bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase II study of continuous versus intermittent S-1 plus oxaliplatin in first-line treatment of patients with metastatic gastric carcinoma.
Authors: Park Sook Ryun , Park Young-Iee , Rhee Jiyoung , Nam Byung-Ho , Kong Sun-Young , Kim Sung Hyun , Choi Mihee , Choi Il Ju , Kim Chan Gyoo , Lee Jong Yeul , Cho Soo-Jeong , Kim Young Woo , Ryu Keun Won , Lee Jun Ho , Kim Noe Kyeong 
Published: March 2020

4028 Background: We conducted a randomized phase II study to compare continuous vs. intermittent S-1 + oxaliplatin (SOX) after induction of 6 cycles of SOX in patients (pts) with metastatic gastric cancer (MGC). Methods: Pts >18 yrs with chemo-naive MGC, normal organ function, ECOG PS 0-2, and measurable or evaluable lesion(s) were initially given an induction treatment of 6 cycles of SOX (S-1 40 mg/m2 bid on D1-14 + oxaliplatin 130 mg/m2 on D1 q 3 wks). Pts with CR/PR or SD were randomized to continue SOX (arm A) until progression/intolerable toxicity or discontinue until progression when SOX was re-administered (arm B). The primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), response rate, safety, quality of life, and biomarker correlative studies. Results: From July 2007 to Dec 2010, a total of 250 pts entered into the study. Median age was 53 yrs (range, 24-69); PS 0/1/2=13/219/18; M/F=162/88. Three pts did not receive treatment and 126 (50.4%) discontinued treatment before or at the completion of 6 cycles of SOX due to progression (45.6%), pt refusal (2.8%), or adverse events (2.0%). A total of 121 pts were randomized: 59 (48.8%) to arm A and 62 (51.2%) to arm B. Clinical characteristics were well balanced between arms. SOX continuation resulted in a significant reduction in the risk of progression (median PFS, 10.5 months for arm A vs. 7.2 months for arm B; HR=0.57, 95% CI 0.39-0.84, p=0.005). With a median follow-up of 34.0 months (range, 10.5-53.3 months), there was no significant difference in OS (median OS, 22.6 months for arm A vs. 22.7 months for arm B; HR, 0.79, 95% CI 0.51-1.25, p=0.31). Arm A had higher rates of grade 3/4 fatigue (28.8% vs. 8.1%, p=0.004) and neuropathy (25.4% vs. 8.1%, p=0.014) but other grade 3/4 hematologic (neutropenia, 35.6% vs. 32.3%; thrombocytopenia, 23.7% vs. 21.0%; anemia, 15.3% vs. 6.5%) or non-hematologic toxicity rates were not significantly different. Conclusions: Continuous chemotherapy with SOX after induction therapy improved PFS but not OS. Supported by NCC Grant 1010180 (S-1 and oxaliplatin was provided by JEIL Pharm. Co., Ltd. and sanofi-aventis Korea Co., Ltd., respectively).
Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: Final analysis of a randomized phase II trial (BINGO).
Authors: Malka David , Fartoux Laetitia , Rousseau Vanessa , Trarbach Tanja , Boucher Eveline , De La Fouchardiere Christelle , Faivre Sandrine J. , Viret Frédéric , Blanc Jean-Frédéric , Assenat Eric , Hammel Pascal , Louvet Christophe , von Wichert Goetz , Ducreux Michel , Rosmorduc Olivier , Pignon Jean-Pierre , Greten Tim F 
Published: March 2020

4032 Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely accepted as first-line standard of care for patients (pts) with advanced biliary cancers (ABC). EGFR overexpression has been observed in ABC, suggesting that the combination with anti-EGFR monoclonal antibodies may be appropriate. Methods: Patients with ABC, WHO performance status (PS) 0-1, and without prior palliative CTx were eligible for this international, open-label, two-stage, non-comparative, randomized phase II trial. Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1 + oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX + cetuximab (500 mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude 4-month progression-free survival (PFS) rate (H0, <40%; H1, ≥60%; planned sample size, 100 pts, increased to 150 pts by amendment to allow subgroup analyses). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity (NCI-CTC v3.0). Exploratory endpoints included early metabolic response as assessed by PET at 1 month, and tumor KRAS mutational analysis. Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age, 62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen was well tolerated and met its primary endpoint (4-month PFS ≥60%). However, median PFS and OS were similar in both arms. Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt subgroups deriving benefit from the addition of cetuximab to CTx. [Table: see text]
Multicenter phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in pancreatic neuroendocrine tumor (PNET): Results of a planned interim efficacy analysis.
Authors: Hobday Timothy J. , Qin Rui , Reidy Diane Lauren , Moore Malcolm J. , Strosberg Jonathan R. , Kaubisch Andreas , Shah Manisha H. , Kindler Hedy Lee , Lenz Heinz-Josef , Chen Helen , Erlichman Charles 
Published: March 2020

4047 Background: PNET has long had few effective therapies other than chemotherapy. Recent placebo-controlled phase III trials of the mTOR inhibitor everolimus and the VEGF/ PDGF receptor inhibitor sunitinib noted improved progression-free survival (PFS). However, objective response rates (RR) with these agents are still <10%. Preclinical studies suggest enhanced anti-tumor effects with combined mTOR and VEGF targeted therapy. Methods: We conducted a phase II trial of the mTOR inhibitor TEM (25 mg IV q week) and the VEGF-A monoclonal antibody BEV (10 mg/kg IV q 2 weeks) in patients (pts) with well or moderately differentiated PNET and progressive disease by RECIST within 7 months of study entry. Co-primary endpoints were RR and 6-month PFS. Planned enrollment is 50 patients, with interim analysis for futility after the first 25 evaluable pts. Pts had no prior mTOR or VEGF targeted agents, ECOG PS 0-1, and adequate hematologic and organ function. Continued octreotide was allowed, but not required. Prior interferon, embolization, and ≤ 2 chemotherapy regimens were allowed. Results: Confirmed PR was documented in 13 of the first 25 (52%) evaluable patients. 21 of 25 (84%) patients were progression-free at 6 months. Both endpoints exceeded the protocol-defined criteria to continue enrollment. For 36 evaluable patients, the most common grade 3-4 adverse events attributed to therapy were hypertension (14%), leukopenia (11%), lymphopenia (11%), hyperglycemia (11%), mucositis (8%), hypokalemia (8%), and fatigue (8%). Conclusions: The combination of TEM/BEV has substantial activity in a multi-center phase II trial with RR of 52%, well in excess of single targeted agents in PNET. 6-month PFS was a notable 84% in a population of patients with RECIST criteria progression within 7 months of study entry. Accrual is ongoing.
A phase I study of nab-paclitaxel (A), gemcitabine (GEM), and capecitabine (X) in patients with metastatic pancreatic adenocarcinoma (MPA).
Authors: Truong Thach-Giao , Tempero Margaret A. , Kantoff Emily , Jones Kimberly , Dito Elizabeth , Ong Anna , Ko Andrew H. 
Published: March 2020

4048 Background: GEM-based doublets, such as GEM + capecitabine (X), may be beneficial in select pts with MPA. Given preclinical evidence of synergy when a taxane is added to GEM + X, as well as recent phase I/II study results showing substantial activity with GEM + nab-paclitaxel (A) (ORR of 48%, median OS > 12 mos at MTD), we conducted a phase I study evaluating the 3-drug combination of A, GEM, and X (AGX) given biweekly in pts with MPA. Methods: Pts with previously untreated MPA and ECOG PS 0-1 were eligible. A (100-150 mg/m2) and GEM (750-1000 mg/m2 at 10 mg/m2/min) were both administered on day 4, and X (500-1000 mg/m2 bid) on days 1-7, of each 14-day cycle. A 3+3 dose escalation design was used, with expanded cohort at MTD. Primary objective was to establish MTD of this regimen; secondary objectives include safety and preliminary assessment of efficacy. DLT definitions: gr 3-4 ANC or neutropenic fever; gr 4 plts; gr 2-4 hand-foot syndrome (HFS), neuropathy or diarrhea; or other gr 3-4 non-heme toxicity. Results: Fifteen patients were enrolled across two dose levels (age range, 45-74 y). Final MTD was established at dose level 0, consisting of A 100 mg/m2, GEM 750 mg/m2, and X 750 mg/m2 bid. At dose level 1, two of 4 pts experienced DLTs (gr 3 LFT elevation, gr 3 ANC). For the entire study cohort, 10 pts (67%) experienced at least one gr 3-4 AE, including LFTs (20%), N/V (13%), and fatigue (7%). Gr 3-4 heme toxicity was uncommon. Other notable AEs (any grade): fatigue (87%), rash/HFS (67%), N/V (53%), diarrhea (40%), neuropathy (33%). Median # cycles received = 4 (range, 2-16). 73% of pts d/c’ed study treatment due to disease progression. Best response for the entire cohort (n=14 evaluable pts): 2 PR, 8 SD, 4 PD (disease control rate = 71%). Of 12 pts with elevated CA19-9 at baseline, 5 (42%) had >50% biomarker decline. Conclusions: Recognizing the limits of cross-study comparisons and small sample size, these results do not match those reported at MTD in the phase I/II trial of GEM (1000 mg/m2) + A (125 mg/m2). The modest activity seen with this AGX regimen may have resulted from suboptimal dosing, and suggests that dose intensity may be an important factor when trying to incorporate nab-paclitaxel into multidrug regimens.
A phase I/II study of the MEK inhibitor BAY 86-9766 (BAY) in combination with gemcitabine (GEM) in patients with nonresectable, locally advanced or metastatic pancreatic cancer (PC): Phase I dose-escalation results.
Authors: Van Laethem Jean-Luc , Heinemann Volker , Martens Uwe Marc , Jassem Jacek , Michl Patrick , Peeters Marc , Weekes Colin D. , Maréchal Raphael , Stieler Jens , Giurescu Marius , Rajagopalan Prabhu , Garosi Vittorio Luigi , Riess Hanno 
Published: March 2020

4050 Background: Targeting the RAS–RAF–MEK–ERK pathway may be useful in the treatment of PC, as 75–90% of PCs have KRAS mutation. BAY is an orally bioavailable, potent, allosteric MEK 1/2 inhibitor that showed single-agent activity, and synergistic activity with GEM, in ectopic, orthotopic, syngenic and patient-derived xenograft PC models. Methods: The phase I part aimed to determine the maximum tolerated dose (MTD) of BAY in combination with GEM, and the pharmacokinetics of BAY and GEM. 3+3 study design was used. After informed consent, eligible patients with advanced PC received GEM 1000 mg/m2 (30-min, once-weekly IV infusion for 7 out of 8 weeks in cycle 1 [C1], and 3 out of 4 weeks in subsequent cycles) and oral BAY 30 mg BID (dose level 1 [DL1]) or 50 mg BID (DL2). No escalation beyond DL2 was planned. MTD was the highest dose at which maximum 1 out of 6 evaluable patients displayed dose-limiting toxicities (DLT) during C1. Results: As of 6 Jan 2012, 17 patients were enrolled and treated (10 at DL1, 7 at DL2). DL1 cohort has completed; DL2 evaluation is ongoing. At DL1, DLTs occurred in 1/6 evaluable patients: a patient with extensive liver metastasis developed chemotherapy-associated steatohepatitis (CASH) and died of hepatic failure. Rare CASH cases have been reported to be associated with GEM alone, but co-involvement of BAY currently cannot be ruled out. To date, 3 patients have completed C1 at DL2 without DLTs. DL2 completion is expected in March 2012. BAY+GEM showed a manageable tolerability profile. The most frequent treatment-related grade 3–4 adverse event (AE) at any DL was neutropenia (n=6). The most frequent clinically relevant BAY-related AE was acneiform rash (n=11), which was mostly grade 1–2 (one case grade 3) and manageable. BAY+GEM showed evidence of clinical efficacy: partial responses were seen in 4/10 patients at DL1 and 1/3 patients at DL2. No pharmacokinetic interaction between BAY and GEM was seen at DL1. Conclusions: In patients with advanced PC, BAY 30 mg BID in combination with GEM had a manageable safety profile, with acneiform rash as the clinically most relevant toxicity attributable to BAY.
Inequal benefits from regionalization of cancer care: The pancreatic cancer surgery paradigm.
Authors: McDade Theodore P. , Smith Jillian K , Chau Zeling , Witkowski Elan R. , West James K. , Tseng Jennifer F. 
Published: March 2020

4059 Background: Regionalization has been proposed for high-level care, including multidisciplinary cancer treatment and complex procedures. Pancreatic resections can serve as a marker for both. Using Massachusetts Division of Health Care Finance and Policy (DHCFP) data, we investigated regionalization of surgery for pancreatic cancer (PCa), its potential effect on perioperative outcomes, and disparities in access to high-volume PCa surgery centers. Methods: Using MA DHCFP Hospital Inpatient Discharge Data, 2005-2009, 10,524 discharges for PCa were identified, of which 746 were associated with pancreatic resection. Discharges with missing or out-of-state residence were excluded (n=704). Using geodetic methods and ZIP codes, center-to-center distances were calculated between patient (pt) and treating hospital. Median ZIP income was estimated from 2009 census data. High volume hospitals (4 of 25 performing pancreatic resections in MA) were defined using Leapfrog Criteria (> 11 per year (87th percentile for MA). Chi-square and logistic regression analyses were performed using SAS software. Results: Median age was 65. Pts were predominantly White (87.2%), with median ZIP income of $54,677. Pts travelled in-state up to 112 miles (median 15.4), with the majority resected at high volume hospitals (76%). Median length of stay (LOS) was 8.0 days, with LOS>1 week associated with low volume hospitals (p=0.0002). Of 14 in-hospital deaths, 7 were at low volume hospitals (4.14% of 169 pts) compared to 7 at high volume hospitals (1.31% of 535 pts) (p=0.0214). Predictors of shorter travel distance were: Black race (OR 4.45 (95% CI 1.66-11.93)), operation at low volume hospital (OR 2.62 (95% CI 1.81-3.77), and increased age (per year) (OR 1.02 (95% CI 1.00-1.03), but not sex or median income. Conclusions: Using MA statewide discharge data, regionalization of pancreatic cancer surgery to high-volume, better-outcome centers is seen to be occurring. However, it is not uniform, and disparities exist between groups of cancer pts that do and do not travel for their care. In the current era of scrutiny on cost, quality, and access to cancer care, further study into predictors of pts receiving optimal care is warranted.
Customization of treatment for patients with esophageal adenocarcinoma (EAC) who achieve clinical complete response (cCR) after chemoradiation using initial standardized uptake value (iSUV) of 18f-fluorodeoxyglucose PET.
Authors: Suzuki Akihiro , Xiao Lianchun , Taketa Takashi , Blum Mariela A. , Welsh James , Lin Steven H. , Weston Brian , Lee Jeffrey H , Bhutani Manoop S. , Rice David C. , Mehran Reza J. , Maru Dipen M , Erasmus Jeremy J. , Hofstetter Wayne Lewis , Swisher Stephen , Ajani Jaffer A. 
Published: March 2020

4069 Background: Patients with localized esophageal adenocarcinoma (EAC) receive preoperative chemoradiation followed by surgery (trimodality [TM] therapy) or definitive chemoradiotherapy (bimodality [BM] therapy) based on comorbidities and tumor geography. However, we cannot individualize recommendations beyond these parameters. We hypothesized that iSUV could customize therapy. Methods: Data source was our prospective database of fully staged EAC patients (2002-2010). All patients had a cCR (post-chemoradiation negative biopsy and post-chemoradiation physiologic uptake on PET). iSUV cut-point was derived by recursive partitioning. Results: For 323 cCR patients, the median follow-up was 40.8 months. 206 (63.8%) patients had TM and 117 (36.2%) had BM therapy. Median OS of TM patients and BM patients were 94.8 months (95 % CI; NA-NA) and 36.5 months (95% CI; 30.5-42.4; p<0.001), respectively. Similar differences were observed in RFS (p<0.001). The median iSUV was 9.4 (range, 0-58.0). Intriguingly, TM patients with iSUV of >6 had a better OS (94.8 months; 95% CI; 39.1-150.5) and RFS (94.8 months; 95% CI; 18.2-171.4) compared to BM patients with iSUV of >6 OS (31.4 months; 95% CI; 21.0-41.9; p=<0.001) and RFS (17.2 months; 95% CI; 14.5-19.8; p<0.001). However, the prognosis of TM and BM cCR patients with iSUV <6 was similar (OS, p=0.62 and RFS, p=0.46). The pathological CR (pathCR) rate in TM patients was similar irrespective of iSUV of ≥6 (27.1%) vs. iSUV <6 (28.6%; p=0.85). Conclusions: Our unique data provide an insight into the fate of cCR EAC patients by iSUV. Patient with iSUV ≥6 dramatically benefit from surgery and TM therapy is encouraged. iSUV and pathCR do not correlate. iSUV can customize therapy of localized EAC patients.
Efficacy and safety of bevacizumab combined with capecitabine in progressive, metastatic well-differentiated digestive endocrine tumors (BETTER study).
Authors: Mitry Emmanuel , Walter Thomas , Baudin Eric , Kurtz Jean-Emmanuel , Ruszniewski Philippe , Dominguez Sophie , Bengrine-Lefevre Leila , Cadiot Guilaume , Kraemer Sandrine , Ducreux Michel 
Published: March 2020

4071 Background: Neuroendocrine digestive tumors are highly vascularized neoplasms known to express the vascular endothelial growth factor (VEGF). We assessed the activity of bevacizumab (Bv), a monoclonal antibody directed against VEGF combined with capecitabine (CAP). Methods: In this multicenter, open-label, non-randomized, two-group phase II trial, one group assessed Bv (7.5 mg/m² on d1/3 weeks) combined with CAP (1,000 mg/m2 twice daily, orally d1-14, resumed on day 22). Eligible patients (pts) had progressive, metastatic well-differentiateddigestive tract endocrine tumors (WHO 2000 classification), ECOG-PS ≤2, Ki 67 index < 15%, no prior systemic chemotherapy and acceptable organ functions. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival, response rate, safety and quality of life. Pts were treated for a minimum of 6 months and study duration was 24 months. Results: From Jun 2007 to Oct 2009, 49 pts were enrolled, 26 (53.1%) were men; median age 60.3 years (41.2-82.3); ECOG-PS was 0/1 in 46 (93.9%) pts. Primary tumor site was: small intestine 40 (81.6%) pts, caecum 3 (6.1%), rectum 4 (8.2%) and stomach 2 (4.1%). Ki-67 proliferative index was 0-2% in 17 (35.4%) pts, 3-4% in 14 (29.2%), 5-9% in 13 (27.1%), 10-14% in 4 (8.3%) Metastatic sites were liver: 46 (93.9%) pts, lymph nodes: 24 (49.0%), peritoneum 23 (46.9%). Median treatment duration was 13.8 months; median number of cycles was 19. At 24 months, median PFS was 23.4 months [95%CI: 13.2; not reached] based on 26 events. PFS rate at 18 months was 55%. Tumor control rate was 87.8% (n=43) including partial response in 9 (18.4%) pts and stable disease in 34 (69.4%) pts. Survival rate at 24 months was 85%, median overall survival was not reached, 8 patients died. CTC grade 3/4 Adverse Events (AEs) occurred in 41 (83.7%) pts, mainly digestive 14 (28.6%) pts. Main G3/4 Bv targeted AE was hypertension in 15 (30.6%) pts. Conclusions: In this chemotherapy resistant tumor, the combination of capecitabine and bevacizumab, assessed in a phase II study, shows such encouraging results that this combination may become a reference in the medical treatment of ileal NET.
Outcome of 58 trimodality-eligible esophagogastric cancer (EC) patients who achieved clinical complete response (cCR) after preoperative chemoradiation but then declined surgery.
Authors: Taketa Takashi , Correa Arlene M , Suzuki Akihiro , Blum Mariela A. , Lee Jeffrey H , Welsh James , Lin Steven H. , Maru Dipen M , Erasmus Jeremy J. , Bhutani Manoop S. , Weston Brian , Rice David C. , Swisher Stephen , Hofstetter Wayne Lewis , Ajani Jaffer A. 
Published: March 2020

4078 Background: For patients with EC who can withstand surgery, the preferred therapy is trimodality. However, after achieving a cCR (defined as post-chemoradiation negative endoscopic biopsy for cancer and post-chemoradiation physiologic FDG uptake by PET), some patients are tempted to decline surgery. Literature is sparse on the outcome of such patients. Methods: Between 2002 and 2011, we identified 621 trimodality-eligible EC patients in our prospective database. All patients had to be trimodality-elgible and must have received preoperative chemoradiation and completed preoperative staging that included a repeat endoscopic biopsy and PET-CT prior to surgery among other routine tests. Results: Of 621 trimodality-eligible patients identified, 58 patients declined surgery after completing chemoradiation. All patients had a cCR. The median age was 69 (range, 47-85). Male (84.5%) and Caucasian (91.4%) were dominant. Baseline stage was II (44.8%) or III (51.7%) and histology was adenocarcinoma (67.2%) or squamous cell carcinoma (29.3%). 40 patients remain alive at a median follow up of 50.4 months (95% CI, 38.6-62.1). 5-year OS and relapse-free survival were 56.7±9.0% and 32.9±7.7%. Of 12 patients with local recurrence during surveillance, 11 had salvage resection. Conclusions: Although, the outcome of EC patients with cCR who declined surgery appears reasonable, in the absence of a validated prediction/prognosis model, only trimodality therapy must be encouraged for trimodality-eligible patients. Supported by UT M. D. Anderson Cancer Center grants and generous donors.
Phase I trial of temsirolimus (TEM) plus sorafenib (SOR) in advanced hepatocellular carcinoma (HCC) with pharmacokinetic (PK) and biomarker correlates.
Authors: Kelley Robin Katie , Nimeiri Halla Sayed , Munster Pamela N. , Mulcahy Mary Frances , Vergo Maxwell Thomas , DeSon Amanda , Murphy Christi , Yeh Benjamin M. , Ko Andrew H. , Korn Wolfgang Michael , Hwang Jimmy , Luttgen Madelyn , Kuhn Peter , Huang Yong , Benson Al Bowen , Venook Alan Paul 
Published: March 2020

4102 Background: Mammalian target of rapamycin inhibitors added to SOR augment antitumor effect in HCC models. We developed a phase 1 trial to determine maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of TEM plus SOR in HCC patients (pts). The study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support from Pfizer, Inc., and conducted at 2 NCCN centers. Methods: Eligibility: ≥1 measurable site. No prior systemic therapy (Tx). ECOG ≤2, Child Pugh ≤7, bilirubin ≤2 mg/dL, platelets (PLT) ≥75,000/mcL. Design: 3+3 escalation. Dose-limiting toxicity (DLT) window 28 days. MTD expansion cohort of 9 pts for PK and biomarkers. Endpoints: 1°: MTD, RP2D. 2°: Safety, toxicity, PK for TEM. Exploratory: Tumor necrosis, alpha fetoprotein (AFP)-L3, des-γ-carboxyprothrombin, and circulating tumor cells (CTC) by slide-based assay. Results: 21 pts enrolled. Median age: 60 (47-77). Male/Female: 15/6. Etiology: HCV 9 (43%), HBV 4 (19%), HBV+HCV 2 (10%), ETOH 2 (10%), unknown 4 (19%). Toxicity: DL1: 1 DLT Grade (Gr) 3 PLT. All pts required reductions for adverse events (AE); de-escalated to DL-1 for intolerability. DL-1: 1 DLT Gr3 hand-foot syndrome (HFS). Most common related ≥Gr 3 AE: HypoPO4 (52%); PLT (24%); transaminitis (19%); diarrhea, fatigue, HFS (10% each). Possibly related serious AE (SAE): Gr4 tumor rupture, Gr4 urosepsis, Gr3 dental infection with Gr2 ANC, Gr2 pneumonia (1 pt, 5% each). Best response: Confirmed partial response (PR) 2/21 (10%), stable disease (SD) 11/21 (52%), progression 1/21 (5%), 7/21 (33%) not evaluable. Time on study: Range <1 to 19+ months; median 3+ months for pts who completed ≥1 cycle (16/21). 16/21 (76%) had baseline elevated AFP ≥20; 8/16 (50%) had >50% decline. CTC were detected in 5/5 of tested samples. Decreased tumor enhancement on Tx was seen. Conclusions: DL-1 is MTD and RP2D, lower than a prior trial in pts without HCC; tolerability may be impacted by cirrhosis. Encouraging durable radiographic and AFP responses occurred. [Table: see text]