bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase III study of immune checkpoint inhibition with chemotherapy in treatment-naive metastatic anal cancer patients: A trial of the ECOG-ACRIN cancer research group (EA2176).
Authors: Roth Marc Thomas , Catalano Paul J. , Ciombor Kristen Keon , Benson Al Bowen , Yao Xin , Yaeger Rona , Salem Mohamed E. , Morris Van K. , Henry David H. , Whisenant Jennifer G. , O'Dwyer Peter J. , Eng Cathy 
Published: June 2021

TPS3614 Background: Anal cancer is growing in annual incidence globally and human papillomavirus (HPV) remains the predominant risk factor underlying its development. Due to its relative rarity, clinical trials in anal cancer have historically been difficult to conduct and treatment options for metastatic disease remain limited. Carboplatin/paclitaxel (CP) was compared to cisplatin/5-fluorouracil (historical standard of care) in a recent randomized phase II clinical trial (InterAACT; EA2133) in treatment-naïve metastatic anal cancer, finding that response rates were equivocal, but that overall survival (OS) was significantly longer in the CP arm (20 months vs 12.3 months, p = 0.014). Additionally, reduced grade 3/4 toxicities were seen in the CP arm. NCI9673, a single-arm phase II study, established safety and efficacy of nivolumab in previously-treated metastatic anal cancer. Progression-free survival (PFS) was 4.1 months (95% CI 3.0-7.9) and OS was 11.5 months (95% CI 7.1-not estimable). Multiple randomized trials in lung cancer have demonstrated efficacy of platinum-based chemotherapy combined with checkpoint inhibitors. Together these studies form the rationale behind combining CP and nivolumab in treatment-naïve metastatic anal cancer. Methods: EA2176 (NCT04444921) is the first NCTN phase III randomized clinical trial in treatment-naïve metastatic anal cancer. Stratification factors include HIV status and history of chemoradiation for curative intent. Patients will be randomized to carboplatin (AUC = 5, Day 1) plus paclitaxel (80mg/m2, Days 1, 8, 15) +/- nivolumab 240mg IV (Cycle 1 = Days 1, 15; Cycle ≥2 = Day 1, 480mg) q 28-days until disease progression or treatment intolerance. CP will be given for up to 6 cycles, while nivolumab will be continued as maintenance for up to 2 years. The primary endpoint is PFS. Secondary objectives include OS, response rate, and toxicity. Goal enrollment is 205 patients and the study continues accrual. This sample size will provide 80% power at a two-sided α of 0.05 to detect a 4.8-month improvement in PFS assuming 8 months in the control arm. Novel correlative studies include sequential quantitative tumor-derived cell-free HPV ctDNA levels (serotypes 16 and 18; Sysmex-Inostics SafeSEQ NGS assay). Correlative funding provided in part by the Farrah Fawcett Foundation and Sysmex Inostics, Inc. Clinical trial information: NCT04444921.
TGF-β and PD-L1 inhibition combined with definitive chemoradiotherapy in esophageal squamous cell carcinoma: A phase II clinical trial (NCT04595149).
Authors: Veen Linde , Hulshof Maarten C.C.M. , Jimenez Connie R. , Cuppen Edwin P.J.G. , Beerepoot Laurens V. , Creemers Geert-Jan , Fiets W. Edward , Jeene Paul M. , Lipman Djoeri , Haj Mohammad Nadia , Oppedijk Vera , Slingerland Marije , Vervenne Walter L. , Bijlsma Maarten F. , Van Laarhoven Hanneke W.M. 
Published: June 2021

TPS4154 Background: Esophageal cancer is the 6th leading cause of mortality worldwide, with an overall 5-year survival rate of 10%. This is in part due to more than 50% of patients presenting with irresectable or metastatic disease. With the introduction of definitive chemoradiation, 3-year survival rates of patients with irresectable tumors have risen to up to 40% (Hulshof et al., ASCO GI Oral Presentation, 2020). However, treatment still fails in the majority of patients due to locoregional recurrences or development of metastatic disease. Recently, it has been shown that addition of TGF-β inhibition to chemoradiation may improve treatment efficacy (Steins et al., Int J Cancer, 2019). Additionally, PD-L1 inhibition has emerged as a relevant therapeutic strategy in specific patient subgroups, such as squamous cell carcinoma (Kato et al., The Lancet Oncology, 2019). In this phase II study, we will investigate the feasibility of addition of bintrafusp alfa, a bifunctional fusion protein blocking TGF-β and PD-L1, to definitive chemoradiation in patients with esophageal squamous cell carcinoma. Methods: To assess feasibility, 52 patients will receive definitive chemoradiation combined with three doses of bintrafusp alfa at week 1, 4 and 7 (Table). Feasibility is defined as ≥80% of patients completing 2 cycles of bintrafusp alfa and will be tested with a one-sample test for a binomial proportion, comparing the observed percentage to the fixed reference value of unfeasibility (62%). Secondary endpoints are toxicity, progression-free survival, overall survival and quality of life. Additionally, exploratory endpoints include development of biomarkers to predict treatment response. Eligible for inclusion are patients with surgically irresectable (T1-4a N+ M0) squamous cell carcinoma of the esophagus or gastro-esophageal junction, or patients with resectable tumors refraining from radical surgery. Patients with M1 disease solely on the basis of supraclavicular metastasis are eligible. Patients with locoregional recurrences are eligible, provided that full dose of radiation can be safely delivered. Currently, 2 of planned 52 patients have been enrolled. Clinical trial information: NCT04595149. [Table: see text]
Trial in progress: A phase 1, multicenter, open-label, dose-exploration and dose-expansion study evaluating the safety, tolerability, pharmacokinetics, and efficacy of AMG650 in subjects with advanced solid tumors.
Authors: Govindan Ramaswamy , Townsend Amanda Rose , Miller Kathy D. , Mehmi Inderjit , Kuboki Yasutoshi , Dumbrava Ecaterina Elena , Hamilton Erika P. , Vuu Irene , Rasmussen Erik , Mileshkin Linda R. , Genta Sofia , Iwata Hiroji , Adams Sylvia , Fujii Hisaki , Chawla Sant P. 
Published: June 2021

TPS5600 Background: KIF18A is a mitotic kinesin motor protein that regulates chromosome positioning during cell division and is overexpressed in a subset of human cancers. TP53 mutant unstable aneuploid cancer cells with chromosomal instability (CIN) features are dependent on KIF18A motor activity to prevent lethal multipolar cell division. Preclinical data demonstrate that treatment with AMG 650; an oral, first in class, selective small molecule inhibitor of KIF18A may be safe and tolerable. We are conducting a first-in-human phase 1 study with AMG 650 in adult subjects with locally advanced or metastatic solid tumors with TP53MUT, triple negative breast cancer (TNBC), high grade serous ovarian cancer (HGSOC) or serous like endometrial cancers and other solid tumors. Methods: In this phase 1, multicentric, dose escalation and dose expansion study we evaluate the safety and tolerability of AMG 650 monotherapy in patients with advanced/metastatic solid tumors (NCT04293094). The main objective is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) based on emerging safety, efficacy, and pharmacodynamics (PD) data prior to reaching the MTD. Key inclusion criteria include the presence of measurable disease and diagnosis of advanced/metastatic triple negative breast cancer (TNBC), high-grade serous ovarian cancer (HGSOC), serous-like endometrial cancer or other solid tumors with documented TP53 mutations. In the dose expansion phase, participants with locally advanced or metastatic TNBC or HGSOC will be treated with the preliminary RP2D identified from the dose exploration part of the study. Primary endpoints include the incidence of Dose Limiting Toxicities (DLTs),Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment-related Adverse Events and the evaluation of the number of participants who experience a clinically significant change from baseline in vital signs, electrocardiogram and laboratory tests parameters. Secondary endpoints include Objective Response Rate, Duration of Response, Progression-free Survival, Clinical Benefit Rate, Time to Response, Time to Progression, Overall Survival (OS), Maximum Plasma Concentration (Cmax) of AMG 650, Time to Maximum Plasma Concentration (Tmax) of AMG 650 as well as Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval for AMG 650. Continuous monitoring of toxicity is conducted. The study began enrolling pts in March 2020 and is ongoing. For more information, please contact Amgen Medical Information: medinfo@amgen.com Clinical trial information: NCT04293094.
A single-arm confirmatory study to evaluate the efficacy of nonsurgical therapy for HER2-positive early breast cancer with clinical complete response after primary systemic therapy (JCOG1806: AMATERAS-BC study).
Authors: Fujisawa Tomomi , Shien Tadahiko , Iwata Hiroji , Shigematsu Hideo , Shibata Taro , Sasaki Keita , Takahashi Yuko 
Published: June 2021

TPS601 Background: The surgical treatment is a standard therapy for early breast cancer (EBC) after primary systemic therapy (PST). In more than half of HER2 positive (HER2(+)) breast cancer, pathological complete response (pCR) is achieved by PST with HER2 inhibitors and chemotherapy. In addition, hormone receptor (HR) negative HER2(+) (HR(-)HER2(+)) subtype has higher concordance between pCR and clinical complete response (cCR) before surgery than other subtypes, especially in EBC. However, non-surgical therapy is not an option for EBC with cCR after PST because of few evidence. We planned single arm confirmatory study to evaluate the efficacy and safety of the non-surgical therapy for HR(-)HER2(+) EBC with cCR after PST. Methods: The key eligibility criteria are as follows: 1) Histologically confirmed as invasive ductal carcinoma of breast, HR(-)HER2(+). 2) cT1-2, N0, M0 (UICC 8th). 3) No ipsilateral BC. 4) Women aged 20-74 years. 5) ECOG performance status 0 or 1. 6) Written informed consent. HER2 inhibitors (trastuzumab and pertuzumab) and cytotoxic drugs as PST are administered for all patients (pts). After completion of PST, cCR is diagnosed by breast imaging and physical examination. cCR is defined as 1) Not palpable breast mass by physical examination, 2) No enhanced breast mass by enhanced MRI, 3) No breast mass by sonography. After diagnosis of cCR, conventional radiotherapy for whole breast and boost radiation for tumor bed are mandatory, followed by pertuzumab and trastuzumab every 3 weeks during 9 months. In non-cCR cases, surgical resection is performed and adjuvant therapy are not specified. The primary endpoint is a distant metastasis-free survival (DMFS) at 3 year, the secondary endpoints are DFS, OS, RFS, proportion of local recurrence, and cosmetics outcome. Given that the threshold and expected of DMFS at 3-year is 93% and 98% with a significance level 2.5% (one sided) and 80% power, 170 cCR cases are required. Assuming half of HER2 pts reach to cCR, 350 pts are required as sample size started PST. Enrollment launched January, 2020 and 57 pts are enrolled as of January 12, 2021. Recent reports found that HR positive HER2(+) subtype has higher concordance between pCR and cCR by adding needle biopsy in the diagnosis, so we are planning to include HR positive subtype in this trial. This clinical trial has been registered at Japan Registry of Clinical Trials as jRCTs031190129 and conducted by the Japan Clinical Oncology Group (JCOG) Breast Cancer Study Group under public fund (National Cancer Center Research and Development Fund). Clinical trial information: jRCTs031190129.
A prospective, randomized, multicenter, double-blinded, placebo-controlled phase III trial of the HER2/neu peptide GP2 + GM-CSF versus bacteriostatic saline/WFI placebo as adjuvant therapy after any trastuzumab-based therapy in HER2-positive women with operable breast cancer.
Authors: Patel Snehal , McWilliams David , Fischette Christine T , Thompson Jaye , Daugherty F. Joseph , Osborne C. Kent , Rimawi Mothaffar F. 
Published: June 2021

TPS604 Background: GP2 is a biologic nine amino acid peptide of the HER2/ neu protein delivered in combination with an FDA-approved immunoadjuvant Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF, sargramostim, leukine) that stimulates an immune response targeting HER2/neu expressing cancers. In a prospective, randomized, single-blinded, placebo-controlled, multicenter Phase IIb clinical trial completed in 2018, no recurrences were observed in the HER2/neu positive adjuvant setting after median 5 years of follow-up, if the HLA 2+ patient received the 6 primary intradermal injections over the first 6 months ( p = 0.0338) in a pre-specified subgroup analysis. Furthermore, the GP2 immunotherapy elicited a potent immune response measured by local skin tests and immunological assays. Of the 138 patients that have been treated with GP2 to date over 4 clinical trials, GP2 treatment was well tolerated and no serious adverse events were observed related to the GP2 immunotherapy. This Phase III trial aims to reproduce the Phase IIb study and will explore the use of GP2 + GM-CSF as adjuvant therapy to prevent the recurrence of breast cancer in HER2/neu positive and HLA 2+ patients, post-surgery and following the first year treatment with any trastuzumab-based therapy. Methods: This phase III trial is a prospective, randomized, double-blinded, multi-center study. After 1 year of trastuzumab-based therapy or an approved biosimilar, treatment with GP2 + GM-CSF or placebo (bacteriostatic saline/WFI ) will be administered intradermally for the 6 primary immunization series over the first 6 months and 5 subsequent boosters over the next 2.5 years for a total of 11 injections over 3 years of treatment. The participant duration of the trial will be 3 years treatment plus 2 years follow-up for a total of 5 years following enrollment. An interim analysis is planned and patients will be stratified based on prior and current treatments, among other factors. Eligibility Criteria: The majority of breast cancer patients will be HER2/ neu positive and HLA 2+, disease-free, conventionally treated node-positive, post breast tumor removal surgery and following the first year treatment with trastuzumab-based therapy. Trial Objectives: 1. To determine if GP2 therapy reduces recurrence in HER2/ neu positive breast cancer patients. 2. To monitor the in vitro and in vivo immunologic responses to GP2 therapy and correlate these responses with the clinical outcomes. 3. To monitor for any unexpected adverse events and toxicities related to GP2 therapy. Accrual: The target enrollment is up to approximately 500 patients. Contact information: snehal.patel@greenwichlifesciences.com Funding: This trial is supported by Greenwich LifeSciences.
Phase 3 trial (GCT3013-05) of epcoritamab versus standard of care in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Authors: Thieblemont Catherine , Clausen Michael Roost , Sureda Balari Anna , Zinzani Pier Luigi , Fox Christopher , Kim Su Young , Vindeloev Signe Diness , Lugtenburg Pieternella 
Published: June 2021

TPS7569 Background: Patients (pts) with DLBCL who are refractory to/or have relapsed (R/R) after treatment with chemotherapy and anti-CD20 monoclonal antibody (mAb) have a poor prognosis. There is a need for new treatment options to improve outcomes. Epcoritamab, a novel subcutaneous (SC) bispecific antibody, binds to CD3 on T-lymphocytes and CD20 on B-cell non-Hodgkin lymphoma (NHL) cells to induce potent and selective killing of malignant CD20+ B-cells. In an ongoing phase 1/2 dose-escalation trial in heavily pretreated pts with B-cell NHL (N = 68), epcoritamab demonstrated a tolerable safety profile and substantial single-agent anti-tumor activity, with a complete response (CR) rate of 55% and an overall response rate (ORR) of 91% in pts with R/R DLBCL (at ≥48 mg doses; n = 12) (NCT04663347; Hutchings, ASH, 2020). Furthermore, all 4 evaluable R/R DLBCL pts previously treated with chimeric antigen receptor T-cell (CAR-T) therapy achieved an objective response with 2 achieving CR. These encouraging data support the potential for epcoritamab to improve clinical outcomes in pts with R/R DLBCL. Here we describe the phase 3 trial of epcoritamab versus standard of care (SOC) treatments in pts with R/R DLBCL (NCT04628494). Methods: GCT3013-05 is a randomized, open-label, worldwide, multicenter, phase 3 study designed to evaluate the efficacy of epcoritamab versus investigator’s choice of SOC with R-GemOx (rituximab, gemcitabine, oxaliplatin) or BR (bendamustine, rituximab) in adults with R/R disease of one the following CD20+ B-cell NHL histologies: I) DLBCL, not otherwise specified including de novo DLBCL or DLBCL histologically transformed from follicular lymphoma; II) “double-hit” or “triple-hit” DLBCL (high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 translocations); or III) follicular lymphoma grade 3B. Other key eligibility criteria include: ≥1 line of prior chemotherapy that included treatment with an anti-CD20 mAb, Eastern Cooperative Oncology Group performance status 0–2, and prior failure of/ineligibility for autologous stem cell transplantation. Prior CAR-T therapy is allowed. A total of 480 pts will be randomized 1:1 to receive either SC epcoritamab at the recommended phase 2 dose (28-day cycles; weekly, biweekly, or monthly schedule depending on cycle number) until disease progression or unacceptable toxicity; or up to 4 cycles of biweekly treatment with intravenous (IV) R-GemOx (8 doses); or up to 6 cycles of IV BR (6 doses; dosing every 3 weeks). The primary endpoint is overall survival. Key secondary endpoints include progression-free survival, ORR, duration of response, time to response, and safety. The study is currently enrolling in Australia, Belgium, Denmark, France, Spain, and will open for enrollment in additional countries. Clinical trial information: NCT04628494.
Phase 3 study of pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab with or without olaparib versus concurrent chemoradiation therapy followed by durvalumab in unresectable, locally advanced, stage III non-small cell lung cancer: KEYLYNK-012.
Authors: Jabbour Salma K. , Cho Byoung Chul , Bria Emilio , Kato Terufumi , Bhosle Jaishree , Gainor Justin F. , Reguart Noemi , Wang Luhua , Morgensztern Daniel , Gurary Ellen , Ashraf Tanya B. , Lara-Guerra Humberto , Reck Martin 
Published: June 2021

TPS8580 Background: Pembrolizumab, an anti‒PD-1 antibody is standard of care therapy for metastatic non‒small-cell lung cancer (NSCLC) as monotherapy and in combination with chemotherapy. Durvalumab, an anti–PD-L1 antibody, is approved for unresectable, stage III NSCLC without disease progression following concurrent chemoradiation therapy (CCRT). Early trials of pembrolizumab in combination with chemoradiotherapy, either concurrently or as consolidation, showed acceptable tolerability and promising PFS in patients with unresectable stage III NSCLC. Early data suggest the combination of poly(ADP-ribose) polymerase (PARP) plus anti–PD-(L)1 inhibition can enhance treatment effects. KEYLYNK-012 (NCT04380636) is evaluating pembrolizumab plus CCRT followed by pembrolizumab with/without the PARP inhibitor olaparib vs CCRT followed by durvalumab in patients with unresectable, locally advanced, stage III NSCLC. Methods: This global phase 3, randomized, placebo- and active-controlled, double-blind study is enrolling patients aged ≥18 y with previously untreated, pathologically confirmed, stage IIIA–C NSCLC, an ECOG PS of 0 or 1, and a tumor sample available for PD-L1 evaluation. Patients are randomized 1:1:1 to CCRT (platinum-doublet chemotherapy [cisplatin plus pemetrexed or etoposide; or carboplatin plus paclitaxel] plus radiotherapy 60 Gy over 6 wks [cycles 2–3]) with pembrolizumab 200 mg Q3W (groups A and B) or CCRT alone (group C) for 3 cycles. This is followed by pembrolizumab 200 mg Q3W for 17 cycles plus placebo (group A) or olaparib 300 mg BID (group B); or durvalumab 10 mg/kg Q2W for 26 cycles (group C). Randomization is stratified by disease stage (IIIA vs IIIB/IIIC), tumor histology (squamous vs nonsquamous), PD-L1 tumor proportion score (≥50% vs < 50%) and region (East Asia vs North America/Western Europe/UK vs other). PFS (RECIST v1.1 by blinded independent central review [BICR]) and OS are dual primary endpoints. Secondary endpoints include ORR, duration of response, safety and tolerability, and quality-of-life outcomes. Tumor response will be evaluated per RECIST v1.1 by BICR after CCRT and at regular intervals throughout the study until disease progression, new cancer therapy, study withdrawal, or death. AEs will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Enrollment began July 6, 2020 and is ongoing at 204 sites in 24 countries. Clinical trial information: NCT04380636.
Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC).
Authors: Qin Angel , Kalemkerian Gregory Peter , Patel Jyoti D. , Mohindra Nisha Anjali , Carlisle Jennifer W , Sands Jacob , He Zhicong , Winkler Robert , Liang Zhiyan , Hammock Vakessa , Bombelli Riccardo , Lu Ming , Xu Yang , Fu Tommy , Wang Cunlin , Yang Dajun , Zhai Yifan 
Published: June 2021

TPS8589 Background: Increased expression of BCL-2, BCL-xL, and MCL-1 allows certain tumors to evade apoptosis. Pelcitoclax is a novel, dual BCL-2/BCL-xL inhibitor with strong single-agent antitumor activity against tumor cells addicted to BCL-2, BCL-xL, and BCL-w, and exhibits even broader antitumor activity when administered with chemotherapy. Pelcitoclax reduces tumor growth in SCLC and other human cancer xenograft models, with manageable effects on platelet counts. Preliminary findings from the first-in-human study suggested promising antitumor activity and a favorable safety profile. Methods: This open-label study is evaluating the safety and preliminary efficacy of pelcitoclax combined with paclitaxel in adults with R/R SCLC that has progressed on or after initial treatment. Prior treatments may include platinum-based therapy (± thoracic radiation), immunotherapy, or chemotherapeutic agents other than paclitaxel. Eligible patients have an ECOG performance status of 0-2; adequate organ function; no known bleeding diathesis, immune thrombocytopenic purpura, autoimmune hemolytic anemia, serious gastrointestinal bleeding, or concomitant use of most anticoagulants; and no residual grade ≥ 2 adverse events from previous treatment. In the phase Ib study, the pelcitoclax maximum tolerated dose is being determined using a time-to-event continual reassessment method. In this phase, pelcitoclax is administered by IV infusion over 30 minutes on Days 1, 8, and 15 at dose levels of 80, 160, and 240 mg per week, with fixed-dose paclitaxel 80 mg/m2 on Days 1 and 8 of a 21-day cycle. In addition to a baseline scan within 4 weeks before study entry, computed tomography will be performed every two cycles to evaluate antitumor response. Treatment will continue until disease progression, unacceptable toxicity, consent withdrawal, or administrative discontinuation. The primary endpoint of this phase includes dose-limiting toxicity by NCI CTCAE v5.0 over 21 days. After determination of the recommended phase II dose of pelcitoclax in the phase Ib study, the efficacy of pelcitoclax with paclitaxel will be determined in the phase II study using a Simon two-stage design, with overall response rate as the primary endpoint. Other study endpoints in the phase II study include pharmacokinetics of pelcitoclax with paclitaxel, as well as progression-free and overall survival. As of February 8, 2021, 15 of 58 patients had been enrolled. Internal study identifier APG1252SU101. Clinical trial information: NCT04210037.