bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of [fam-] trastuzumab deruxtecan (T-DXd, DS-8201a) in subjects with HER2-positive, unresectable, or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Fuchs Charles S. , Shahidi Javad , Mathew Lijoy , Qin Amy , Van Cutsem Eric 
Published: February 2020

TPS460 Background: Despite attempts, no HER2-directed therapies have been approved for gastric or GEJ cancer after disease progression on trastuzumab. [Fam-] trastuzumab deruxtecan (T-DXd, DS-8201a) is a novel HER2-targeted antibody-drug conjugate composed of a humanized monoclonal antibody specifically targeting HER2, a cleavable tetrapeptide-based linker (drug-to-antibody ratio of ≈8), and a potent topoisomerase I inhibitor payload. In a phase 1 study, T-DXd (5.4 or 6.4 mg/kg) showed promising antitumor activity in a variety of tumor types, including a confirmed objective response rate (ORR) of 43% among subjects with extensively pretreated HER2-positive gastric cancer (Shitara et al. Lancet Oncol. 2019;20(6):827-836). Here we describe the phase 2 trial evaluating the efficacy and safety of T-DXd in subjects with HER2-positive gastric/GEJ cancer previously treated with trastuzumab (NCT04014075). Methods: This is a single-arm, open-label, multicenter, phase 2 study in subjects with centrally confirmed, HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization positive), unresectable or metastatic gastric/GEJ cancer that progressed on or after first-line therapy with a trastuzumab-containing regimen. HER2 status will be confirmed by a fresh biopsy before enrollment. Subjects are excluded if they received anticancer therapy after a first-line trastuzumab-containing regimen. The study began in August 2019 and will recruit ≈ 72 subjects from 25 to 30 sites in North America and Europe. T-DXd at 6.4 mg/kg will be administered intravenously once every 3 weeks until disease progression. The primary efficacy endpoint is confirmed ORR by independent central review (ICR) using RECIST v1.1 criteria. Secondary endpoints include duration of response and progression-free survival by ICR and investigator assessment, ORR by investigator assessment, and overall survival. Additional endpoints include safety, disease control rate, and pharmacokinetic analyses. Health-related quality of life will also be measured. Clinical trial information: NCT04014075.
Phase II study of the combination of abemaciclib and pembrolizumab in locally advanced unresectable or metastatic gastroesophageal adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149.
Authors: Uboha Nataliya Volodymyrivna , Eickhoff Jens C. , Chandrasekharan Chandrikha , Jalal Shadia Ibrahim , Benson Al Bowen , Deming Dustin A. , Lindemann Stephen , Hochster Howard S. 
Published: February 2020

TPS461 Background: Metastatic gastroesophageal adenocarcinoma (GEA) has poor prognosis. Overall survival (OS) remains around 12 months (mo) with current therapies. Pembrolizumab is approved for advanced GEA that has progressed on at least 2 prior lines of systemic therapy. However, the majority of patients progress on this treatment, and less than 15% of patients experience objective response (OR). This study will evaluate efficacy of pembrolizumab in combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, abemaciclib, in patients with advanced GEA. Preclinical studies have demonstrated that CDK4/6 inhibitors can increase anti-tumor immunity and can synergize with immune checkpoint inhibitors. Based on these data, we hypothesize that abemaciclib will augment response to pembrolizumab in GEA. Methods: This is a multi-institutional, single arm, open label, phase II study of abemaciclib in combination with pembrolizumab in patients with advanced GEA who have progressed or were intolerant to at least 2 prior lines of therapy. Patients previously treated with immune checkpoint inhibitors or with microsattelite unstable tumors will be excluded. Treatments will be given on a 21 day cycle until disease progression or intolerable toxicities. Pembrolizumab, 200 mg intravenously, will be given on day 1, and abemaciclib, 150 mg, will be taken orally twice a day on days 1-21. Primary endpoint is progression free survival (PFS). Secondary endpoints include PFS rate at 6 mo, disease control rate, OS and OR rate. Correlative endpoints will examine relationship between PDL1 status, genomic signature and treatment response. Saliva samples will be collected for microbiome analysis. Archival tumor tissue and blood samples will be banked for future studies. A total of 31 evaluable subjects will be enrolled to detect an anticipated increase in the median PFS from 2 months (null hypothesis) to 4 months with 80% power at the one-sided 0.05 significance level. The trial is open to enrollment. Clinical trial information: NCT03997448.
Phase II study of trifluridine/tipiracil (FTD/TPI) and oxaliplatin as induction chemotherapy (IC) in resectable esophageal and gastroesophageal junction adenocarcinoma (EGAC).
Authors: Mukherjee Sarbajit , Assi Hussein , Fountzilas Christos , Attwood Kristopher , Boland Patrick McKay , Iyer Renuka V. , Catenacci Daniel V.T. , Hatoum Hassan 
Published: February 2020

TPS464 Background: Neoadjuvant chemoradiation (CRT) followed by surgery is a standard approach for localized EGAC. Despite multimodality treatment, 5-year overall survival (OS) is less than 50%, with pathologic complete response (pCR) rates of 20%. Achievement of pCR is associated with an improved OS. We propose to use a novel combination of FTD/TPI and oxaliplatin as IC. We hypothesize that IC before CRT will increase the pCR rate in localized EGAC. Methods: This is an open-label, multicenter phase II trial. Patients (pts) with potentially resectable loco-regional EGAC are eligible. Pts. should have adequate organ function, ECOG performance status of 0 –1, age < 76 years, and endoscopic ultrasound-determined node-positive disease with any T-stage, or T3-T4a with any N stage. Pts. with T4b or M1 disease will be excluded. Pts. will receive three cycles of IC with FTD/TPI and oxaliplatin. Based on the maximum tolerated dose (MTD) observed in a phase I trial, FTD/TPI will be administered 35 mg/m² BID, days 1–5 every 14 days, with a fixed dose of oxaliplatin 85 mg/m² (day 1). Pts will then undergo concurrent CRT (standard radiation dose of 5040 cGY will be utilized) with weekly Carboplatin (AUC 2) and Paclitaxel (50 mg/m2) for 6 weeks followed by surgery. Our primary objective is to evaluate the pCR rate. The secondary objectives include evaluation of 2-year disease-free survival (DFS), 2-year OS, and assessment of toxicities of the IC. As a correlative endpoint, circulating tumor DNA level will be correlated with disease recurrence and metabolic response on PET CT. Assuming a historic pCR rate of 20% with standard CRT, 41 pts (enrollment of up to 45 pts accounting for non-evaluable pts) are needed to show a 15% increase in pCR with IC with 80% power at one-sided significance level of α = 0.1. In stage 1, n1= 22 evaluable pts will be enrolled. If there is 5 or more pCRs, an additional n2= 19 pts will be enrolled in stage 2. If 12 or more pCRs are observed in the total n = 41 evaluable pts, then the proposed treatment regimen will be considered promising for further study. We anticipate accrual over a 2-year period from 3 sites. Clinical trial information: NCT04097028.
A phase I open-label study to investigate safety and tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of MT-5111 in subjects with HER-2 positive tumors.
Authors: Van Tine Brian Andrew , Barve Minal A. , Hamilton Erika Paige , Brenner Andrew Jacob , Wainberg Zev A. , Burnett Christine , Pelham Josh , Brieschke Brigitte , Strack Thomas 
Published: February 2020

TPS465 Background: Engineered toxin bodies (ETBs) are proprietarily engineered from a Shiga-like Toxin A subunit fused to antibody-like binding domains. ETBs can force receptor internalization, self-route to the cytosol, and induce cell-kill via inactivation of ribosomes. MT-5111 is a 55 kDa de-immunized ETB targeting HER2, and may not be subject to resistance mechanisms that exist for TKI, ADC, or antibodies. It binds a HER2 epitope distinct from trastuzumab or pertuzumab, could be combined with other HER2 targeting agents, and may have improved tumor penetration. Methods: MT-5111 is evaluated as monotherapy in subj with confirmed HER2+ locally advanced or metastatic cancers. The primary objective is to determine the maximum tolerated dose in subjects (subj) with advanced HER2-positive tumors. Secondary endpoints are PK, tumor response and immunogenicity. Part 1 will escalate doses to identify MTD in up to 42 subj. Part 2 will further evaluate MT-5111 at the MTD in up to 98 subj. All subj will receive MT-5111 on Days 1, 8, and 15 of each 21-day cycle until disease progression, unacceptable toxicity, death, withdrawal of consent or another reason for withdrawal. Part 1 will include subj with any HER2+ solid cancers. Part 2 will enroll 3 expansion cohorts: HER2+ breast (BC), HER2+ gastroesophageal cancer (GEA), and other HER2+ solid cancers. HER2+ must be demonstrated on metastatic lesions in case of metastases. Tumors tested by immunohistochemistry (IHC) must have IHC status of 2+ or 3+, regardless of in-situ hybridization (ISH) results; for BC and GEA, if no IHC is available, ISH per ASCO-CAP guidelines is used. Subj with HER2+ BC should have had at least 2 lines of HER2-directed therapy; subj with HER2+ gastric cancer should have received trastuzumab or have been intolerant to trastuzumab. Subj with evaluable disease may be included in Part 1; in Part 2, all subj must have at least 1 measurable lesion per RECIST 1.1. ECOG should be 0-1, and bone marrow, hepatic, renal, cardiac function should be adequate. Further details can be found on clinicaltrials.gov (NCT04029922). Enrollment has begun in September 2019. Clinical trial information: NCT04029922.
FIGHT-302: Phase III study of first-line (1L) pemigatinib (PEM) versus gemcitabine (GEM) plus cisplatin (CIS) for cholangiocarcinoma (CCA) with FGFR2 fusions or rearrangements.
Authors: Bekaii-Saab Tanios S. , Valle Juan W. , Van Cutsem Eric , Rimassa Lorenza , Furuse Junji , Ioka Tatsuya , Melisi Davide , Macarulla Teresa , Bridgewater John A. , Wasan Harpreet Singh , Borad Mitesh J. , Lihou Christine F. , Zhen Huiling , Féliz Luis , Asatiani Ekatherine , Jiang Ping , Vogel Arndt 
Published: February 2020

TPS592 Background: For advanced CCA, standard of care 1L systemic treatment is GEM + CIS. Genetic alterations in intrahepatic CCA provide potential therapeutic targets. Fibroblast growth factor receptor (FGFR) 2 gene rearrangements driving CCA tumorigenesis were identified almost exclusively in intrahepatic CCA patients (pts) (incidence, 10–16%). In phase 2, PEM (INCB054828), a selective, potent, oral FGFR1–3 inhibitor elicited an objective response rate (ORR) of 35.5% and median progression-free survival (PFS) of 6.9 months (mo) in previously treated, locally advanced or metastatic CCA with FGFR2 rearrangements (NCT02924376). FIGHT-302, a randomized, open-label, phase 3 study will evaluate efficacy and safety of 1L PEM vs GEM + CIS in unresectable/metastatic CCA with FGFR2 fusions or rearrangements (NCT03656536). Methods: Eligible pts are adults with confirmed unresectable/metastatic CCA; no prior systemic therapy for advanced disease < 6 mo before enrollment; radiographically measurable/evaluable disease (per RECIST v1.1); ECOG PS ≤1; documented FGFR2 fusions or rearrangements. Exclusions include clinically significant corneal or retinal disorder; history of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic soft tissue calcification; untreated CNS metastases or history of uncontrolled seizures. Pts will be randomized (1:1; stratified by region and tumor burden) to PEM 13.5 mg QD on a 21-day (d) cycle or GEM (1000 mg/m2) + CIS (25 mg/m2) on D1 and D8 of 21-d cycles (max 8). Crossover to PEM allowed after confirmed progression. PEM titration to 18 mg from cycle 2 allowed for pts without hyperphosphatemia (serum phosphate > 5.5 mg/dL) and Grade ≥2 treatment-related adverse events during cycle 1. Hyperphosphatemia will be managed with diet modifications, phosphate binders, diuretics, or dose adjustments. Treatment will continue until progression or unacceptable toxicity. Primary endpoint is PFS (by independent review). Secondary endpoints are ORR, overall survival, duration of response, disease control rate, safety, and quality of life. Four pts (target N = 432) are enrolled as of Sep 25, 2019. Clinical trial information: NCT03656536.
Phase II study of fluorouracil (FU), leucovorin (LV), and nanoliposomal irinotecan (nal-IRI) in previously treated advanced biliary tract cancer (NAPOLI-2).
Authors: Weinberg Benjamin Adam , Wang Hongkun , Pedersen Katrina , Sehdev Amikar , Sung Max W. , Hwang Jimmy J. 
Published: February 2020

TPS593 Background: Biliary tract cancers (BTCs) are rare and aggressive malignancies. The current standard of care for advanced BTC is gemcitabine (GEM) plus cisplatin . Although there is no established second-line treatment, regimens such as FOLFOX, XELOX, FOLFIRI, XELIRI, GEM, and capecitabine have activity. Nal-IRI contains IRI free base encapsulated in liposome nanoparticles which shelter IRI from conversion to its active metabolite (SN-38) and increase intratumoral levels of SN-38 compared with IRI. FU/LV/nal-IRI has shown overall survival benefit and acceptable toxicity in patients (pts) with metastatic pancreatic adenocarcinoma following GEM-based therapy in the NAPOLI-1 trial. Methods: This is a single arm, open label, multicenter phase II study of pts with advanced BTC previously treated with gemcitabine plus platinum chemotherapy. Pts will receive nal-IRI 70 mg/m2 IV over 90 minutes, LV 400 mg/m2 IV over 30 minutes, and FU 2400 mg/m2 over 46 hours, every 14 days. The primary objective is to determine progression-free survival (PFS) rate at 4 months (4mo) using RECIST v. 1.1 criteria and central radiology review. Response assessments will occur using imaging every 8 weeks. All pts who receive at least 1 dose of the study treatment will be eligible for the primary analysis. We will substitute pts who screen fail or do not begin treatment. Median PFS reported for pts receiving second-line 5-FU doublet chemotherapy is 3 months with a PFS4mo of 30%. FU/LV/nal-IRI would be of interest if it could increase the PFS4mo to 50% or higher. We will use a 2-stage Simon Minimax design. Using a one-sided α of 0.05 and 80% power, 39 pts will be required to detect a difference in PFS4mo between 30% and 50%. Assuming a dropout rate of 10%, 44 pts will be enrolled across the 5 study sites. Enrollment began in Q2 2019. Clinical trial information: NCT04005339.
Phase Ib/II study of sorafenib (SOR) and pembrolizumab (PEM) in advanced hepatocellular cancer (HCC).
Authors: Gosain Rohit , Mukherjee Sarbajit , Lee Sunyoung S. , Miller Austin , Minderman Hans , Maguire Orla , Matsuzaki Junko , Casucci Danielle , Mahalingam Devalingam , Iyer Renuka V. 
Published: February 2020

TPS596 Background: SOR has been the backbone of advanced HCC therapy with poor outcome. Anti-PD-1 therapy is approved as a second-line treatment option in HCC due to its promising efficacy and safety. Our preclinical work showed that SOR is immunomodulatory and may be synergistic when combined with anti-PD-1 therapy. Guided by this data, we initiated this multicenter study of SOR and PEM in advanced HCC patients (pts). Methods: Pts who have Child-Pugh Class A, ECOG PS of 0/1, biopsy-proven measurable HCC that is unresectable or metastatic, are included. Pts must not receive either SOR or anti-PD-1 therapy before. A total of 27 pts will be enrolled from 2 sites. Pts must have the following lab values: ANC ≥ 1,500/ mc; Hgb ≥ 8.5 g/dL; Plts ≥75,000/ mcL; serum total bilirubin ≤ 2.0 mg/dL; AST/ALT ≤ 5 X ULN; serum creatinine ≤ 1.5 X ULN. Pts with active hep B must be on antiviral therapy. Pts would be on a 4-week run-in of SOR alone at 400mg BID to ensure tolerability and stable dose (minimum 200 BID) before beginning PEM 200mg IV q3 weeks. Both drugs would be administered until progression or unacceptable toxicity with response assessment q6 weeks by RECIST 1.1 criteria. Primary endpoint: response rate. Secondary endpoints: safety, overall survival, and progression-free survival. Correlative Endpoints: Pre-treatment levels of immunosuppressive cells and the functional activity of effector T cells would be compared to post-treatment blood and tumor samples. The first 6 pts who completed 4 weeks of SOR-only treatment and began the combination therapy (addition of PEM at a fixed dose of 200 mg Q3W) would comprise the safety lead-in. Pts who withdrew before initiation of combination therapy (for reasons other than DLT) would be replaced. Dose-Limiting toxicity was defined as any ≥ grade 3 clinically significant toxicity, which is deemed possibly treatment-related and occurs within the first cycle of combination therapy. Toxicity would be assessed by NCI CTCAEV4.0. Status: First patient enrollment on 12/19/2017. On 11/28/2018, our 6th patient completed the SOR lead-in phase and began combination treatment with SOR and PEM. As of Sept 12, 2019, thirteen pts have enrolled, and 9 pts have received combination treatment. Support: Merck. Clinical trial information: NCT03211416.
A phase II, randomized, controlled trial of nivolumab in combination with BMS-986253 or cabiralizumab in advanced hepatocellular carcinoma (HCC) patients.
Authors: Welling Theodore , Beri Nina , Siolas Despina , Cohen Deirdre Jill , Becker Daniel Jacob , Zhong Hua , Wu Jennifer J. , Oberstein Paul Eliezer , Karasic Thomas Benjamin 
Published: February 2020

TPS598 Background: Tyrosine kinase inhibitors can prolong survival in advanced HCC patients, but response rates have been minimal. Recently, immune checkpoint inhibition with nivolumab (nivo) demonstrated objective response rates (ORR) of 15% (escalation phase) and 20% (expansion phase) in the Checkmate 040 study. Pre-clinical and translational studies have demonstrated that IL-8 and tumor associated macrophages (TAMs) contribute to HCC progression and recurrence following treatment. Therefore, rationale exists to evaluate combinatorial approaches to target TAM function combined with checkpoint inhibitory therapy. This phase II, randomized study will evaluate the safety and efficacy of combined anti-CSF1R (Cabiralizumab) or anti-IL-8 (BMS-986253) in combination with Nivo in advanced HCC. Methods: Advanced HCC patients without prior systemic treatment and disease measurable by RECISTv1.1 with Childs A liver function are eligible. Patients will be enrolled (n=25 per arm) to Nivo 240 mg IV Q2 weeks monotherapy, Nivo 240 mg IV + BMS-986253 1200 mg IV Q2 weeks, or Nivo 240 mg IV + Cabiralizumab 4 mg/kg IV Q2 weeks. Primary endpoints include safety and ORR determined by RECISTv1.1. Secondary endpoints include time to response, duration of response, progression free survival, and overall survival. Exploratory endpoints include analysis of tumor microenvironment immune and tumor cell profiling of pre- and on-treatment tumor tissue. Clinical trial information: NCT04050462.
A phase II trial of pembrolizumab in combination with cisplatin or carboplatin and etoposide in chemotherapy naive patients with metastatic or unresectable high-grade gastroenteropanncreatic or lung neuroendocrine carcinoma.
Authors: Ramirez Robert A. , Matrana Marc Ryan , Satti Suma , Griffin Ryan Patrick , Voros Brianne A , Bren-Mattison Yvette 
Published: February 2020

TPS635 Background: Combination chemotherapy (CTx) is the mainstay of treatment for patients with advanced high-grade gastroenteropancreatic neuroendocrine carcinoma (GEPNECs) and large cell neuroendocrine carcinomas (LCNECs) of the lung. Pembrolizumab (PEM) is a humanized antibody to the programmed cell death receptor (PD-1), which blocks the interaction with its cognate ligands, PD-L1 and PD-L2. PEM blocks the protective mechanism of cancer cells and allows the immune system to destroy them. Combination Ctx and immunotherapy has shown efficacy in other malignancies including small cell lung cancer. The purpose of this study is to test the efficacy, safety, and tolerability of combination CTx with PEM in patients with high-grade GEPNEC or LCNEC of the lung who are CTx naïve. Methods: This is an open label, phase II, single institution, multi-site trial using PEM in combination with either cisplatin or carboplatin and etoposide in patients with high grade GEPNECs or LCNEC of the lung who are CTx naïve. Patients with a histologic diagnosis of a GEPNECs with a Ki-67 of 55% or higher or a LCNEC of the lung will be eligible. Patients must be metastatic or unresectable; chemotherapy naïve; have at least one measurable lesion per RECIST 1.1, have an ECOG performance score of 0-1; and have a predicted life expectancy > 3 months. Approximately 36 GEPNEC and 6 LCNEC of the lung patients will be enrolled. Patients will receive PEM 200mg IV in combination with cisplatin 80 mg/m2 or carboplatin AUC 6 on day 1 and etoposide 100mg/m2 on days 1-3 of a 21-day cycle. Tumor response will be assessed by CT scan every 6 weeks using RECIST 1.1. Those patients who have responsive or stable disease after 4-6 cycles of platinum-based CTx will move to maintenance PEM every 3 weeks for up to 2 years. The primary endpoint will be progression free survival. Results: This study is open to enrollment. Clinical trial information: NCT03901378.
Demoralization and depression in pancreatic cancer patients.
Authors: Liu Jar-Yee , Placencio-Hickok Veronica , Anderson Brian , Oberstein Paul Eliezer , Coveler Andrew L. , Denlinger Crystal S. , Gong Jun , Hendifar Andrew Eugene 
Published: February 2020

TPS778 Background: Demoralization is a maladaptive coping response to stressful situations characterized by thoughts of hopelessness, helplessness, and loss of meaning and purpose. Psychometrically, it is measured using the Demoralization-Scale II (DS-II), a validated questionnaire that yields a patient-reported quantification (scale 0-32) of demoralization. Previous studies involving patients with progressive disease have uncovered a strong positive correlation between demoralization and depression, respectively measured by the DS-II and Patient Health Questionnaire-9 (PHQ-9) surveys. Here, we aim to characterize demoralization and its relationship to depression in pancreatic cancer patients, a unique patient population in terms of its poor prognosis. We hypothesize that demoralization is highly prevalent in the pancreatic cancer patient population and strongly correlated with depression. Methods: Eligible patients with an active pancreatic cancer diagnosis, after consenting to an IRB approved protocol, will be administered the DS-II and PHQ-9 surveys to yield psychometric measurements for analysis. The primary objective of this project is to determine the association between demoralization (DS-II) and depression (PHQ-9) in pancreatic cancer patients. Secondary objectives include associations between demoralization and ethnicity, sexual orientation, suicidal ideation, education, cancer stage, and disease progression. Data will be analyzed via simple linear regression. An ANOVA will also be conducted using DS-II groups as the categorical variable and PHQ-9 scores as the continuous variable, and vice versa. This is a multi-institutional study to be conducted at Cedars-Sinai Medical Center, New York University, University of Washington, UC San Francisco, and Lewis Katz Schools of Medicine.