bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive role of mismatch repair deficiency (MMR-D) in patients receiving first-line fluoropyrimidine and platinum (F-P) doublet chemotherapy for metastatic and locally advanced unresectable gastric cancers (GC).
Authors: Chae Heejung , Ryu Min-hee , Park Young Soo , Park Yangsoon , Moon MeeSun , Kang Yoon-Koo 
Published: February 2020

444 Background: Although adjuvant chemotherapy has been known to have a detrimental effect on MMR-D patients (pts) with resectable GC, it is unclear whether palliative chemotherapy for advanced GC would also adversely affect the survival outcome of MMR-D pts. Immune-checkpoint inhibitor (ICI) monotherapy was approved as a standard treatment for ≥ 3rd line of advanced GC and also showed a remarkable efficacy in MMR-D pts regardless of line of therapy. ICI is now being investigated in combination with 1st-line cytotoxic chemotherapy. Hence, we aim to evaluate the prognostic impact of MMR on cytotoxic chemotherapy in advanced GC. Methods: We reviewed our prospective database to identify pts with initally metastatic, recurrent and locally advanced unresectable GC who received F-P doublet from 2015 to 2018. MMR was assessed by immunohistochemistry with previously-collected tumor tissue and correlated with clinical characteristics and survival outcomes. Results: Out of 892 pts identified from the database, 543 underwent MMR test [382 initally metastatic (70.3%); 127 recurrent (23.3%); 32 locally advanced unresectable (6.3%)]. Median age was 58 years (range, 24–86) with male comprising 64.0%. MMR-D was found in 4.4% (n = 24) and associated with age ≥ 65 (50% vs 29.9%; P = 0.037), antrum-origin (62.5% vs 34.1%, P = 0.004) and well/moderately-differentiated histology (41.7% vs 25.8%, P = 0.110). According to our prognostic model (Koo DH et al, 2011), MMR-D pts were less likely to be classified into poor-risk group (4.2% vs 16.8%, P = 0.102). In good-risk group, MMR-D pts had significantly shorter PFS (6.0 vs 9.0 months, P = 0.045) and OS (10.1 vs 20.9 months, P = 0.047), while pts in moderate and poor risk group showed no difference in survival depending on MMR status. Conclusions: MMR-D GC showed significantly shorter PFS and OS on F-P doublet in good-risk pts and further investigation is needed to determine underlying molecular mechanisms. With the negative impact of MMR-D on the effect of cytotoxic chemotherapy, exclusion of MMR-D pts should be considered in future trials of ICI and cytotoxic chemothrapy combination.
Comprehensive molecular profiling of IDH1/2 mutant biliary cancers (BC).
Authors: Battaglin Francesca , Xiu Joanne , Baca Yasmine , Shields Anthony Frank , Goldberg Richard M. , Seeber Andreas , Habib Diane , Soni Shivani , Puccini Alberto , Tokunaga Ryuma , Arai Hiroyuki , Wang Jingyuan , Berger Martin D. , Astsaturov Igor A. , Lockhart Albert Craig , Zhang Wu , Marshall John , Korn W. Michael , Lenz Heinz-Josef , El-Khoueiry Anthony B. 
Published: February 2020

479 Background: Isocitrate dehydrogenases (IDH) play a key role in energetic metabolism and IDH mutations (mut) promote oncogenesis via epigenetic and genetic changes. Data addressing the molecular contexture of IDH1/2 mut in BC are lacking. We aimed to characterize the molecular profile of IDH1/2 mutant (mIDH) GI cancers with a focus on BC. Methods: 27954 GI cancer samples collected between August 2000 and July 2019 were included: 2057 BC (1159 ICC, 277 extrahepatic CC, 573 gallbladder, 48 unspecified CC), 13807 colorectal, 4183 gastric/esophageal, 3060 other. Samples were analyzed using NextGen DNA sequencing, in situ hybridization, RNA sequencing and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mut. MMR/MSI status was evaluated by a combination of IHC, Fragment Analysis and NGS. Results: mIDH frequency in BC was 10.3% (211/2057), with higher prevalence of IDH1 mut (8.2%). ICC showed the highest mut prevalence: IDH1 13.5%, IDH2 4%. Mut rates in other GI cancers types were < 1%, except for HCC (1.9%, 11/582) and small bowel (1.1%, 8/736). When compared to IDH wild type (WT), mIDH BC showed lower mut rates in TP53 (13 vs 43%), KRAS (8 vs 19%), CDKN2A (1 vs 9%), and SMAD4 (0 vs 9%), whereas PBRM1 mut were higher (14 vs 5%) ( P < .001 for all comparisons). There was a trend towards higher frequency of ARID1A and BAP1 in mIDH BC. HER2 expression and amplification rates were lower in mIDH vs WT BC (0.5 vs 3%, P = .048 and 0 vs 6%, P = .002). FGFR2 fusion was detected in 7% of WT vs 2% of mIDH BC. mIDH BC showed a lower TMB (0.7 vs 3.7%, P = .048) and a trend for lower MSI rates (0.6 vs 3%, P = .06) vs WT BC. Conversely, IDH mut were associated with higher TMB and MSI ( P < .001) and higher PD-L1 expression in other GI cancers. Conclusions: This is the largest and most extensive profiling study to investigate the molecular makeup of mIDH BC and GI tumors. Our data show distinct gene alteration patterns characterizing mIDH BC, involving genes related to chromatin remodeling and DNA repair, and a differential expression of immune related markers compared to other mIDH GI tumors. These findings can contribute to the development of rational combination therapies and to improved patient selection in the future.
CheckMate 459: Health-related quality of life (HRQoL) in a randomized, multicenter phase III study of nivolumab (NIVO) versus sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC).
Authors: Edeline Julien , Yau Thomas , Park Joong-Won , Kudo Masatoshi , Han Kwang-Hyub , Mathurin Philippe , Merle Philippe , Finn Richard S. , Müller Tobias , Taylor Fiona , Greenwood Mike , Begic Damir , Tschaika Marina , Yip Christine , Pranschke Emma , Cocks Kim , Thompson Gwilym , Blum Steven I , Wisniewski Tami , Sangro Bruno 
Published: February 2020

483 Background: SOR is approved as 1L therapy for pts with aHCC, but there is still an unmet need to help improve or maintain HRQoL. This phase 3 study compared HRQoL of NIVO vs SOR as 1L therapy in pts with aHCC as an exploratory endpoint. Methods: FACT-Hep was administered cycle 1, day 1 and every other cycle. The effect of NIVO vs SOR on HRQoL using FACT-Hep was assessed via repeated measures mixed models (MMRM). Kaplan–Meier curves and Cox proportional-hazards models determined between-treatment differences in time to first and time until definitive deterioration (TTD/TUDD) based on prespecified thresholds for minimally important differences. The GP5 item from FACT-Hep was used to assess the burden associated with treatment side effects. Results: 743 pts with aHCC were randomized to NIVO (n = 371) or SOR (n = 372). Median OS was 16.4 mo for NIVO, 14.7 mo for SOR (HR 0.85 [95% CI 0.72–1.02]; P = 0.0752). ORR was 15% for NIVO, 7% for SOR (OR 2.41 [95% CI 1.48–3.92]). HRQoL scores were completed at baseline by 94.6% and 92.5% of participants, respectively, and were similar (FACT-Hep total: NIVO 140.7 [SD 21.5] and SOR 140. 6 [SD 19.1]. Questionnaire compliance rates exceeded 70% at most visits. MMRM analyses yielded clinically meaningful and statistically significant least squares means differences favoring NIVO on FACT-Hep total (10.1 [95% CI 7.3–13.0]), physical well-being (PWB; 2.0 [95% CI 1.4–2.6]), and functional well-being (FWB; 2.5 [95% CI 1.7–3.2]) scores. No sub-scales favored sorafenib. TTD was significantly delayed in NIVO for FACT-Hep total (HR 0.62 [95% CI 0.51–0.74]), PWB (HR 0.62 [95% CI 0.52–0.74]), FWB (HR 0.73 [95% CI 0.61–0.88]), and hepatobiliary cancer subscale (HR 0.57 [95% CI 0.48–0.69]). TUDD results were consistent with TTD. A greater proportion of NIVO pts did not experience increased burden of side effects (50%–67.7%) compared with SOR (26.8%–45%) based on the GP5 item. Conclusions: These patient-reported findings demonstrate that pts taking NIVO had superior HRQoL and reduced side effect burden, further supporting clinical data showing a treatment benefit for 1L NIVO in aHCC. Clinical trial information: NCT02576509.
Treatment of metastatic colorectal cancer (mCRC) according to age.
Authors: Ortega Laura , Torres Pérez-Solero Gabriela , Arregui Valles Marta , Alva Bianchi Manuel , Aparicio Salcedo Inmaculada , García González Gonzalo , Gallego Gallego Iria , Muñoz Martín Andres J. , Calvo Ferrándiz Aitana , Blanco-Codesido Montserrat , Martin Miguel , Garcia-Alfonso Pilar 
Published: February 2020

49 Background: Elderly patients with mCRC are underrepresented in clinical trials. For this reason, the optimal treatment in this population is uncertain. The aim of this study is to compare efficacy and safety outcomes in patients with mCRC treated in our institution according to age (<65 vs ≥65 years). Methods: We conducted a retrospective analysis of 482 patients with mCRC attended in the Hospital Gregorio Marañón (Spain) between January 2010 and 2018. Results: Patients characteristics table. First-line: chemotherapy (CT) 98.7% vs 97.3% respectively (p=0.324), biologic agents (BA) 81.2% vs 79.0% (p=0.585). Significantly more <65-year-old patients received FOLFOX (60.5% vs 44.4%) and more ≥65-year-old patients XELOX (9.2% vs 17.5%) or capecitabine (2.0% vs 7.5%). Second-line: CT 64.9% vs 63.5% (p=0.764), BA 60.4% vs 51.1% (p=0.055). Significantly more <65-year-old patients received FOLFIRI (67.0% vs 54.5%) and more ≥65-year-old patients irinotecan (2.0% vs 8.6%). Third and subsequent lines: Significantly more young patients received a third-line (CT: 41.6% vs 31.0%; BA: 24% vs 21.6%), fourth-line (CT: 22.1% vs 11.9%; BA:16.2% vs 6.4%) and fifth-line of treatment (CT: 11.7% vs 5.8%; BA: 4.5% vs 3.6%). More young patients underwent metastasis resection (74.0% vs 58.1%, p=0.001). There were no differences in rate of post-operative complications (p=0.840). There were no differences in overall survival (36.05m vs 28.06, p=0.142), progression-free-survival (first-line: 12.73m vs 11.78m, p=0.139; second-line: 8.78m vs 62.71m, p=0.254) or adverse event rate (73.4% vs 73.6%, p=0.967). Conclusions: Intensive treatment could be an effectiveness and safe option in selected elderly patients. [Table: see text]
Hepatic adverse events during treatment with immune checkpoint inhibitors (ICI) in cancer patients: A territory-wide patient cohort study.
Authors: Chan Stephen Lam , Yip Terry Cheuk-Fung , Wong Vincent Wai-Sun , Chan Anthony W.H. , Tong Cathy Ka Kiu , Tse Yee Kit , Yuen Becky Wing-Yan , Luk Hester Wing-Sum , Lui Grace Chung-Yan , Chan Henry L.Y. , Mok Tony S. K. , Wong Grace Lai-Hung 
Published: February 2020

508 Background: Hepatic adverse events (AEs) are commonly encountered during ICI treatment in cancer. We evaluated the incidence and impact of hepatic AEs in a territory-wide cohort of 1509 patients who received ICI for cancer treatment. Methods: This is a territory-wide retrospective observational cohort study in Hong Kong. We identified patients through the regional hospital database (CDARS), based on the drug record of ICIs from 1 Jan 2014 to 31 Oct 2018. Serial liver functions before, during and at 3-month after ICI, were retrieved. Hepatic AEs were graded according to CTCAE 4.0. Results: The mean age was 60 years and 65.4% were male with the commonest malignancies being lung cancer (37.0%), liver cancer (17.0%) and gastrointestinal (GI) cancer (8.4%). Grade 1-2 and grade 3-4 hepatic AE occurred 39.8% and 23.3% of patients, respectively, during or within 3 months after ICI. During ICI, 39.5% developed grade 1-2 and 13.0% had grade 3-4 hepatic AE. The most common manifestations of hepatic AE occurred as elevation of ALT/AST (grade 1-2: 38.7%; grade 3-4: 10.3%). The median time of duration from ICI 1st dose to hepatic ≥ Grade 3 AE was 54 days (IQR: 22-124). Patients with liver cancer were more likely to develop hepatic AE (grade 1-2: 37.4%; grade 3-4: 55.5%). In all patients and cancer subgroup, patients with grade 3-4 hepatic AE had worse OS than grade 1-2 hepatic AE (Table). Conclusions: Hepatic AE occurs in more than half of the patients receiving ICI, with over 20% being grade 3-4 AE. Regardless of tumor types, development of hepatic AE during ICI is associated with poor prognosis. [Table: see text]
Effect of postoperative apatinib treatment after resection of hepatocellular carcinoma with portal vein invasion: A phase II study.
Authors: Sun Hui-Chuan , Zhu Xiao-Dong , Zhou Jian , Gao Qiang , Shi Ying-Hong , Ding Zhen-Bing , Huang Cheng , Qiu Shuang-Jian , Ren Ning , Shi Guo-Ming , Sun Jian , Ye Qing-Hai , Huang Xiao-Wu , Yang Xin-Rong , Fan Jia 
Published: February 2020

514 Background: Adjuvant therapy for hepatocellular carcinoma (HCC) is an unmet need. Apatinib, a VEGFR2 inhibitor, showed antitumor activity and tolerable toxicity for advanced HCC in a phase 2 study. We were aiming to explore the safety and efficacy of apatinib in adjuvant settings after resection of HCC with portal vein tumor thrombosis (PVTT). Methods: This is a single-center single-arm phase 2 study. The key inclusion criteria were: (1) pathologically confirmed HCC; (2) underwent liver resection with curative intention within 4-6 wk before recruitment; (3) PVTT assessed by preoperative imaging or intraoperative findings. Eligible pts received apatinib at 500 mg/day for a maximum of 12 mo until unacceptable toxicity or tumor recurrence. The primary outcome was recurrence-free survival (RFS) defined as the interval between surgery and the diagnosis of tumor recurrence or death from any causes whichever comes first. The secondary outcome is overall survival (OS) and treatment safety. Results: From Aug 17, 2017 to Dec 18, 2018, 49 pts were screened, and 30 pts were recruited. PVTT were classified as Vp1 (n = 7), Vp2 (n = 11), and Vp3 (n = 12) according to the LCSGJ classification. As the data cutoff on Aug 22, 2019, 4 pts are still on treatment. The median follow-up was 14.3 mo (IQR 12.3-19.3). Median duration of treatment was 4.8 mo (IQR 2.0–8.8). 20 recurrence and 2 death occurred including one death without recurrence. The mRFS was 7.6 mo (95% CI, 3.7-11.5), and the 1-year RFS rate was 36.1%. The mOS was not reached, and 1-year OS rate was 93.3% (standard error, 4.6%). Treatment-related adverse events occurred in 29 pts (96.7%). Grade 3 or 4 adverse events were reported in 14 pts (46.7%) (Table). Dose modification due to adverse events was recorded in 23 pts (76.7%). Conclusions: Apatinib is tolerant in most pts after resection for HCC with PVTT. A controlled study is warranted to prove its efficacy on tumor recurrence. Clinical trial information: NCT03261791. [Table: see text]
The Prospective Dutch Colorectal Cancer (PLCRC) Cohort: Towards a unique patient-reported outcome enriched “real-world” data cohort.
Authors: Derksen Jeroen W.G. , Elferink Marloes A.G. , Vink Geraldine R. , Roodhart Jeanine M.L. , May Anne Maria , Koopman Miriam ,   On behalf of the PLCRC Working Group
Published: February 2020

52 Background: The initiation of high-quality pan-population cohort studies is a major research priority for the improvement of colorectal cancer (CRC) outcomes as advocated by regulators and the research community. In 2013, the PLCRC cohort of the Dutch Colorectal Cancer Group was initiated in which longitudinal clinical data and patient-reported outcomes (PRO) are collected, along with pathology data and biospecimens, to serve as an infrastructure for a broad body of observational and (randomized) interventional research. Here we report on the cohort’s progress and investigate whether it develops in the direction of a nation-wide cohort of “real-world” nature. Methods: Clinical and demographical data of PLCRC participants, as prospectively collected in the Netherlands Cancer Registry by qualified data managers, were compared with the total Dutch CRC population with incidence between 2013-2017 (ref. population) which was also obtained from the Netherlands Cancer Registry. Variable distributions are compared using t-tests and χ2-tests, whereas cohort characteristics are descriptive. Results: In June 2019, 5,746 patients were enrolled in 52 / 75 Dutch hospitals, and 81% consented to receive repeated PROs. Compared to patients enrolled between 2013-16 (N = 1,093, 1-17 recruiting hospitals), we found a small shift towards the Dutch ref. population (N = 74,692) for patients enrolled between 2017-19 (N = 4,653, 17-52 hospitals) in terms of age at diagnosis (mean 64.6±10.2 years in 2013-16, 65.2±10.8 in 2017-19, and 69.5±10.9 in the ref. group), sex (65% males in 2013-16, 61% in 2017-19, and 56% in the ref. population), location of primary tumor (56% rectum in 2013-16, 40% in 2017-19, and 31% in the ref. population) and TNM stage (35% stage I-II in 2013-16, 41% in 2017-19, and 48% in the population). Conclusions: Over the past years, the number of PLCRC recruiting centers and participating patients, with high consent rates for PROs, steeply increased. Further improvements in recruitment methodologies and multidisciplinary enrolment of patients will continue to enhance PLCRC’s representation of the “real-world” and its ability to supplement trial-based evidence.
Phase III study of pembrolizumab (pembro) versus best supportive care (BSC) for second-line therapy in advanced hepatocellular carcinoma (aHCC): KEYNOTE-240 Asian subgroup.
Authors: Kudo Masatoshi , Lim Ho Yeong , Cheng Ann-Lii , Chao Yee , Yau Thomas , Ogasawara Sadahisa , Kurosaki Masayuki , Morimoto Naoki , Ohkawa Kazuyoshi , Yamashita Tatsuya , Lee Kyung-Hun , Chen Erluo , Siegel Abby B. , Ryoo Baek-Yeol 
Published: February 2020

526 Background: Pembro received accelerated approval for second-line therapy in aHCC based on KEYNOTE-224 (phase 2). KEYNOTE-240 (NCT02702401) is a randomized, phase 3 study of pembro v BSC in previously treated aHCC. We report outcomes for the Asian subgroup. Methods: Pts with a radiographic/pathologic HCC diagnosis, radiographic progression with/intolerance to sorafenib, Child-Pugh A disease, and ECOG PS 0/1 were randomized 2:1 to pembro (200 mg) + BSC or PBO + BSC Q3W (≤35 cycles or until confirmed PD/unacceptable toxicity). Pts were stratified by geographic region (Asia without Japan; non-Asia with Japan), AFP, and macrovascular invasion. Response was assessed Q6W (RECIST v1.1, central review). Primary end points: OS, PFS; secondary end points: ORR, DOR, safety. Data cutoff: Jan 2, 2019. Results: 413 pts were randomized (overall cohort: n = 278 pembro, n = 135 PBO; Asian subgroup [Hong Kong, Japan, Philippines, S Korea, Taiwan, Thailand]: n = 107, n = 50). HBV+ status and BCLC stage C were higher in Asian subgroup (HBV+: 51% v 24.5% overall; stage C: 86.6% v 79.4%). Median follow-up: pembro (21.3 mo overall; 23.5 mo); PBO (21.5 mo overall; 23.0 mo). Pembro improved OS v PBO (median OS [95% CI]: 13.9 [11.6-16.0] v 10.6 [8.3-13.5] mo; HR: 0.781; 95% CI, 0.611-0.998; P = 0.0238) and PFS (HR: 0.718; 0.570-0.904; P = 0.0022) for overall cohort and Asian subgroup (median OS: 13.8 [10.1-16.9] v 8.3 [6.3-11.8] mo; HR: 0.548; 0.374-0.804; P = 0.0009; PFS: HR: 0.475; 0.324-0.696; P < 0.0001). Differences did not meet prespecified significance level for overall cohort. ORR in overall cohort was 18.3% (14.0-23.4) for pembro; 4.4% (1.6-9.4; P = 0.00007) for PBO; in Asian subgroup, 20.6% (13.4-29.5) and 2.0% (0.1-10.6; P = 0.00135). Safety was consistent with that previously reported in pembro studies. No HBV/HCV flares were identified. Conclusions: Pembro reduced risk for death by 22% in overall cohort and 45% in Asian subgroup and improved PFS v PBO. Safety was comparable to that of pembro monotherapy. Results are consistent with KEYNOTE-224 and magnitude of OS benefit was enhanced in Asian subgroup, supporting a favorable risk-benefit balance for second-line pembro in HCC. Clinical trial information: NCT02702401.
Objective response (OR) by mRECIST to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with sorafenib in the SILIUS trial.
Authors: Kudo Masatoshi , Ueshima Kazuomi , Ogawa Chikara , Chiba Yasutaka 
Published: February 2020

534 Background: In SILIUS (NCT01214343) trial, combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve OS in patients with advanced HCC compared with sorafenib alone (Kudo M, et al. Lancet Gastroenterol Hepatol 2018). In this study, we explored the relationship between OR and OS in the sorafenib group in the SILIUS trial. Methods: Association between OR and OS in patients treated with sorafenib ( n = 103) were analyzed. The median OS of responders was compared with that of non-responders by using Mantel-Byar test to exclude guarantee-time bias. Landmark analyses were performed, as sensitivity analyses, and the effect on OS was evaluated by Cox regression analysis with OR as a time-dependent covariate, with other prognostic factors. Results: OS of responders ( n = 18) was significantly better than that of non-responders ( n = 78) ( p < 0.0001), where median OS was 27.2 (95% CI, 16.0–not reached) months for responders and 8.9 (95% CI, 6.5–12.6) months for non-responders. HRs from landmark analyses at 4, 6, and 8 months were 0.45 ( p = 0.0330), 0.37 ( p = 0.0053), and 0.36 ( p = 0.0083), respectively. OR by sorafenib was an independent predictor of OS based on unstratified Cox regression analyses. Conclusions: In the SILIUS trial, OR achieved by sorafenib per mRECIST is an independent predictor for OS in patients with HCC. [Table: see text]
SHR-1210 combined with GEMOX as first-line treatment in patients with advanced biliary tract cancer.
Authors: Chen Xiaofeng , Wu Xiaofeng , Wu Hao , Shao Qianwen , Zhu Feipeng , Qian Xiaofeng , Zhao Fengjiao , Mao Weidong , Sun Jing , Wang Jian , Han Gaohua , Li Changxian , Seesaha Poshita kumari , Wang Quanren , Li Huajun , Shao Yang , Gu Yanhong , Li Xiangcheng , Shu Yongqian 
Published: February 2020

535 Background: This study aimed to evaluate the efficacy and safety of SHR-1210 (a humanized anti-programmed cell death receptor 1 antibody) plus gemcitabine and oxaliplatin (GEMOX) as first line treatment in patients (pts) with biliary tract cancer (BTC). Methods: This was a single-arm, single-center, exploratory trial, which included advanced BTC pts. Pts received SHR-1210 (3mg/kg, total dose ≤200mg, ivd, D1/2W) combined with gemcitabine (800 mg/m2, ivd, D1/2W) and oxaliplatin (85mg/m2, ivd, D2/2W). Combined chemotherapy lasted for no more than 12 cycles. Once chemotherapy intolerance occurred or at end of 12-cycle combined chemotherapy, pts with stable disease or objective response would continue to take SHR-1210 as single agent until disease progression or intolerable toxicity. The primary endpoint was the 6-month progression free survival (PFS) rate. Results: From February 2018 to April 2019, 37 eligible pts were enrolled. The median age was 64 (range 41-74) years, male/female was 70.3/29.7%, and bile duct cancer/gallbladder cancer was 59.5/40.5%. All 37 pts were included in the safety analysis. The overall AE incidence rate was 97.3%. The incidence of grade ≥3 AEs was 73.0%, which mainly included increased GGT (gammaglutamyltransferase, 18.9%), hypokalemia (18.9%), and fatigue (16.2%). Particularly, the incidence of fever is 73.0%, in which 2 pts experienced grade 3/4 fever. Among 36 evaluable pts, 19 pts got partial response (PR, 52.8%), 14 pts stable disease (SD, 38.9%), and 3 pts progressive disease (PD, 8.3%) at best. The primary endpoint 6-month PFS rate was 50.0% (95% CI 32.4-65.4), which indicated that the primary endpoint of the study was reached, and mPFS was 6.2 months (95% CI 4.2-7.1). The 12-month overall survival (OS) rate was 50.5% (95% CI 30.6-67.4), and mOS was 12.1 months (95% CI 8.0-NA). Conclusions: This study has reached the pre-defined primary endpoint with a high response rate. Predictive biomarker analysis was reported in another abstract. Further study is needed to validate the efficacy of this combination. Clinical trial information: NCT03486678.