bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 study to assess the efficacy, safety, and tolerability of the GDF-15 inhibitor ponsegromab in patients with cancer cachexia.
Authors: Crawford Jeffrey , Lubaczewski Shannon L , Tarachandani Anil , Harrington Magdalena A , Weng Yan , Qiu Ruolun , Collins Susie M , Rossulek Michelle I , Revkin James H 
Published: June 2023

TPS12147 Background: Cancer cachexia is a multifactorial metabolic syndrome of wasting characterized by anorexia, unintended weight loss, and decreased skeletal muscle mass, leading to progressive functional impairment, fatigue, diminished quality of life, poor response to anticancer therapy, and reduced survival. One of the biomarkers associated with cancer cachexia is cytokine growth differentiation factor 15 (GDF-15), which is secreted by tumor cells. Preliminary phase 1 data suggest that suppression of GDF-15 may lead to improvement in cachexia-related symptom burden. Ponsegromab is a potent and selective humanized monoclonal antibody that inhibits GDF-15-mediated signaling. The primary objective of this study (NCT05546476) is to assess the effect of ponsegromab on body weight in patients with cancer, cachexia, and elevated circulating GDF-15 concentrations. Secondary objectives include assessing physical activity, gait, anorexia/appetite, nausea and vomiting, fatigue, and safety. Exploratory objectives include evaluating pharmacokinetics, pharmacodynamics, and immunogenicity. Methods: This phase 2 study will enroll approximately 168 adults with non–small cell lung, pancreatic, or colorectal cancers who have cachexia and elevated GDF-15 concentrations. The study will be conducted in 2 parts. The initial 12-week treatment period will be a randomized, double-blind, placebo-controlled study wherein participants who meet eligibility criteria will be randomized 1:1:1:1 to one of 3 dose groups of ponsegromab (administered subcutaneously [SC] every 4 weeks [Q4W]) or placebo. The double-blind period will be followed by optional open-label treatment (OLT) with ponsegromab Q4W SC for up to 1 year. Upon completion of the optional OLT period, there will be a follow-up visit at Week 72. Participants who do not proceed with the optional OLT period will complete the Week 12 visit and a follow-up visit at Week 16. The primary endpoint is the mean change from baseline in body weight at Week 12. A mixed model for repeated measures followed by a Bayesian Emax model will be used for the primary analysis. Secondary endpoints include physical activity and gait measured by remote digital sensors; patient-reported appetite-related symptoms assessed by Functional Assessment of Anorexia-Cachexia Therapy scores; anorexia/appetite, nausea, vomiting, and fatigue evaluated according to questions from the Cancer-related Cachexia Symptom Diary; and incidence of adverse events, safety laboratory tests, vital signs, and electrocardiogram abnormalities. © 2023 American Association for Cancer Research®. Reused with permission. Clinical trial information: NCT05546476 .
Study for the prevention of oral mucositis.
Authors: Oganesyan Artem , Harutyunyan Lusine , Vanoyan Araksya , Martirosyan Nare , Badikyan Maria , Ghahramanyan Nerses , Oseyan Hasmik , Evoyan Levon , Farmazyan Armine , Chakhoyan Amalya , Grigoryan Hayk , Ter-Grigoryan Anahit , Sevoyan Anna , Gharibyan Avetis , Aynajyan Anahit , Hakobyan Karapet , Hakobyan Yervand 
Published: June 2023

TPS12149 Background: Oral mucositis (OM) is a serious complication of cancer treatments characterized by erythema and ulcerations of the mouth. Consequences of OM include pain, diminished functionality, and infections leading to decreased quality of life and discontinuity in therapy. About 20-40% of patients receiving chemotherapy develop OM within 7 days of treatment initiation. Current clinical guidelines recommend prophylactic oral care, cryotherapy, KGF-1, palifermin, and photobiomodulation to prevent OM in specific patient groups. Benzydamine is approved for the prevention of OM in head and neck cancer patients receiving radiotherapy or radio-chemotherapy but has not been well studied for chemotherapy alone. The effectiveness of oral topical treatments is limited by dilution in the saliva and swallowing shortening the duration of their action. Bocaliner is a novel medical device that is hypothesized to enhance the effects of treatments by prolonging the oral retention of topical therapies within the oral cavity. Methods: The Study for the Prevention of Oral Mucositis (SPOM) is a randomized controlled Phase I/II trial that aims to evaluate the efficacy of two different tools (benzydamine mouthwash and Bocaliner) in reducing the incidence and severity of OM in patients undergoing systemic chemotherapy (NCT05338398). A total of 100 adult patients with hematologic malignancies undergoing chemotherapy in a centralized hematology center in Armenia will be randomized into two different treatment groups: saline mouthwash and benzydamine mouthwash (0.15%, 120mL) 3-5 times a day for a total of two weeks. Half of the patients within each group will also randomly receive Bocaliner, which will be placed inside of their mouth immediately after the application of the mouthwash for 20 minutes. Block randomization will be applied with 4 patients per block with 1:1 randomization based on gender, Bocaliner use, and mouthwash type. The primary endpoint is the difference in OM incidence measured by the WHO Oral Toxicity Scale. The secondary endpoints are differences in OM symptoms evaluated using a modified version of the PROMS questionnaire. Safety and tolerability of the medical device will be determined for the Phase I component of the study based on responses to standardized tryout (Day 0) and follow-up questionnaires (Day 14). Other outcomes include the duration and severity of OM. Statistical analysis will explore further clinically meaningful associations between patient data, received therapies, and outcomes. Forty-two patients have already completed the study, while the enrollment of other participants continues and is planned to be completed by the end of 2023. Clinical trial information: NCT05338398 .
Exploratory study investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20).
Authors: Satomi Eriko , Ishikawa Ayaka , Arakawa Sayaka , Ishiki Hiroto , Amano Koji , Kobayashi Tomomi , Sakiyama Naomi , Otsuka Ryo , Maeda Makoto , Hashimoto Hironobu , Oyamada Shunsuke , Ariyoshi Keisuke , Kihara Kota , Mizushima Akio 
Published: June 2023

TPS12151 Background: In opioid therapy for cancer pain, it is essential to manage opioid-related adverse effects. Opioid-induced nausea and vomiting (OINV) is common, occurring in 20–40% of patients during initial opioid treatment or after opioid doses are increased. Tolerance to OINV develops within a few days to a week. In patients with cancer, OINV results in decreased quality of life as well as failure to relieve pain due to poor opioid adherence, thus increasing the psychological barriers to opioid use. Therefore, antiemetics are used for OINV prophylaxis, but their efficacy and safety in this context have not yet been fully elucidated. Olanzapine is a promising antiemetic for prophylaxis against nausea and vomiting induced by highly emetogenic chemotherapy, and it is less likely to cause extrapyramidal symptoms than haloperidol and prochlorperazine. We are conducting this exploratory study to evaluate the efficacy and safety of olanzapine prophylaxis against OINV. Methods: This single-arm, single-center exploratory study will evaluate the prophylactic antiemetic efficacy and safety of olanzapine (5 mg PO once a day for 5 days) in patients with cancer pain reserving initial regular opioid therapy. Thirty-five patients will be enrolled. This study was designed to provide preliminary efficacy data, with a primary objective of assessing the proportion of patients who achieved complete control (CC) of OINV during 120 hours of opioid treatment. CC was defined as the absence of emetic episodes, the lack of a need for rescue medication to treat nausea, and minimal or no nausea (3 or less on an 11-point categorical scale). Secondary endpoints include the following: the complete response (CR) rate, defined as the percentage of patients with no emetic episodes and no rescue medication use; the total control (TC) rate, defined as the percentage of patients with no emetic episodes, no rescue medication use, and no nausea during the 120 hours of opioid treatment; the time from opioid initiation to the first emetic episode; the time from opioid initiation to the first administration of a rescue antiemetic; the time to treatment failure, defined as the time from opioid initiation to the first emetic episode or to the administration of a rescue antiemetic; the number of emetic episodes; the levels of nausea, anorexia, sleepiness, pain, and fatigue, all determined using a numerical rating scale (0–10); the impact of antiemetic therapy on daily life severity and patient satisfaction, determined using a 7-grade categorical scale; and adverse events graded by PRO-CTCAE ver.1.0 and CTCAE ver. 5.0. The study is currently open, and 25 patients have been enrolled at time of abstract submission. Clinical trial information: jRCTs031220008 .
Progress report of a cross-organ and biomarker-based platform study: BELIEVE trial NCCH1901.
Authors: Ando Yayoi , Shimoi Tatsunori , Sunami Kuniko , Okita Natsuko Tsuda , Mori Mikio , Shibata Taro , Nakamura Kenichi , Yamamoto Noboru 
Published: June 2023

TPS1611 Background: Cancer Genomic Medicine (CGM) has been developing and more patients have received the comprehensive genomic profiling (GCP) test under national healthcare system in Japan. However, the number of patients who could receive the genomically matched therapy based on the results of CGP tests was limited. To improve the drug accessibility, we initiated a cross-organ, biomarker-based clinical trial (NCCH1901, the BELIEVE trial). It was a platform trial and could be considered as the Japanese counterpart to the National Cancer Institute's Molecular Analysis for Therapy Choice (NCI-MATCH) study in the United States. Methods: It was a multi-institutional joint research nationwide led by NCCH with a master’s protocol. Several drug cohorts were pre-established, allowing patients to participate in molecularly targeted treatments recommended as a result of CGP test. All drugs were provided for free from the pharmaceutical companies. The objective of this trial was to administer off-label drugs for the respective genomic abnormalities and collect efficacy and safety data for patients of the drugs. The primary endpoint was the response rate based on the best overall response for up to 16 weeks. This trial has been conducted under both of the Japanese Clinical Trial Act and the patient-proposed healthcare services which enable patients to receive unapproved, off-label drugs partially covered by National Health Insurance. The protocol and the informed consent forms were approved by the National Cancer Center Hospital (NCCH) certified review board and the Ministry of Health, Labour and Welfare (MHLW). The trial was registered in the Japan Registry of Clinical Trials (jRCTs031190104). As of January 31, 2023, we have 20 drug cohorts and the planned number of enrollments for each cohort was 50 with the target lesions and 30 without the target lesions. There were more than 500 patients so far. The most common cancer was brain tumours, followed by carcinoma of endocrine organs and the colorectal cancer. BRAF mutation and ERBB2 amplification were the frequent genomic abnormalities registered in this trial. Five drug cohorts have already finished recruiting and 2 drug cohorts assessed their efficacies. We are still continuing to discuss several pharmaceutical companies to increase the drugs cohorts in this platform. This trial is now recruiting the patients and is contributing significantly to increase the treatment opportunity for the cancer patients. Clinical trial information: jRCTs031190104 .
Phase 3 TRIDENT study (EF-32): Tumor treating fields (TTFields; 200 kHz) concomitant with chemoradiation, and maintenance TTFields therapy/temozolomide in newly diagnosed glioblastoma.
Authors: Shi Wenyin , Roberge David , Kleinberg Lawrence , Jeyapalan Suriya A. , Goldlust Samuel Aaron , Nagpal Seema , Lustgarten Leonardo , Combs Stephanie E , Nishikawa Ryo , Reardon David A. , Grossman Rachel , Glas Martin 
Published: June 2023

TPS2083 Background: Tumor Treating Fields (TTFields) therapy, a noninvasive and locoregional antimitotic cancer treatment modality, is approved for newly diagnosed (nd), recurrent glioblastoma (r) GBM and mesothelioma. In patients with ndGBM, progression-free survival (PFS) and overall survival (OS) were significantly improved with TTFields therapy/temozolomide (TMZ) vs TMZ alone in the pivotal EF-14 study, leading to FDA approval in ndGBM. To avoid potential impedance of radiotherapy (RT), TTFields therapy was administered following RT/TMZ; however, preclinical studies have demonstrated that TTFields therapy enhances the therapeutic effect of RT. Methods: TRIDENT (EF-32; NCT04471844), a phase 3, global, randomized study, will evaluate TTFields therapy concomitant with RT/TMZ in patients ≥18 years of age (≥22 years in the US) with histologically-confirmed ndGBM, ≥3 months life expectancy, and ≥70 Karnofsky performance status. Patients will be stratified on the basis of MGMT promoter methylation status and extent of resections. Approximately 950 patients will be assigned 1:1 to continuous TTFields therapy (200 KHz, ≥18 h/day) concomitant with RT/TMZ (experimental arm) or RT/TMZ alone (control arm). Patients in the experimental arm will receive TTFields therapy continuously from the first day of chemoradiation. Patients in the control group will begin TTFields at the same time as maintenance TMZ, approximately one month after completion of chemoradiation. TTFields therapy will continue in both treatment groups until second disease progression (PFS2) or 24 months (if clinically able). The primary endpoint is median OS, and secondary endpoints include PFS, 1- and 2-year survival rates, objective response rate, PFS2, 6- and 12-month PFS rates, safety, and quality of life (EORTC QoL questionnaires). The ability of TTFields therapy to extend OS in a dose-dependent manner is an exploratory endpoint. The sample size is powered for a hazard ratio of < 0.8 with a 5% type I error. The hypothesis that first-line TTFields therapy/RT/TMZ can significantly improve OS vs RT/TMZ will be tested using a stratified log-rank test. The study is expected to enroll patients at 150 sites, with enrollment currently open in 9 countries. Clinical trial information: NCT04471844 .
Efficacy and safety study of neoadjuvant efineptakin alfa (NT-I7) and pembrolizumab in recurrent glioblastoma.
Authors: Webb Mason , Burns Terry C , Twohy Erin , Sener Ugur , Kizilbash Sani Haider , Ruff Michael W. , Uhm Joon H. , Galanis Evanthia , D'Andre Stacy D. , Riviere-Cazaux Cecile , Lee Byung Ha , Flickinger Lynn M. , Parney Ian F. , Campian Jian Li 
Published: June 2023

TPS2085 Background: Glioblastoma (GBM) is the most common and aggressive form of brain tumor in adults. Despite maximal surgical resection, irradiation, and chemotherapy, median overall survival (OS) remains at only 30 weeks for recurrent GBM (rGBM) patients, emphasizing the need for novel treatments. GBM tumors are immunologically ‘cold,’ in that they have an immune-suppressive microenvironment with a low number of tumor-infiltrating lymphocytes (TIL). Interleukin 7 (IL-7) plays a key role in T cell development and survival. The physiological level of IL-7 increases to stimulate T cell expansion in lymphopenic condition. Previous studies have shown that lymphopenic GBM patients have shorter survival. However, their IL-7 levels are unexpectedly low. Efineptakin alfa (NT-I7), a long-acting IL-7, has been shown to increase effector CD8 T cells and reduce suppressor T-regulatory cells in murine GBM models, with subsequently improved OS. Further, we recently completed a Phase I study which showed that NT-I7 is safe, well- tolerated, and increased absolute lymphocyte counts (ALC) in newly diagnosed GBM patients. Phase II dosing was determined through this Phase I study reaching maximum tolerated dose. Thus, we hypothesized that NT-I7 may reverse GBM-associated immune suppression and potentiate the effect of an immune checkpoint inhibitor, leading to an increase in TILs and improved survival. Our preliminary data suggests that combining NT-I7 with pembrolizumab, an anti-PD-1 antibody, improves survival in murine glioma models. The purpose of this study is to evaluate the safety and efficacy of combining NT-I7 and pembrolizumab in rGBM patients. Methods: This is an open-label single arm one-stage Phase II study of NT-I7 and pembrolizumab as neoadjuvant and adjuvant therapy with surgery for adult patients with rGBM. We plan to enroll 30 evaluable patients, including a 6-patient safety run-in. Key eligibility criteria include candidates willing to undergo clinically indicated resection or biopsy, age ≥ 18 years, Karnofsky performance status ≥ 70, and dexamethasone dose > 2 mg/day ≤ 2 days prior to registration. The primary endpoint is a 9-month OS rate. Secondary endpoints include progression-free survival, objective response rate, changes in ALC, and adverse events profile. The correlative endpoints include studies to assess the anti-glioma immune response, changes in T cell subsets, T cell effector function, cytokine analysis, and immunohistochemical analysis of GBM tissue. Longitudinal cerebrospinal fluid proteomics is optional. This study opened on 1/20/2023. Two of the planned 30 patients had been enrolled by submission on 2/14/2023. Clinical trial information: NCT05465954 .
Phase 1 study of LB1410, a bivalent TIM-3/PD-1 bispecific antibody, in patients with advanced solid tumors or lymphoma.
Authors: Liu Jiajian 
Published: June 2023

TPS2663 Background: Cancer immunotherapies targeting PD-1 or PD-L1 have been proven effective in causing durable antitumor immune responses with less toxicity in many types of tumors. However, the response rate of anti-PD-1/PD-L1 treatments is far from satisfactory and most patients show primary or acquired resistance to the treatments. Tim-3, one of the next generation of immune checkpoint targets, co-expressed on exhausted T cells with PD-1. It is also expressed by innate immune populations, including NK and DC. Dual blocking PD-1 and Tim-3 not only on T cells but also on DC, NK cells may achieve better clinical benefit. LB1410 is a recombinant humanized anti-PD-1/TIM-3 bispecific antibody (BsAb) developed by L&L Biopharma Co., Ltd. for the patients who are resistant to or refractory from PD-1/PD-L1 treatments. It blocked the immune checkpoint PD-1 and TIM-3-mediated immunosuppressive signal pathways simultaneously, showed better T/DC cell activity and in vivo anti-tumor efficacy compared to Tim-3 and PD-1 antibody combination in preclinical studies. Methods: This is a FIH, multicenter, non-randomized, open label, phase 1 study of LB1410 in Participants With Advanced Solid Tumor or Lymphoma（Keyplus-001）. The planned sample size is approximately 100 patients in two parts: part 1 dose escalation will evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D), and Part 2 dose expansion will further characterize the safety profile and preliminary tumor response in several cohorts including NSCLC, CRC, EC etc. Enrollment criteria include adults with life expectancy of > 3 months, ECOG performance status 0-1，histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies or lymphoma for which standard treatment fails, or no standard treatment is available, or standard treatment is not applicable at this stage. Exclusion criteria include pregnancy, lactation, or breastfeeding, ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments. The primary endpoints are incidence of dose limiting toxicities and adverse events, MTD, and recommended phase 2 dose. Secondary objectives will evaluate PK parameters, preliminary antitumor activity, and immunogenicity of LB1410. Besides, the pharmacodynamics (PD) biomarkers related to LB1410 treatment, clinical activity will be explored. This clinical trial is in progress; cohorts 1 to 5 in dose escalation part have been completed. Clinical trial information: NCT05357651 .
A phase 1 first-in-human clinical trial of HMBD-002, an IgG4 monoclonal antibody targeting VISTA, in advanced solid tumors.
Authors: Rodon Ahnert Jordi , Gruber Joshua James , Telli Melinda L. , Mita Monica M. , Mita Alain C. , Kim Joseph W. , Villalona-Calero Miguel Angel , Patel Meera , Yadav Shalini S. , Sharma Padmanee , Haber Tom , Symons Jessica Lauren , Seet Qihui , Dharmadhikari Bhushan , Thakkar Dipti , Kwek Kon Yew , DiMascio Leah , Rowinsky Eric Keith , Ingram Piers , Boyd-Kirkup Jerome Douglas 
Published: June 2023

TPS2664 Background: V-domain Ig Suppressor of T-cell Activation (VISTA), is an immune checkpoint regulator found on tumor, myeloid, and other immune cells. Its presence has been shown to enhance tumor growth, create an immunosuppressive microenvironment, and may potentially contribute to developing resistance to anti-CTLA-4 and anti-PD-1/PD-L1 therapies. Therefore, VISTA represents a promising therapeutic target. HMBD-002, a non-depleting, high-affinity IgG4 monoclonal antibody against VISTA, has demonstrated significant inhibition of tumor growth in preclinical studies, both as a monotherapy and in combination with pembrolizumab. HMBD-002 acts by increasing T-cell activity and reprogramming the suppressive tumor microenvironment to a proinflammatory antitumor phenotype. Cancer types including triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC), which exhibit high expression levels of VISTA in the TME, provide a rational basis for exploring these indications in clinical studies. Methods: This phase 1/2, open-label, multi-center trial is being conducted in two parts to evaluate the safety, pharmacokinetics, and antitumor activity of HMBD-002, an IgG4 monoclonal antibody targeting VISTA, as a monotherapy and in combination with pembrolizumab. The dose-escalation stage (Part 1) will follow a standard 3 + 3 study design with weekly dosing and adaptive dose-escalation increments to determine the recommended phase 2 dose (RP2D) for subsequent disease-directed studies. Monotherapy escalation cohorts 1-4 have been completed without dose-limiting toxicities (DLTs). The dose-expansion stage (Part 2) will evaluate the antitumor activity of HMBD-002 alone and combined with pembrolizumab in patients with TNBC and NSCLC, as well as a wide range of VISTA-expressing malignancies. Exploratory analyses will be conducted to assess treatment-induced immunological changes both systemically and within the tumor microenvironment. Longitudinal blood samples will be evaluated using single-cell mass cytometry (CYTOF) and multiplex cytokine analysis. Pre and on-treatment tumor tissue samples will be assessed for VISTA & PD-L1 expression using IHC. Additionally, tumor tissues will be evaluated using multiplex immunofluorescence, and gene-expression profiling. Biomarker correlations with clinical outcomes may lead to the identification of predictive markers of response to HMBD-002. Clinical trial information: NCT05082610 .