bluuebunny/crossref_metadata_2025_split huggingface dataset:
BEGONIA: Phase 1b/2, open-label, platform study of the safety and efficacy of durvalumab (D) ± paclitaxel (P) with novel oncology therapies for first-line metastatic triple-negative breast cancer (mTNBC): Addition of arm 7, D + datopotamab deruxtecan (Dato-DXd; DS-1062).
Authors: Schmid Peter , Nunes Ana Tablante , Dry Hannah , Dougherty Rachel , Karwe Vatsala , Scheuring Urban J. 
Published: June 2021

TPS1105 Background: Patients (pts) with mTNBC have limited treatment options and poor prognosis. The combination of immune checkpoint inhibitors with chemotherapy shows promise, but only a subset of pts with mTNBC derive benefit, highlighting the need for new combinations. BEGONIA is an ongoing Simon 2-stage, multicenter, multi-arm platform study evaluating the safety and efficacy of D, an anti–PD-L1 monoclonal antibody, with or without P, in combination with novel oncology therapies as first-line treatment for mTNBC (NCT03742102). Dato-DXd is an antibody-drug conjugate (ADC) consisting of a humanized anti-trophoblast cell surface antigen 2 (TROP2) IgG1 monoclonal antibody, a stable tetrapeptide-based cleavable linker, and a topoisomerase I inhibitor payload. Dato-DXd displayed encouraging clinical activity with a manageable safety profile in heavily pretreated pts with metastatic NSCLC in the phase 1 TROPION-PanTumor01 (NCT03401385) study. TROP2 is highly expressed on breast and other epithelial tumors, and a TROP2 ADC showed activity in heavily pretreated pts with mTNBC (Bardia, NEJM 2019). Methods: Eligible female pts are aged ≥18 years with untreated unresectable, locally advanced or mTNBC, ≥12 months since prior taxane therapy, ECOG PS 0/1, adequate organ function, and ≥1 nonirradiated measurable lesion. For Arm 7, pts are excluded if they have clinically significant corneal disease, history of interstitial lung disease/pneumonitis, underlying pulmonary disorder, or prior treatment with an ADC containing a topoisomerase I inhibitor. Arm 7 will evaluate D (1120 mg) + Dato-DXd (6 mg/kg) given intravenously every 3 weeks until disease progression or unacceptable toxicity. Part 1 of each arm includes a total of 30 pts with a safety run-in (n=6) to observe dose-limiting toxicities, identify the recommended phase 2 dose (RP2D), and detect an efficacy signal for part 1 expansion. The primary endpoint of part 1 is safety and tolerability. Secondary endpoints include investigator-assessed objective response rate (ORR), duration of response, progression-free survival (PFS), and overall survival (OS). Once the RP2D has been established for part 1, a futility analysis will be performed with an option to expand the cohort to an additional 27 pts if expansion criteria are met. The primary endpoint for part 1 is ORR. Tumors will be assessed every 6 weeks per RECIST v1.1. Kaplan-Meier analysis will be used for PFS and OS. PD-L1 and TROP2 expression will be assessed by immunohistochemistry. Enrollment is ongoing. Clinical trial information: NCT03742102 .
Investigating bacterial decolonization for the prevention of radiation dermatitis: A randomized controlled trial and quality of life assessment.
Authors: Mieczkowska Karolina , Deutsch Alana , Shinoda Kosaku , Daily Johanna , Ohri Nitin , McLellan Beth 
Published: June 2021

TPS12137 Background: Radiation dermatitis (RD) can be therapy-limiting and detrimental to quality of life for cancer patients receiving radiation therapy (RT). Bacteria play an important role in many inflammatory dermatoses. In an observational clinical study, our group discovered that nasal colonization with bacteria, specifically with Staphylococcus aureus (SA), prior to RT was an independent predictor of higher-grade RD (grade ≥2). Higher-grade RD patients were also found to have more SA on the irradiated skin after treatment. If successful, bacterial decolonization could be a safe and cost-effective method to prevent RD. Methods: This is a randomized controlled trial assessing the efficacy of universal bacterial decolonization in preventing RD. Subject inclusion criteria include patients who are aged ≥ 18 years with a diagnosis of a solid tumor of the breast or head and neck with plans for fractionated RT (≥ 15 fractions) with curative intent. Based on previous studies and power analyses, we plan to recruit a total of 80 patients. Patients in the control arm will be treated according to standard of care, including daily application of emollients and gentle bathing. In addition to standard of care, patients in the intervention arm will receive a decolonization regimen consisting of intranasal mupirocin ointment used twice daily and chlorhexidine wash used daily for 5 days prior to the initiation of RT and repeated for 5 days every other week throughout RT. Study evaluations for both groups will include bacterial cultures obtained via superficial swab from the nares, irradiated skin, and contralateral non-radiated skin performed at the beginning, middle, and end of RT. Additionally, standardized photographs of the skin at the radiated site will be performed prior to and at the completion of RT, which will be graded by a dermatologist blinded to study arm. Lastly, at identical timepoints, each patient will complete the SKINDEX-16 questionnaire, a validated quality of life (QoL) assessment. The primary endpoint is development of grade ≥ 2 RD, as compared to low-grade RD (grade 0-1), during RT. The secondary endpoint includes the impact of bacterial decolonization on QoL. Pearson’s chi square or Fisher’s exact tests will be used to compare the incidence rates of higher-grade RD between the interventional arm and control arm to assess if the intervention is associated with a lower incidence rate of higher-grade RD. Paired t-tests will be used to compare the QoL score change from baseline to after RT between the two arms. Linear regression models will be used in both analyses to adjust for covariates. Clinical trial information: NCT03883828.
A study evaluating targeted therapies in participants who have advanced solid tumors with genomic alterations or protein expression patterns predictive of response (MyTACTIC).
Authors: Grothey Axel , Howland Michael , Hubbard Lloryn , Szado Tania , McDonald Anne , Darbonne Walter C. , Levy Jonathan , Borden Eucharia , Spigel David R. , Vanderwalde Ari M. , Schwartzberg Lee S. 
Published: June 2021

TPS1588 Background: Cancer treatment is evolving toward a more personalized approach in which the intersection of genomics, pathology and imaging methods leads to individualized care. Furthermore, identification of novel genomic alterations and other biomarkers has the potential to lead to customized, targeted treatments. Matching specific therapies to tumor biomarkers has the potential to yield valuable clinical information. Here we present a multiarm basket trial that matches patients with a broad array of metastatic solid cancers to investigational therapies alone or in combination based on specific, targetable genomic alterations or protein expression patterns that are potentially predictive of response (MyTACTIC). Historically, such trials have been conducted at large academic medical centers rather than community centers, where most US patients with cancer receive treatment. Prioritizing community centers for this study presents an exciting opportunity to generate data from a more representative patient population. Methods: This phase II, multicenter, nonrandomized, open-label study is enrolling approximately 200 participants with advanced solid tumors that harbor alterations including mutations, fusions, amplifications and protein loss in specific biomarkers that include human epidermal growth factor receptor 2 (HER2), phosphoinositide 3-kinase (PI3K), anaplastic lymphoma kinase (ALK), proto-oncogene tyrosine-protein kinase (ROS1), protein kinase B (AKT), phosphatase and tensin homolog (PTEN), high tumor mutational burden (TMB), high microsatellite instability (MSI) and deficient mismatch repair (dMMR). Patients aged ≥18 years with positive local biomarker results from tissue or blood samples will be enrolled from community oncology centers and practices. Eligibility criteria have been broadened to allow enrollment of a diverse population of patients, including those with nonmeasurable disease, HIV or viral hepatitis infections, and to allow for previous treatment with anticancer agents in the same class. Once general and arm-specific criteria are met, patients will be assigned to 1 of 10 treatment arms to receive mono- or combination therapy with targeted agents, immunotherapy and/or chemotherapy (≤25 patients per arm). The primary objective is to evaluate confirmed objective response rate, as assessed by the investigator according to RECIST version 1.1 or RANO criteria for primary central nervous system tumors. Progression-free survival, duration of response, overall survival and safety will also be assessed. Special attention has been paid to the study design and implementation to ensure equitable access, along with flexibility to add additional baskets. Enrollment is ongoing. Clinical trial information: NCT04632992.
Combination of atezolizumab and pirfenidone in second-line and beyond NSCLC: A phase I/II study.
Authors: Komiya Takefumi , Zhang Jun , Neupane Prakash C. , Mehta Kathan , Huang Chao Hui 
Published: June 2021

TPS2678 Background: Checkpoint inhibitors (CPI) targeting the PD1/PD-L1 axis significantly improved patient outcomes in stage IV non-small cell lung cancer (NSCLC). However, these patients will eventually develop resistance and progression. There is a need to identify novel treatment options. Poor response to PD-L1 antibody was correlated with increase in cancer-associated fibroblasts (CAF), which is known to interact with cytotoxic T cells (CTLs) by suppressing their function in a manner similar to regulatory T cells (Tregs). Production of cytokines by CAFs leads to impaired antitumor immunity by impairing CTL function (TGF beta) and prevent recruitment/mobilization of CTLs into tumors. These effects suggesting that CAF can be a therapeutic target in lung cancer resistant to checkpoint inhibitors. Pirfenidone (P) is approved to treat pulmonary fibrosis with anti-fibrotic effect by blocking the differentiation of fibroblasts into CAFs and suppress the production of TGF beta and TGF beta-induced signaling pathways/collagens. Atezolizumab is a humanized immunoglobulin (Ig) G1 monoclonal antibody that targets PD-L1 and inhibits the interaction between PD-L1 and its receptors, PD-1 and B7-1 (CD80), both of which function as inhibitory receptors expressed on T cells. We proposed a phase I/II trial to test the combination of atezolizumab (A) with P in patients with recurrent non-small cell lung cancer (NSCLC) after progression with CPI. The primary objective of phase I is to determine the maximum tolerated (MTD) dose of P in combination with A and assess the safety and tolerability of this combination. The secondary objective is to determine the efficacy of AP in all NSCLC participants treated in this study. Exploratory objectives include the measurement of circulating levels of TGF beta and research in expression of CAF related proteins. Methods: The initial phase I will enroll 3 patients using P at 801 mg po TID. A will be at 1200mg iv every 3 weeks. If there is ≤ 1 DLT, the study will proceed to phase II If there are 2- 3 DLT, P will be reduced to 534 mg TID. If there is ≤ 1 DLT, then this dose will proceed to phase II. If there is 2-3 DLT, then the study will be terminated. The phase II will enroll 16 patients to assess efficacy. Main inclusion criteria are patients with recurrent NSCLC after progression with first-line therapy CPI with or without chemotherapy, measurable disease, ECOG 0-2, and adequate organ function. Clinical trial information: NCT04467723.
A phase 1 study of SGN-B6A, an antibody-drug conjugate targeting integrin beta-6, in patients with advanced solid tumors (SGNB6A-001, Trial in Progress).
Authors: Patnaik Amita , Calvo Emiliano , Piha-Paul Sarina Anne Anne , Hollebecque Antoine , Galvao Vladimir , Lopez Juanita Suzanne , Braiteh Fadi S. , Sanborn Rachel E. , Zhou Peigen , Nazarenko Natalya N. , Dowlati Afshin 
Published: June 2021

TPS3144 Background: The extracellular matrix (ECM) plays an important role in solid tumor pathogenesis and is a major focus of research and therapeutic targeting. Integrin beta-6 is a cell surface receptor that interacts with the ECM to mediate cellular adhesion. Integrin beta-6 is overexpressed in numerous solid tumors and its expression is a negative prognostic marker in cancers including colorectal, non-small cell lung, gastric, and cervical cancers. SGN-B6A is an investigational vedotin, an antibody-drug conjugate directed against integrin beta-6 to selectively deliver the cytotoxic agent monomethyl auristatin E, which binds tubulin and induces apoptosis. In multiple xenograft models, treatment with SGN-B6A resulted in tumor growth delay and regression in tumor volume when compared to non-binding control. Methods: SGNB6A-001 (NCT04389632) is a phase 1, first-in-human, open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-B6A in adults with select advanced solid tumors. Primary objectives are to evaluate the safety and tolerability of SGN-B6A in patients with advanced solid tumors, identify the maximum tolerated dose, and identify a recommended dose and schedule. The study has 2 parts: dose escalation (Part A) and dose expansion with multiple disease-specific cohorts and a biology cohort (Part B). SGN-B6A will initially be given by intravenous infusion on Days 1, 8, and 15 of 21-day cycles. The dose escalation (Part A) will be conducted using the modified toxicity probability interval method to determine a dose that demonstrates a dose-limiting toxicity rate of 25% with a 5% margin. The dose and schedule for Part B will be determined based on evaluation of safety, PK, and pharmacodynamic biomarkers. Response evaluations will be based on RECIST v1.1. Patients must be ≥18 years old and have histologically or cytologically confirmed metastatic or unresectable solid malignancy within one of the following tumor types: non-small cell lung cancer, head and neck squamous cell cancer, breast cancer, esophageal cancer, ovarian cancer, cutaneous squamous cell cancer, exocrine pancreatic adenocarcinoma, bladder cancer, cervical cancer, or gastric cancer. After an appropriate dose and schedule are determined in Part A, safety and preliminary antitumor efficacy of SGN-B6A will be evaluated in indication-specific cohorts (Part B). This study is ongoing in sites across North America and Europe. Clinical trial information: NCT04389632.
A multicenter open-label phase 1 study evaluating the safety and tolerability of HMPL-306 in patients with locally advanced or metastatic solid tumors with IDH mutations.
Authors: Janku Filip , Kauh John S. , Tucci Christopher , Yang Zhao , Kania Marek K. , Alese Olatunji B. 
Published: June 2021

TPS3159 Background: Isocitrate dehydrogenase (IDH) is a rate-limiting tricarboxylic acid cycle enzyme with 3 isoforms. Mutations in IDH1 and IDH2 result in gain-of-function activity that can cause tumor formation and/or progression and have been associated with various tumor types. Therefore, selective, single mutant IDH (mIDH) isotype inhibitors (mIDH1 or mIDH2) can lead to insufficient efficacy and the potential for tumor resistance. HMPL-306 is an innovative, small-molecule, orally available, highly selective, potent inhibitor of both mIDH1 and mIDH2. Clinical development of a compound that concurrently targets, inhibits, and suppresses multiple mIDHs could lead to significant and durable clinical benefit for patients (pts) with solid tumors harboring IDH mutations. Methods: This is a phase 1, open-label, dose escalation (Part 1) and dose expansion (Part 2) study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of HMPL-306 in pts ≥18 years with locally advanced or metastatic solid tumors with any IDH mutations. HMPL-306 will be administered orally, once daily in a 28-day continuous dosing treatment cycle. The HMPL-306 dose will be escalated in Part 1 according to the modified toxicity probability interval-2 (mTPI-2) design in 4 cohorts in approximately 15-20 pts: 50, 100, 150, and 200 mg. Eligible pts must have locally advanced or metastatic solid tumors with IDH1 or IDH2 mutations. The primary objectives are to evaluate safety, dose limiting toxicities (DLTs), tolerability, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and PK. Approximately 95 pts will be enrolled at the RP2D in Part 2 to further characterize the safety, tolerability, PK, PD, and preliminary anti-tumor activities of HMPL-306. Part 2 will include 5 dose expansion cohorts: cholangiocarcinoma (n = 20), skeletal chondrosarcoma (n = 20), low-grade glioma (n = 20), perioperative low-grade glioma (n = 15), any other solid tumor harboring an IDH1/2 mutation (n = 20). All pts will continue treatment until disease progression, unacceptable toxicity, withdrawal of consent, or at the investigator’s discretion. Safety will be assessed based on reports of adverse events including clinical laboratory testing, vital signs, physical examinations, and electrocardiograms. All pts who receive any study treatment will be included in safety and efficacy analyses. Antitumor activity based on investigator-assessed overall response will be evaluated using descriptive analyses. Objective response rate will be calculated with 95% confidence interval using the Clopper-Pearson method. The Kaplan-Meier method will be used to summarize the time-to-event data such as progression-free survival and duration of response. No statistical hypothesis testing is planned. Enrollment started February 2021.
Neoadjuvant chemoradiotherapy with sequential ipilimumab and nivolumab in rectal cancer (CHINOREC): A prospective randomized, open-label, multicenter, phase II clinical trial.
Authors: Laengle Johannes , Kuehrer Irene , Pils Dietmar , Kabiljo Julijan , Stift Judith , Herbst Friedrich , Dauser Bernhard , Monschein Matthias , Razek Peter , Haegele Stefanie , Huller Wolfgang , Fuegger Reinhold , Geinitz Hans , Petzer Andreas L. , Bitterman Clemens , Laengle Friedrich , Tamandl Dietmar , Widder Joachim , Schmid Rainer , Bergmann Michael 
Published: June 2021

TPS3623 Background: Immune checkpoint inhibitors (ICI), such as ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) or nivolumab (anti-programmed cell death protein 1) have been proven to be an effective strategy in solid cancers. However, ICI seem not to be effective in microsatellite stable (MSS) cancers. As they might lack an immunogenic priming, radiotherapy (RT) is capable to induce an immunogenic cell death (ICD) and subsequently an immunogenic tumor immune microenvironment (TIME). Thus, RT might restore the susceptibility of MSS tumors to ICI and consequently leading to an effective anti-tumor immune response. Methods: This is a prospective, randomized, open-label, multicenter, phase II investigator-initiated clinical trial (IIT), including patients with locally advanced rectal cancer (LARC). Patients receive either neoadjuvant chemoradiotherapy (CRT) alone (50 Gy in 2 Gy fractions over 25 working days + capecitabine 1650 mg/m2/d PO) or in combination with ipilimumab (1 mg/kg IV on day 7) and nivolumab (3 mg/kg IV on day 14, 28 and 42). Patients will undergo surgery within 10-12 weeks post CRT. The primary endpoint is incidence of treatment-emergent adverse events (AEs) assessed by the Clavien-Dindo classification of surgical complications and the common terminology criteria of adverse events (CTCAE). Secondary objectives are radiographic and pathological therapy response. Serial liquid (plasma, serum and peripheral blood mononuclear cells) and tissue biopsies will be taken before, during and after neoadjuvant treatment. Genomic, transcriptomic, epigenomic and proteomic pattern of liquid and tissue biopsies, as well as the immune cell infiltrate of resected specimen, will be correlated with therapy response and clinical outcome. Currently 8 of planned 80 patients have been enrolled. Registration numbers: NCT no. NCT04124601, EudraCT no. 2019-003865-17. Clinical trial information: NCT04124601.
AdvanTIG-203: A randomized phase 2 study comparing anti-TIGIT ociperlimab plus tislelizumab versus tislelizumab plus placebo as second-line treatment in patients with advanced or recurrent esophageal squamous cell carcinoma (ESCC) expressing programmed death-ligand 1 (PD-L1).
Authors: Xu Rui-hua , Kim Sung-Bae , Tougeron David , Zuo Yunxia , Yang Haiyuan , Zhang Juan , Shi Jingwen , Van Cutsem Eric 
Published: June 2021

TPS4150 Background: The programmed death-1 (PD-1)/PD-L1 pathway plays an important role in tumor induced immunosuppression. PD-L1 overexpression is observed in approximately 30–60% of esophageal cancers and is associated with poor prognosis. Anti-PD-1 agents demonstrate moderate efficacy in PD-L1-positive esophageal cancer in terms of response rate and overall survival, however, long-term outcomes remain poor due to primary and secondary resistance driven by tumor immune escape. The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) is upregulated on T-cells and natural killer cells in multiple solid tumors, which can inhibit anticancer immune responses. Ociperlimab (BGB-A1217) is a novel, humanized, monoclonal antibody that binds TIGIT with high specificity and affinity, blocking the interaction with its ligands on tumor cells. Preclinical and clinical studies suggest that dual targeting with anti-TIGIT and anti-PD-1 antibodies produces synergistic immune cell activation and enhanced antitumor activity. Methods: AdvanTIG-203 is a phase 2, global, randomized, double-blind, placebo-controlled study (NCT04732494) of patients with unresectable, locally advanced, recurrent or metastatic ESCC, who progressed on or after 1st line systemic therapy and whose tumors express PD-L1 (visually estimated combined positive score ≥10%). After stratification by Eastern Cooperative Oncology Group performance status (0 or 1), number of metastatic sites (≤1 or ≥2) and region (Asian or non-Asian), 280 patients will be randomized (1:1) to either ociperlimab 900 mg intravenous (IV) plus tislelizumab 200 mg IV every 3 weeks (Q3W), or tislelizumab plus placebo Q3W, until disease progression (per RECIST v1.1), unacceptable toxicity, death or withdrawal of consent. Co-primary endpoints are investigator-assessed overall response rate (ORR) and overall survival (OS) in the intention-to-treat population. A sample size of 280 patients was estimated to provide approximately 94.8% power to detect a 20% difference in ORR at a one-sided significance level of 0.025. With 198 deaths, the study was estimated to provide approximately 86% power to detect a hazard ratio of 0.65 for OS. Secondary endpoints are ORR by independent review, progression-free survival, duration of response, disease control rate, and clinical benefit rate per investigator and independent assessment, cancer-specific health-related quality of life (HRQoL), and safety. Exploratory endpoints include but are not limited to expression of TIGIT, CD226, CD155, CD112, and PD-L1, pharmacokinetics, immunogenicity, and generic HRQoL measures. Clinical trial information: NCT04732494.