bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase Ib/II, multicenter, open-label study of DSP-7888 dosing emulsion in combination with immune checkpoint inhibitors (CPI) nivolumab or pembrolizumab in adult patients (pts) with advanced solid tumors, including platinum-resistant ovarian cancer (PROC).
Authors: Origuchi Makoto , Korth Chris , Li Zhonggai , Braendle Edgar E. 
Published: May 2020

TPS6099 Background: DSP-7888 is a therapeutic cancer vaccine composed of two synthetic peptides derived from Wilms’ tumor 1 (WT1) to promote both cytotoxic and helper T-lymphocyte-mediated immune responses against WT1-expressing tumors. WT1 is overexpressed in various solid tumors, including ovarian cancer. Combining cancer vaccines like DSP-7888 with a CPI may reduce resistance to immunomodulators and improve clinical benefit. A phase Ib/II study is being conducted to evaluate DSP-7888 in combination with a CPI in pts with advanced solid tumors, including PROC (NCT03311334). Methods: This phase Ib/II, open-label, multicenter, two-part dose-search/dose-expansion study investigates DSP-7888 + nivolumab or pembrolizumab in pts with advanced solid tumors (phase Ib), including PROC (phase II). The phase Ib primary objectives are safety, tolerability, and identification of the recommended phase II dose (RP2D). The phase II primary objective is evaluation of objective response rate (ORR); secondary objectives are clinical activity, safety, and tolerability. Pts aged ≥18 years with unresectable, metastatic cancer approved for treatment with nivolumab (phase Ib, Arm 1, n=6–12, 7 enrolled) or pembrolizumab (phase Ib, Arm 2, n=6–12, 6 enrolled), or with PROC (phase II) are eligible. Phase II will enroll ~40 pts into two groups based on programmed death-ligand 1 status (combined positive score of ≥10 [Group 1] or <10 [Group 2]). Clinical activity will be assessed continuously using Bayesian analysis and actual enrollment may increase by ~20 pts/group based on this analysis. Pts in phase II will receive DSP-7888 intradermally (RP2D from phase Ib) once a week (wk) for 6 wks in the induction phase then every 3 wks in the maintenance phase. Beginning Day 1, pembrolizumab will be administered intravenously every 3 wks. In phase II, objective disease will be assessed every 6 wks for 24 wks, then every 12 wks until progression. Endpoints include ORR (per RECIST v1.1) (primary), duration of response, disease control rate (DCR), progression-free survival (PFS), 6-month PFS rate (per RECIST v1.1), and overall survival, immune (i)ORR, iDCR, and iPFS (per iRECIST) (secondary). Exploratory endpoints include blood and tumor tissue biomarkers. Safety and tolerability, assessed by adverse events, will be evaluated throughout the duration of the study and follow-up. This study is currently recruiting patients. Clinical trial information: NCT03311334.
The AIM-HN and SEQ-HN study: A pivotal study evaluating the efficacy of tipifarnib in patients with head and neck squamous cell carcinoma (HNSCC) with hras mutations (AIM-HN) and the impact of hras mutations on response to first line systemic therapies for HNSCC (SEQ-HN).
Authors: Haddad Robert I. , Harrington Kevin Joseph , Licitra Lisa F. , Psyrri Amanda , Saba Nabil F. , Rajicic Natasa , Balsara Binaifer , Kurman Michael R. , Scholz Catherine Rose , Gualberto Antonio , Ho Alan Loh 
Published: May 2020

TPS6593 Background: HRAS mutations define a unique molecular subset of ~ 5% of HNSCC. Evidence suggests that these tumors respond poorly to standard systemic therapy but the impact of HRAS missense mutations on clinical outcomes has not been formally characterized. Tipifarnib is a potent and selective inhibitor of farnesyltransferase, a critical enzyme for HRAS activity. Phase 2 Proof of concept for tipifarnib in HRAS mutant HNSCC was recently achieved in study KO-TIP-001 (NCT02383927, Ho et. al. ESMO 2018). Methods: The AIM-HN and SEQ-HN Study (KO-TIP-007, NCT03719690) is an ongoing international, multicenter, open-label, 2 cohort (AIM-HN and SEQ-HN), pivotal trial designed to determine the Overall Response Rate (ORR) of tipifarnib in patients (pts) with HRAS mutant HNSCC (AIM-HN). SEQ-HN will retrospectively investigate how the ORR to first line treatment compares between the accrued HRAS mutant pts to matched-case control HRAS wild type (wt) HNSCC pts. Information on subsequent lines of therapy for HRAS mutant and wt pts will also be collected. AIM-HN will enroll at least 59 pts (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) who are refractory or have relapsed from at least one prior line of systemic platinum-based therapy and have measurable disease by RECIST 1.1. AIM-HN pts must have tumors with >35% HRAS mutant variant allele frequency (VAF) or >20% VAF if serum albumin is >3.5 g/l. AIM-HN pts will receive treatment with tipifarnib at 600 mg bid on days 1-7 and 14-21 of 28-day cycles. Using Simon's Two-Stage Minimax design, if true ORR is > 30%, the study will have 80% power to detect ORR > 15% at 0.025 significance level. Both interim (after first 31 pts) and final analysis, 2-sided 95% CI on ORR, will be performed on the modified intent to treat population. The SEQ-HN observational cohort will enroll ~225 control pts who will receive standard of care treatment. A subset of SEQ-HN pts will be matched to the HRAS mutant AIM-HN pts according to defined patient characteristics and compared for responses to therapy. Clinical trial information: NCT02383927 .
Window-of-opportunity trial of nivolumab with or without the IDO inhibitor BMS-986205 in patients with resectable squamous cell carcinoma of the head and neck (SCCHN).
Authors: Luginbuhl Adam , Johnson Jennifer Maria , Harshyne Larry , Tuluc Madalina , Gargano Stacey , Leiby Benjamin , Curry Joseph M. , Cognetti David M. , Axelrod Rita Susan , Bhateja Priyanka , Old Matthew O. , Rodeck Ulrich , Argiris Athanassios 
Published: May 2020

TPS6595 Background: Indoleamine 2,3-dioxygenase (IDO1) catabolizes tryptophan to kynurenine and is highly expressed in multiple malignancies including SCCHN. Elevated IDO1 activity may contribute to an immunosuppressive tumor microenvironment and compromise therapeutic responses to immune checkpoint therapy. We designed a window-of-opportunity trial to test whether the IDO inhibitor BMS-986305 improves treatment responses and T cell function in SCCHN patients treated with nivolumab. Methods: Patients with previously untreated, resectable, pathologically confirmed SCCHN are eligible. Primaries of the oral cavity, oropharynx, larynx, hypopharynx, or nasal cavity/paranasal sinuses must be AJCC 8th edition stage II or higher (M0). Stage I oropharyngeal cancers with lymphadenopathy are also eligible. Patients are randomized 3:1 to receive either A) nivolumab 480 mg IV x 1 plus BMS-986205 100 mg PO daily starting a week prior to nivolumab and continuing for 4 more weeks (total of 5 weeks) or B) nivolumab 480 mg IV alone for 4 weeks. At the 5th week of treatment patients are assessed for response with physical exam and repeat CT scans for tumor volumes: if there is greater than 10% reduction in volume of either primary tumor or lymph node metastases, patients will be considered responders and receive another cycle of their originally assigned treatment, i.e. nivolumab 480 mg IV for a second dose +/- BMS-986205 100 mg PO daily for an additional 4 weeks followed by surgery in week 9. If tumor volume is stable or progression is noted in either the primary site or lymph nodes, patients are considered non-responders followed by definitive surgery in week 5 (i.e. after only one cycle of treatment). The primary endpoint of this study is the response rate after cycle 1 (using the criteria defined above). The projected sample size is 48 patients (36 in arm A and 12 in arm B). Secondary endpoints include safety, pathologic treatment effect and metabolic and molecular correlates of treatment in the tumor microenvironment. Clinical trial information: NCT03854032 .
The FLEX real-world data platform explores new gene expression profiles and investigator-initiated protocols in early stage breast cancer.
Authors: D'Abreo Nina , Crozier Jennifer A. , Brufsky Adam , Grady Ian , Diab Sami , Mavromatis Blanche H. , Dul Carrie L. , Layeequr Rahman Rakhshanda , Lee Laura A. , Gadi Vijayakrishna K. , Untch Sarah , Yoder Erin , Kling Heather M. , Truitt Amy , Audeh William ,   FLEX Investigators Group
Published: May 2020

TPS7088 Background: Genomic expression profiles have enabled the classification of breast cancers into molecular sub-types and provide prognostic information about the metastatic potential of the tumor, both of which have implications for the personalized treatment of breast cancer beyond clinical and pathological features. However, to precisely stratify tumors into actionable subgroups, full genome expression data should be combined with comprehensive clinical information. The FLEX Registry aims to aggregate a large, real-world dataset, which will enable discovery of novel genomic profiles, particularly for patient subsets that are underrepresented in traditional clinical trials and will contribute to improved precision in the management of breast cancer. Methods: The FLEX Registry (NCT03053193) is a multi-center, prospective, observational trial for patients with Stage I, II, and III breast cancer. Patients with stage I-III breast cancer who receive the 70-gene signature risk of recurrence test, with or without the 80-gene signature molecular sub-typing test, on a primary tumor are eligible for enrollment. The primary objective of FLEX is to create a large scale, population-based registry that links complete clinical data with full genome expression data to elucidate new prognostic and/or predictive gene associations in a real-world setting. The FLEX Registry employs a shared study infrastructure to develop and investigate hypotheses for targeted subset analyses and/or clinical trials based on full genome expression data. The adaptable protocol is designed to be amended with the inclusion of targeted sub-studies. Patients enrolled in the initial study are eligible for inclusion in sub-studies for which they meet all eligibility criteria and additional consent is not required. Data will be collected on patients from diagnosis through 10 years of follow-up and any necessary additional clinical data will be collected as specified in the appendix protocols. Target enrollment is a minimum of 10,000 patients; >4,000 patients have enrolled since April 2017 at more than 80 sites, including seven National Cancer Institute-designated comprehensive cancer centers. The FLEX collaborative platform enables participating investigators the opportunity to author their own sub-study protocols, as approved by the FLEX Steering Committee. Fifteen sub-studies have been approved for investigation within the FLEX Registry. Clinical trial information: NCT03053193 .
A phase III, randomized, multicenter, open-label study of venetoclax or pomalidomide in combination with dexamethasone in patients with t(11;14)-positive relapsed/refractory multiple myeloma.
Authors: Mateos Maria-Victoria , Moreau Philippe , Dimopoulos Meletios A. , Hong Wan-Jen , Cooper Scott , Yu Yao , Jalaluddin Muhammad , Ross Jeremy A. , Karve Sudeep , Coppola Sheryl , Maciag Paulo Cesar , Bueno Orlando , Arriola Emma Louise , Kumar Shaji 
Published: May 2020

TPS8554 Background: BCL-2 is an anti-apoptotic protein important for myeloma cell survival. Venetoclax (Ven) is a highly selective, potent, oral BCL-2 inhibitor, that has shown promise in clinical studies as monotherapy or in combination with other agents in patients with t(11;14)-positive relapsed/refractory multiple myeloma (RRMM; Kumar et al. Blood. 2017; Costa et al. ASH 2018. Abstr. #303; Harrison et al. ASH 2019. Abstr. #142; Bahlis et al. ASH 2019. Abstr. #925; Kaufman et al. ASH 2019. Abstr. #926). Notably, t(11;14)-positive MM is more dependent on BCL-2 for cell survival, which, together with these clinical data, suggests that Ven combined with dexamethasone (Dex) may provide greater clinical benefit versus standard therapies, like pomalidomide (Pom), in this biomarker-defined patient population. This ongoing Phase 3 study (CANOVA; NCT03539744) aims to evaluate the safety and efficacy of VenDex vs PomDex in t(11;14)-positive RRMM. Methods: Eligible patients (≥18 years) must have t(11;14)-positive RRMM per central lab, an ECOG performance status ≤2, received ≥2 prior lines of therapy, previously received a proteasome inhibitor, and must be refractory to lenalidomide and last line of therapy. Patients cannot have history of treatment with Ven, Pom, or other BCL-2 inhibitors. Patients will be randomized 1:1 to Ven (800 mg orally, once-daily) or Pom (4 mg orally, once-daily on days 1-21 of 28-day cycles). Patients in both groups will receive 40 mg Dex (20 mg for patients ≥75 years) once weekly. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal from study. Patients will be stratified based on age at randomization ( < 65 vs ≥65 years), prior lines of therapy (2 to 3 vs ≥4), and International Staging System stage at screening (I vs II vs III). The primary endpoint is progression-free survival (PFS) per independent review committee (IRC) assessment based on International Myeloma Working Group criteria. The final PFS analysis will be performed when approximately 147 PFS events per IRC are observed. Secondary endpoints are response rate, patient-reported outcomes, overall survival, duration of response, times to response and progression, minimal residual disease negativity rate, safety, and Ven pharmacokinetics. Approximately 244 patients will be enrolled; as of January 21, 2020, 28 patients have been randomized (from 19 sites in 12 countries) and enrollment is ongoing. Clinical trial information: NCT03539744 .
CANOPY-A: A phase III, multicenter, randomized, double-blind, placebo-controlled trial evaluating canakinumab as adjuvant therapy in patients (pts) with completely resected non-small cell lung cancer (NSCLC).
Authors: Garon Edward B. , Ardizzoni Andrea , Barlesi Fabrice , Cho Byoung Chul , De Marchi Pedro , Goto Yasushi , Kowalski Dariusz M. , Lu Shun , Paz-Ares Luis G. , Spigel David R. , Spira Alexander I. , Thomas Michael , Leung Mimi , Baum Jason , Zhu Zewen , Oliveira Portella Maria do Socorro , Yang James Chih-Hsin 
Published: May 2020

TPS9075 Background: In the CANTOS study, canakinumab (selective IL-1β inhibitor) treatment was associated with reduced incidence and mortality from NSCLC in pts with stable post-myocardial infarction with elevated high-sensitivity C-reactive protein (hs-CRP) levels. In CANOPY-A study, we investigate the therapeutic role of canakinumab in NSCLC. Methods: The CANOPY-A study (NCT03447769) is evaluating the efficacy and safety of canakinumab as adjuvant therapy in adult pts with completely resected NSCLC. Pts with AJCC/UICC v.8 stages II–IIIA and IIIB (T > 5 cm, N2), any histology, completely resected (R0) NSCLC who completed adjuvant cisplatin-based chemotherapy (≥2 cycles) and radiotherapy (if applicable) are eligible. Pts must not have had prior neoadjuvant chemotherapy or radiotherapy. Pts (~1500) are randomized 1:1 to receive canakinumab (200 mg Q3W, SC) or placebo (Q3W, SC) for 18 cycles or until disease recurrence as determined by investigator, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, start of a new antineoplastic therapy, death, or loss to follow-up. Randomization is stratified by AJCC/UICC v.8 stage (IIA vs IIB vs IIIA vs IIIB with T > 5 cm, N2 disease), tumor histology (squamous vs non-squamous), and region (western Europe and North America vs eastern Asia vs rest of the world). Primary objective: disease-free survival (DFS) per local investigator assessment. Secondary objectives: overall survival (OS), lung cancer specific survival, safety, pharmacokinetics, immunogenicity, and patient reported outcomes. Adult pts with stage IIA–IIIA, IIIB (N2 disease only) NSCLC who are candidates for complete resection surgery (and therefore prospective candidates for the main study) will be asked to participate in a biomarker sub-study to understand how resection may impact biomarkers involved in the IL-1β inflammatory pathway and mutations present in blood. In the sub-study, the levels of hs-CRP, other cytokines, and additional biomarkers in blood will be assessed at pre- and post-surgery (endpoint: summary statistics of hs-CRP and other pharmacodynamics [PD] biomarkers). For pts who will enroll in the main study, possible associations between pre- and post-surgery biomarker levels with canakinumab efficacy will be assessed (endpoint: DFS and OS by hs-CRP and other PD biomarkers). The CANOPY-A study is currently enrolling. As of Jan 13, 2020, there are 307 study locations. Clinical trial information: NCT03447769.
Checkmate 77T: A phase III trial of neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) followed by adjuvant nivo in resectable early-stage NSCLC.
Authors: Cascone Tina , Provencio Mariano , Sepesi Boris , Lu Shun , Aanur Nivedita , Li Sunney , Spicer Jonathan 
Published: May 2020

TPS9076 Background: Although surgery for early NSCLC is potentially curative, 5-year overall survival (OS) rates for patients with stage IIA–IIIB disease are historically < 50%, representing a population of high unmet need. Conventional neoadjuvant or adjuvant chemo provides only a 5% absolute improvement in OS at 5 years. A rational approach to improve survival in these patients is to eradicate micrometastatic disease and potentially induce anti-tumor immunity to minimize the risk of relapse with peri-operative regimens including NIVO, a fully human anti–programmed death receptor-1 antibody. Early phase trials indicate that NIVO-based regimens have the potential to deepen pathological responses and extend survival in this setting (Reuss JE et al. Poster presentation at ASCO 2019. Abstract 8524; Cascone T et al. Oral presentation at ASCO 2019. Abstract 8504; Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). Data from the phase 2 single-arm NADIM trial (NCT03081689) demonstrated the highly encouraging major pathological response (MPR) rate of 83% with neoadjuvant NIVO plus chemo followed by adjuvant NIVO in patients with resectable stage IIIA NSCLC (Provencio M et al. Oral presentation at WCLC 2019. Abstract OA13.05). These results require validation in a large randomized controlled study. CheckMate 77T (NCT04025879) is a phase 3, randomized, double-blind trial evaluating neoadjuvant NIVO plus chemo followed by adjuvant NIVO in resectable early stage NSCLC. Methods: Approximately 452 patients aged ≥ 18 years with resectable stage IIA–IIIB (T3N2 only) NSCLC, ECOG performance status 0–1, and available lung tumor tissue will be enrolled at 113 sites in North America, South America, Europe, Asia, and Australia. Patients with EGFR/ALK mutations, brain metastasis, prior systemic anti-cancer treatment or radiotherapy, and autoimmune disease are excluded. Patients will be randomized to receive neoadjuvant NIVO plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant NIVO, or neoadjuvant placebo plus carboplatin- or cisplatin-based doublet chemo followed by surgery and adjuvant placebo. The primary endpoint is event-free survival, assessed by blinded independent central review. Secondary endpoints include OS, pathological complete response and MPR assessed by blind independent pathological review, safety and tolerability. The start date was September 2019. The estimated primary completion date is May 2023. Clinical trial information: NCT04025879.
A phase III trial-in-progress called REPLATINUM that compares RRx-001 + a platinum doublet to a platinum doublet in third-line or beyond small cell lung cancer.
Authors: Morgensztern Daniel , Huang Chao Hui , Rolfo Christian Diego , Ruckdeschel John C. , Dragnev Konstantin H. , Aljumaily Raid , Hauke Ralph J. , Mekhail Tarek , Fidler Mary J. , Hamm John Turner , Chiappori Alberto 
Published: May 2020

TPS9083 Background: Despite several recent checkpoint inhibitor approvals extensive stage small cell lung cancer (SCLC) is associated with a poor prognosis and remains an area of high unmet need. RRx-001 is a first-in-class, minimally toxic small molecule immunotherapeutic that inhibits c-Myc, downregulates the antiphagocytic checkpoint, CD47, repolarizes tumor associated macrophages (TAM) from protumor M2 to antitumor M1 and resensitizes to previously active first line therapies. On the basis of favorable results from a Phase 2 trial called QUADRUPLE THREAT (NCT02489903) in combination with a platinum doublet in later line SCLC, a Phase 3 trial called REPLATINUM was started in 3rd line or beyond SCLC in Q4 2019. Enrollment is ongoing. Methods: This US-based, open-label, randomized, phase 3 study (NCT03777657) compares RRx-001 4mg + a platinum doublet (carboplatin or cisplatin + etoposide) versus a platinum doublet for pts with 3rd line or beyond SCLC that have previously received a checkpoint inhibitor. Approximately 120 pts from 25 centers will be randomized 1:1 to receive RRx-001 4 mg in combination with a platinum doublet vs. a platinum doublet. The platinum doublet will be administered on both arms for up to 4 cycles; on the RRx-001 arm only patients with stable disease or better are eligible to continue on RRx-001 4 mg + carboplatin AUC 2-4 maintenance therapy. If radiologic progression occurs on the control arm prior to the 4th cycle, patients are eligible to crossover to the RRx-001 treatment arm. PFS is the primary endpoint. Secondary endpoints include OS and ORR. Exploratory endpoints include c-Myc, CD-47 and PD-L1 on circulating tumor cells and SIRP-alpha expression on circulating monocytes. Clinical trial information: NCT03777657.