bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase III study with atezolizumab versus placebo in patients with malignant pleural mesothelioma after pleurectomy/decortication (AtezoMeso study).
Authors: Pagano Maria , Alloisio Marco , Cappuzzo Federico , Facciolo Francesco , Bironzo Paolo , Pastorino Ugo , Rea Federico , Santoro Armando , Zanelli Francesca , Alberti Giulia , Bonelli Candida , Gervasi Erika , Pinto Carmine 
Published: June 2022

TPS8591 Background: Surgery for malignant pleural mesothelioma (MPM) is indicated mainly in multimodal approaches and in clinical trial settings. Different studies have shown significantly lower complication rates, lower peri-operative morbidity and mortality with pleural/decortication (P/D), with similar overall survival rates. The biology of mesothelioma shows significant heterogeneity. Surgical tumor reduction may create a host environment more amenable to immunotherapy by reducing the ratio of tumor cells versus antitumor effector T lymphocytes, reducing the quantities of intratumor and/or systemic immunosuppressive cells, and ablating tumor-derived paracrine factors that promote local recruitment of immunosuppressive cells. Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T-cell responses against cancer can result in a significant survival benefit. The AtezoMeso Study evaluates the introduction of atezolizumab-ATEZO in MPM, patients (pts) after P/D and platinum/pemetrexed perioperative therapy. Methods: This is a double-blind, placebo controlled, phase III trial, in 20 Italian centers. Main inclusion criteria are P/D without macroscopic residual and ECOG-PS 0-1. Pts who underwent to P/D without macroscopic residual disease and have received at least 4 cycles of perioperative therapy with cisplatin/carboplatin and pemetrexed, will be randomized (2:1) to receive ATEZO or placebo. Therapy will be administered at dose of 1,200 mg iv, every 21 days, for 12 months or until recurrence, unacceptable toxicity or patient/physician decision. Randomization will be done through a centralized system, using histology (epithelioid vs nonepithelioid) and stage (I vs > I) as stratification factors. Pts will be radiologically evaluated after surgical before starting therapy and then every 12 weeks for 24 months or until recurrence. Quality of life (QoL) will be evaluated with the EQ-5D questionnaire administered at baseline and every 12 weeks. Tissue tumor samples will be centrally analyzed to determinate the genomic profile using FoundationOne CDx platform. The primary endpoint is the evaluation of the atezolizumab efficacy in terms of disease free survival (DFS). Secondary endpoints include the safety and efficacy in terms of overall survivall and QoL. Assuming a median DFS equal to 9 months in placebo arm, an accrual time of 24 months and a follow-up time of 24 months, a sample size of 162 pts will allow to detect true hazard ratios of 0.62 with power 0.8, at a confidence level of 95%. At February 14th, 2022, 3 pts have been enrolled. Clinical trial information: 2020-003762-39; GOIRC-02-2019.
Assessing the predictive value of ctDNA on relapse in patients with resected stage IB-IIIA NSCLC treated with adjuvant chemotherapy plus concomitant atezolizumab followed by atezolizumab: BTCRC LUN 19-396.
Authors: Ardeshir-Larijani Fatemeh , Mohindra Nisha Anjali , Traynor Anne M. , Malhotra Jyoti , Shum Elaine , Ma Patrick C. , Hanna Nasser H. 
Published: June 2022

TPS8592 Background: A standard of care treatment for most patients with stage II and III non-small cell lung cancer (NSCLC) and a PD-L1 > 1% is surgery followed by adjuvant (adj) histology-specific chemotherapy followed by 1 year of atezolizumab. The benefit of adding atezolizumab concomitantly to chemotherapy in the adj setting has not been reported. In addition, the optimal duration of adjuvant therapy is undefined. Emerging data have demonstrated the potential for ctDNA to predict clinical recurrence in patients with surgically resected lung, breast, and colon cancer. The current study explores the predictive value of ctDNA for early relapse in patients treated with adj chemotherapy plus atezolizumab. Methods: The LUN19-396 is a phase II biomarker study that enrolls pts with resected NSCLC stage IB (tumors ≥ 4cm), IIA, IIB, and select IIIA (T3N1-2, T4N0-2). The ctDNA will be assessed within 60 days post-surgery and then every 3 months up to 12 months. All pts will receive treatment with 4 cycles of Cisplatin 60-75mg/m2 + Docetaxel 60-75mg/m2 + Atezolizumab 1200mg IV on day 1 q 3w (for patients with squamous cell cancer) or Cisplatin 60-75mg/m2 + Pemetrexed 500mg/m2 + Atezolizumab 1200mg on day 1 IV q 3w (for patients with non-squamous cell), followed by up to 13 additional cycles of Atezolizumab 1200mg IV every 3w. This trial will enroll a total of 100 pts to achieve more than 80% power. The primary objective is to estimate the percentage of pts with detectable ctDNA after surgery who have clearance of ctDNA at designated time points during adjuvant therapy. The key secondary objective is to estimate the 1-year disease-free survival in pts with undetectable ctDNA after 4 cycles of adj chemotherapy plus atezolizumab who had detectable ctDNA after surgery. This trial has enrolled 17 pts as of February 8, 2022. Clinical trial information: NCT04367311.
Phase 3, randomized, placebo-controlled study of stereotactic body radiotherapy (SBRT) with or without pembrolizumab in patients with unresected stage I or II non–small cell lung cancer (NSCLC): KEYNOTE-867.
Authors: Jabbour Salma K. , Houghton Baerin , Robinson Andrew George , Quantin Xavier , Wehler Thomas , Kowalski Dariusz , Ahn Myung-Ju , Erman Mustafa , Giaccone Giuseppe , Borghaei Hossein , McLean Jessica , Xu Yan , Souza Fabricio , Pall Georg 
Published: June 2022

TPS8597 Background: Anti–PD-(L)1-directed therapy following radiotherapy or following concurrent chemoradiation is associated with significantly longer PFS and OS in patients with advanced or metastatic NSCLC, including those with locally advanced inoperable tumors. KEYNOTE-867 (NCT03924869) evaluates the efficacy and safety of SBRT with or without pembrolizumab in patients with unresected stage I or II NSCLC. Methods: In this phase 3, randomized, placebo-controlled study, approximately 530 adult patients with previously untreated, unresected, histologically/cytologically confirmed stage I or II (T1 to limited T3, N0, M0) NSCLC are randomized 1:1 to receive thoracic SBRT to primary tumors for ≤2 wk (Table) and either pembrolizumab 200 mg or placebo every 3 wk for 17 cycles (approximately 1 year) or until disease recurrence, development of unacceptable AEs, SBRT not started for any reason, or study withdrawal. Randomization is stratified by disease stage (I vs II), ECOG PS (0 or 1 vs 2), geographic region (East Asia vs non-East Asia), and reason for not receiving surgery (medically inoperable vs refused surgery). Imaging assessment by blinded independent central review (BICR) occurs at 12 wk (≥10 wk after SBRT completion), followed by every 16 wk for 3 y, and then every 6 mo. Primary endpoints are event-free survival (EFS) by BICR and OS. Secondary endpoints include time to death or distant metastases and safety; exploratory endpoints are time to subsequent treatment, disease-specific survival, and time to recurrence/progression on subsequent line of therapy. AEs are monitored throughout the trial until 30 d after last dose (90 for serious AEs) and graded according to NCI CTCAE version 4.0. EFS and OS are analyzed by the nonparametric Kaplan-Meier method, treatment differences by stratified log-rank test, and hazard ratios by stratified Cox proportional hazard model with Efron's method of tie handling. Enrollment started on June 17, 2019, and is ongoing at 168 sites around the world. Clinical trial information: NCT03924869. [Table: see text]
Combi-TED: A multicenter, phase II, open-label, randomized trial evaluating efficacy of OSE2021 plus docetaxel or OSE2021 plus nivolumab as second-line therapy in metastatic NSCLC progressing after first-line chemo-immunotherapy.
Authors: Cappuzzo Federico , Pasello Giulia , Delmonte Angelo , Landi Lorenza , Benetti Beatrice , Metro Giulio , D'Andrea Mario Rosario , Gori Stefania , Borra Gloria , Mazzoni Francesca , Verusio Claudio , Pagano Maria , Giannarelli Diana , Bonetti Andrea Vincent , Maio Michele , Scimone Antonino , Adamo Vincenzo 
Published: June 2022

TPS9140 Background: First line combination of chemotherapy and immune checkpoint inhibitors (ICIs) improves overall survival (OS) compared with chemotherapy alone in non-small cell lung cancer (NSCLC) patients. However, only few options are available at chemoimmunotherapy failure, with docetaxel representing the standard of care. Tedopi is a cancer vaccine which stimulates killer T cells, currently under development for the therapy of HLA-A2+ lung cancer. In the ATALANTE-1 Phase III trial (EudraCT no. 2015-003183-36), Tedopi provided clinical benefits in patients with advanced NSCLC who failed to respond to checkpoint inhibitors. Given the need for new therapeutic options in patients failing first-line chemo-immunotherapy and the encouraging preliminary data with Tedopi, there is a strong rationale for investigating the activity of Tedopi plus nivolumab or Tedopi plus docetaxel in patients with metastatic NSCLC failing standard first-line therapy. Methods: This is a phase II, non-comparative, randomized multicenter study assessing the combination of Tedopi with docetaxel or nivolumab in NSCLC patients failing after first-line chemoimmunotherapy (EudraCT no. 2020-005170-10). All NSCLC patient candidates for second-line therapy are considered eligible for the study if they are HLA-A2+, with no evidence of EGFR mutations or ALK/ROS1 rearrangement and if they progressed after at least 4 cycles of previous first-line chemo-immunotherapy. Patients are randomly assigned to Tedopi plus docetaxel, Tedopi plus nivolumab (treatment arms) or docetaxel monotherapy (standard arm). The primary endpoint is 1-year OS rate. Secondary endpoints include OS, 2-year OS rate, progression-free survival (PFS), objective response rate (ORR), and safety. An explorative analysis of the correlation of efficacy with several tumor or blood biomarkers (PD-L1 expression, tumor mutational burden, Tedopi neoantigen expression, T cell infiltration), is also performed. Sample size was calculated assuming a 1-year OS rate in the standard arm of 20%. According to the single-stage design, in both treatment arms a 1-year OS rate of 20% would imply that treatment does not warrant further investigation and a 1-year OS rate of 40%, would imply that treatment has a sufficient activity. With a one-sided significance level of 5% and a power of 80%, a total number of 105 patients (35 per treatment arm) need to be enrolled. At the drafting of this abstract, 7 patients have already been enrolled. Total follow-up will be 24 months from last enrolment, for an approximate duration of 48 months. Clinical trial information: NCT04884282.
A phase II randomized, open-labelled, multicenter study of safety and efficacy of combination brigatinib and carboplatin-pemetrexed therapy or brigatinib monotherapy as first-line treatment in patients with advanced ALK-positive non–small cell lung cancer (IFCT-2101 MASTERPROTOCOL ALK).
Authors: Duruisseaux Michaël , Swalduz Aurélie , Mazieres Julien , Barlesi Fabrice , Amour Elodie , Morin Franck , Westeel Virginie 
Published: June 2022

TPS9144 Background: Second generation ALK tyrosine kinase inhibitors (ALK-TKI), including brigatinib, provide substantial therapeutic benefit in first-line treatment of ALK-positive NSCLC patients (pts) but relapse eventually occurs in all pts due to development of drug resistance, possibly caused by emergence of drug-tolerant cells (DTC). Combining chemotherapy to TKI may prevent DTC emergence in preclinical studies, and results in prolonged progression-free survival (PFS) and overall survival in EGFR-mutant NSCLC. We hypothesize that combination of second generation ALK-TKI with chemotherapy will improve clinical outcomes in advanced ALK-positive NSCLC patients. The IFCT-2101 MASTERPROTOCOL ALK trial will evaluate the efficacy and safety of brigatinib and carboplatin-pemetrexed combination in treatment-naïve metastatic ALK-positive NSCLC. Methods: The IFCT-2101 MASTERPROTOCOL ALK randomized, open-label phase II trial will enrol 110 pts in 30 French centers over 24 months. Eligible pts will have metastatic NSCLC with ALK-fusion according to local testing, be untreated for advanced disease, and have an ECOG Performance Status (PS) of 0-1 and at least one measurable lesion per RECIST 1.1. Pts with asymptomatic and stable brain metastases (BM) will be eligible. Exclusion criteria include leptomeningeal metastases. Patients will be randomized 1:1 to receive brigatinib monotherapy (Arm A) or combination brigatinib and carboplatin-pemetrexed therapy (Arm B), with PS (0 vs 1) and BM (presence vs absence) as stratification factors. Brigatinib will be administered at a dose of 90 mg QD for a 7-day lead-in period followed by 180 mg QD continuously, in 28-day cycles. In Arm B, 4 cycles of carboplatin (AUC 5) and pemetrexed (500 mg/m2) therapy every 3 weeks will be added at Day 8 of brigatinib treatment. Treatment will continue until progression, intolerable toxicity or discontinuation. The first 26 pts enrolled in Arm B will represent the population of a safety phase, during which adverse events (AE) will be closely monitored by an independent data monitoring committee. The primary endpoint is investigator-assessed 12-month PFS rate. Secondary endpoints include independently-reviewed 12-month PFS rate, overall response rate (ORR), 12-month intracranial PFS and ORR, incidence, nature and severity of AEs, and impact of ALK-fusion detection, co-mutations and clearance of circulating tumor (ct) DNA (Guardant360) on outcome. Exploratory objectives include the evaluation of early blood ctDNA decrease on patient outcome. The study is enrolling and primary completion date is March 2025. Clinical trial information: NCT05200481.
EVOKE-01: A phase 3 study of sacituzumab govitecan (SG) versus docetaxel in patients with non–small cell lung cancer (NSCLC) progressing on or after platinum-based chemotherapy and checkpoint inhibitors.
Authors: Garassino Marina Chiara , Reznick Douglas , Liu Steven Y. , Reinmuth Niels , Girard Nicolas , de Marinis Filippo , Mekan Sabeen Fatima , Patel Riddhi , Ding Michelle , Paz-Ares Luis 
Published: June 2022

TPS9149 Background: Single-agent chemotherapy, such as docetaxel, is the standard of care in patients with metastatic NSCLC who progressed on platinum-based therapy and checkpoint inhibitors. However, docetaxel is associated with poor survival (median overall survival [OS] of < 1 year); thus, novel agents are needed to further improve outcomes in this setting. SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. In a single-arm expansion of the phase 1/2 IMMU-132-01 basket study of advanced epithelial cancers (NCT01631552), SG demonstrated an objective response rate (ORR) of 17% and median OS of 9.5 months, with a manageable safety profile in 54 patients with metastatic NSCLC who had multiple prior therapies (Heist RS, et al. J Clin Oncol. 2017). EVOKE-01 randomized phase 3 study was designed to further evaluate SG in patients with metastatic NSCLC. Methods: EVOKE-01 (NCT05089734) is an open-label, global, multicenter, randomized, phase 3 study comparing the efficacy and safety of SG vs docetaxel in patients with metastatic NSCLC. Key eligibility criteria include age ≥18 years, pathologically documented stage IV NSCLC at time of study entry, and progression after platinum-based chemotherapy and anti-PD(L)1 therapy given either in combination or sequentially. Patients with EGFR, ALK, or other known actionable genomic alterations must have also received treatment with ≥1 approved appropriate TKI. Other inclusion criteria are ECOG performance status 0-1 and adequate hematologic, hepatic, and renal function. Patients with prior treatment with topoisomerase inhibitors are excluded. Patients are randomized 1:1 to receive intravenous SG (10 mg/kg on day 1 and 8) or docetaxel (75 mg/m2 on day 1) in 21-day cycles until progressive disease or unacceptable toxicity. Stratification is based on predominant histology (squamous vs nonsquamous), best response to prior immune therapy (PD/SD vs CR/PR), and prior therapy for actionable genomic alteration (yes vs no). The primary endpoint is OS. Key secondary endpoints include progression-free survival, ORR, duration of response, and disease control rate, as assessed by investigator RECIST v1.1, mean change from baseline in NSCLC-SAQ total score and shortness of breath, and safety. This study plans to enroll ̃520 patients globally and is open for recruitment. Clinical trial information: NCT05089734.
ATTAC-MCC: Phase I/II study of autologous CD8+ and CD4+ transgenic T cells expressing a high affinity MCPyV-specific TCR combined with checkpoint inhibitors and class I MHC-upregulation in patients with metastatic MCC refractory to PD-1 axis blockade.
Authors: Veatch Joshua , Akkiraju Ananth , Darwanto Agus , Garrity Sean , Hallet Damien , Nguyen Kim , Pierog Piotr , Sewastianik Tomasz , Vallaster Markus P , Vincent Loic , Chapuis Aude 
Published: June 2022

TPS9596 Background: Merkel cell carcinoma (MCC) is a highly aggressive skin cancer, with an incidence that has doubled in the last 20 years to approximately 3000 cases/year in the US. Over one-third of patients will develop widespread disease, and survival in these patients has been historically poor with a 5-year survival rate of < 10%. MCC is highly immune-sensitive due to the antigenicity of the cancer-causing Merkel cell polyomavirus (MCPyV) expressed in most MCC tumors. Although immune checkpoint inhibitors (ICIs) targeting the PD-(L)1 axis show promising efficacy, most MCC patients will eventually relapse. There is no standard of care for patients that become refractory to ICIs. We hypothesize that cellular immune therapies targeting MCPyV may provide additional clinical benefit to these patients. To test this, we have engineered high-affinity TCR T cells against MCPyV and initiated a clinical trial. Methods: NCT03747484 is an ongoing phase I/II, open label, investigator-initiated trial (IIT) of FH-MCVA2TCR in combination with an anti-PD-(L)1 checkpoint inhibitor and an agent to upregulate MHC-I expression on tumor cells. The trial is conducted in patients aged 18 years or older with metastatic or unresectable, histologically confirmed virus-positive MCC whose disease has progressed on or after treatment with a PD-(L)1 axis checkpoint inhibitor. Patients undergo leukapheresis to collect white blood cells (WBCs) for TCR T cell product manufacturing. The cell product is administered on day 0. Patients receive an agent to upregulate MHC-I on tumor cells and continue on an anti-PD-(L)1 checkpoint inhibitor for up to one year. In phase I, three patients receive up to two infusions of dose level 1 of the T cell product. The primary objectives of phase I are to determine safety and tolerability based on dose-limiting toxicities (DLT) during an observation period of 28 days after the first infusion. Phase II enrolls patients at dose level 2. The total sample size of phase II is 12 patients. The first three patients are enrolled in a staggered manner and observed for DLTs. If no DLTs occur, the remaining sample size is accrued in open enrollment. The main objectives of phase II are safety based on number of adverse events and preliminary efficacy based on tumor response according to RECISTv1.1 and iRECIST. Secondary/exploratory objectives include cellular kinetics of TCR T cells, T cell phenotype, tumor infiltration kinetics, and MHC-I expression dynamics over time. After the first 12 months, patients transition to a long-term follow-up (LTFU) study for up to 15 years as per FDA guidelines. Clinical trial information: NCT03747484.
Evaluating the impact of perioperative antibiotic prophylaxis on the microbiome in patients with cutaneous malignancy.
Authors: Cass Samuel , Witt Russell G. , Meng Xialong , Sahasrabhojane Pranoti , Bassett Roland L. , Shelburne Samuel , Chang Hsiu Yin , Somaiya Kinjal , Mungovan Kristi , Fisher Sarah B. , Lucci Anthony , Lee Jeffrey Edwin , Ross Merrick I. , Gershenwald Jeffrey E. , Duncan Sheila , Ajami Nadim J. , Roland Christina Lynn , Wargo Jennifer Ann , Keung Emily Zhi-Yun 
Published: June 2022

TPS9602 Background: Preoperative antibiotic prophylaxis is commonly used to reduce surgical site infections (SSIs). However, the rate of SSIs following surgical procedures classified as clean is only 2-3%. Overuse of antibiotics is associated with several potential adverse effects, including dysregulation of the gut microbiome. Disruption of the composition and function of the native gut microbiota, referred to as dysbiosis, has been implicated in a number of inflammatory and autoimmune disorders, as well as gastrointestinal (GI) and non-GI cancers. Recent studies have demonstrated that antibiotics have a profound and persistent effect on the gut microbiota, as evidenced by diminished overall abundance and diversity, as well as alteration of community composition that includes a decreased relative abundance of bacteria in the Ruminococcaceae family. In melanoma, diversity of gut microbiota and relative abundance of Ruminococaceae have been linked to improved survival and enhanced response following immune checkpoint blockade. In this study, we seek to determine the impact of preoperative prophylactic antibiotic use on the gut microbiome in patients following surgery for stage I or II melanoma. Methods: In this non-comparative randomized pilot trial, the impact of prophylactic antibiotic use at the time of surgical intervention on gut microbiome diversity and composition will be studied. Patients diagnosed with clinical stage I or II melanoma undergoing wide excision with or without lymphatic mapping and sentinel lymph node biopsy are randomized 1:1 to either receive preoperative cefazolin or no preoperative antibiotics. Stool samples and peripheral blood are collected before surgery, the day of surgery (optional), on post-operative day 3 (optional), and 2 weeks and 3 months following surgery. The primary endpoint for the study is change in microbiome alpha diversity at 2 weeks following surgery. Secondary endpoints are change in relative abundance of microbes at 2 weeks and 3 months after surgery and SSI rates according to whether or not prophylactic antibiotics were administered at time of surgery. Exclusion criteria include recent antibiotic use (within 3 months), allergy to beta-lactam or cephalosporin antibiotics, increased risk of infection due to medical comorbidity or use of immunosuppressive medication. Enrollment began in October 2021. As of January 2022, 22 of 30 patients have been accrued to ensure complete sample collection for 20 patients. Study findings may inform a larger trial evaluating interventions to mitigate antibiotic impact. Clinical trial information: NCT04875728.