOLFOX7 followed by mFOLFIR...

620 Background: There is no standard chemotherapeutic regimen for patients with advanced colorectal cancer (CRC) progressing after combination regimens including irinotecan and oxaliplatin and having good performance status. 5-FU and gemcitabine are synergistic in preclinical studies of colon cancer cells. And gemcitabine also increases intracellular release of 5-FU from capecitabine. The aim of this study is to evaluate the efficacy and tolerance of the gemcitabine/capecitabine combination as third-line treatment for patients with advanced colorectal cancer. Methods: Between May 2007 and September 2009, the data on 12 patients with metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens reviewed retrospectively. The median patient age was 54.0 years (range 37-77). The ECOG performance status was 0, 1 or 2. All patients has 2 or more previous chemotherapy. Patients received GemCap regimen (oral capecitabine 1,000 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 on days 1 and 8 every 3 weeks). Eleven patients were evaluable for the response and all patients were evaluable for toxicity. Results: No partial response was achieved and disease stabilization in 4 (36.4.3%) cases. Median progression-free survival and median overall survival were 9.1 weeks (range 3.0-18.0) and 22.3 weeks (range 10.5- 53.0). Four patients with disease stabilization had longer median progression-free survival than those with disease progression (13 weeks vs. 6.2 weeks). No toxic deaths occurred. Grade 3 toxicities were thrombocytopenia (in 2 patients), neutropenia (in 2 patients) and mucositis (in 1 patient), hand-foot syndrome (in 1 patient) and GI toxicity (in 2 patients). Conclusions: The combination of gemcitabine and capecitabine was found to be a safe palliative regimen for heavily pretreated patients with metastatic CRC. Despite no patients had radiologic response, patients with disease stabilization achieved better progression-free survival. This regimen seems to be potentially effective regimen in the treatment of CRC. No significant financial relationships to disclose.

TPS207 Background: A well-recognized standard first-line or salvage chemotherapy regimen for advanced or metastatic gastric cancer has not been established until now. Two regimen sequences—folinic acid, 5-fluorouracil (FU), and irinotecan (mFOLFIRI) followed by folinic acid, FU, and oxaliplatin (mFOLFOX7; arm A), and mFOLFOX7 followed by mFOLFIRI (arm B)—were evaluated for their antitumor activity and toxicity in Chinese patients (pts) with locally advanced or metastatic gastric cancer. Methods: Previously untreated pts between age 18 and 75 with an ECOG performance status of 0-2 and life expectancy > 4 months were eligible if they had histologically proven gastric or gastroesophageal junction adenocarcinoma with at least one site of unidimensionally measurable disease (RECIST), adequate bone marrow function (hemoglobin ≥90 g/L, absolute neutrophil count of ≥2.0×109 cells/L, and platelet count of ≥100×109 cells/L), hepatic function (alkaline phosphatases ≤3 upper limits of normal [UNL], total bilirubin ≤1...

4560 Background: We investigated the impact of expression of hypoxia inducible factor (HIF)-1α and phosphorylated Akt (p-Akt) on prognosis of gastric adenocarcinoma patients. Methods: Expressions of HIF-1α protein and p-Akt were studied by immunohistochemistry in 188 gastric adenocarcinoma patients. We investigated the impact of HIF-1α and p-Akt on survival. Furthermore we analyzed the correlation of expression of HIF-1α and p-Akt to clinicopathologic features. Results: Among 188 gastric adenocarcinoma patients, 158 (84%) and 148 (78.7%) were positive for HIF-1α and p-Akt. HIF-1α protein expression showed an impact on survival of gastric adenocarcinoma patients by both univariate and multivariate factors analysis. The median survival was significantly different between HIF-1α negative and positive patients (not reached vs 30.9 months, p=0.039, log rank test). High expressions of HIF-1α and p-Akt were significantly correlated with pTNM stage (p=0.004 for HIF-1α and p=0.031 for p-Akt), depth of invasion (p

15062 Background: The survival of advanced gastric cancer remains poor, while no chemotherapy regimen was recognized standard. Oxaliplatin and Capecitabine (Xeloda) have demonstrated promising antitumor efficacy in advanced colorectal cancer. The present study was conducted to further evaluate the efficacy and safety of XELOX (Oxaliplatin and Xeloda) regimen in gastric cancer. Methods: Patients with unresectable or metastatic gastric cancer were enrolled into this study. They all receive the XELOX regimens (Oxaliplatin 130mg/ m2 intravenously in 2 hours on day 1 followed by oral capecitabine 1000mg/ m2 twice daily for 14 days every 3 weeks).We evaluated the response every 2 cycles. Results: The median age of the total enrolled 45 patients was 55 years (range, 22–82 years), including 32 male and 13 female. They received a median of 5 cycles (range, 2–8 cycles) of XELOX. 21 of 45 patients (46.7%) achieved an objective response, 1 patient (2.2%) had completed response. 17 patients (37.8%) experienced stable disease. Median time to tumor progression (TTP) and median overall survival were not available yet due to the further follow-up needed. Most toxicity events were mild to moderate in XELOX regimen, with grade 3/4 neutropenia of 8.9 %, thrombocytopenia of 6.7%, anemia of 11.1%, hand-foot syndrome of 6.7 % and diarrhea of 6.7 %. Grade 3 neuropathy was 4.4%. The patients with advanced gastric cancer had a good tolerance to this chemotherapy. Conclusions: XELOX is a highly effective first-line treatment for unrsectable and metastatic gastric cancer. The response rates in this trial seems to be similar to those observed with FU/leucovorin/oxaliplatin combinations. XELOX is tolerable well in the treatment of advanced gastric cancer. No significant financial relationships to disclose.