bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of nivolumab and ipilimumab in children and young adults with INI1-negative cancers.
Authors: Forrest Suzanne J. , Yi Joanna , Kline Cassie , Cash Thomas , Reddy Alyssa Terry , Cote Gregory Michael , Merriam Priscilla , Czaplinski Jeffrey , Bhushan Ketki , DuBois Steven G. , Janeway Katherine A. , Kao Pei-Chi , London Wendy B. , Chi Susan N. , Collins Natalie Bucheimer 
Published: June 2021

TPS10055 Background: Several aggressive pediatric and young adult cancers are characterized by SMARCB1 inactivation resulting in loss of INI1 expression, including rhabdoid tumors, epithelioid sarcoma and undifferentiated chordoma. These malignancies are associated with a poor prognosis and few effective treatment options for relapsed or refractory disease. Prior studies and emerging data suggest INI1-negative cancers may be uniquely susceptible to treatment with immune checkpoint inhibitors: Many INI1-negative pediatric tumors express PD-L1 and are infiltrated by immune cells, and there are reports of patients with advanced INI1-negative cancers with clinical responses to immune checkpoint blockade (Forrest et al. Clinical Cancer Research, 2020). We hypothesize that INI1 loss predicts tumor response to immune checkpoint inhibition (ICI). Methods: This is an ongoing multicenter, phase II, open-label clinical trial to evaluate the activity of nivolumab and ipilimumab in patients aged 6 months to 30 years with relapsed or refractory INI1-negative cancers (NCT04416568). The study enrolls patients in 2 strata: extracranial solid tumors in Stratum 1 and intracranial solid tumors in Stratum 2. Patients treated with prior ICI are excluded. Patients are treated with intravenous (IV) nivolumab 3mg/kg plus ipilimumab 1mg/kg IV every 3 weeks for 4 cycles followed by nivolumab 3mg/kg (max dose 240mg) IV every 2 weeks for up to 1-year. The primary objective is to evaluate the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) for Stratum 1 and by Response Assessment in Neuro-Oncology (RANO) criteria for Stratum 2. The trial has a 2-stage design targeting a 25% or greater response rate, with each stratum assessed independently. The analysis for Stage 1 in a given Stratum will be performed after 10 patients are enrolled. If a sufficient number of responders are observed, an additional 10 patients will be enrolled at Stage 2. Secondary endpoints include progression-free survival, overall survival, and disease control rate at 12 months. Correlative aims include assessing tissue and blood biomarkers associated with treatment response. Enrollment began 14 Aug 2020 and is ongoing. Clinical trial information: NCT04416568.
Comprehensive ambulatory monitoring during immunotherapy in patients with advanced melanoma: A prospective trial (CAMP-IT).
Authors: Kos Milan , Buffart Laurien , de Groot Jan Willem , Westgeest Hans , Dercksen Wouter , Van Laarhoven Hanneke W.M. , van Oijen Martijn G.H. 
Published: June 2021

TPS1589 Background: The emergence of immune checkpoint inhibitors has improved survival outcomes for patients with advanced melanoma. However, these treatment modalities are also associated with specific immune-related toxicities. These are often reversible after prompt recognition and initiation of appropriate management, but can result in severe morbidity and hamper health-related quality of life (HRQoL) if left undetected. Hence, accurate and regular monitoring of these patients is critical. Recent advances in mHealth technologies and the rapidly expanding armamentarium of wearable devices allow for real-time objective (vital signs and physical activity) data and patient-reported outcome measurement (PROMs) collection and, hence, serve this purpose. We hypothesize that collection of real-time objective data adds to the early detection of disease- and treatment-related adverse events. The primary objective of this study is to determine the feasibility of collecting real-time PROMs, vital signs, and physical activity data in advanced melanoma patients receiving immunotherapy using a comprehensive ambulatory monitoring platform (CAMP) that consists of a smartphone app, activity monitor, digital thermometer, and online dashboard for physicians. Methods: In this prospective multi-center trial, patients (n = 50) with advanced melanoma, scheduled to receive immunotherapy with immune checkpoint inhibitors, and with access to a smartphone are eligible for inclusion. Consenting patients will be asked to wear a FitBit Versa 2.0 during waking hours, collect daily temperature measurements using a Withings Smart Temporal thermometer, and answer weekly toxicity questionnaires (NCI PRO-CTCAE) using the smartphone app for the duration of the study (12 weeks). Primary outcome is feasibility in terms of (i) participation rates, (ii) wear-time, (iii) compliance rates with in-app questionnaires and temperature measurements, and (iv) satisfaction with the platform. Secondary exploratory outcomes include associations between CAMP-derived parameters and clinical outcomes: performance status (PS), HR-QoL scores (EORTC QLQ-C30 questionnaire), unplanned hospitalizations, physician-assessed adverse events, and 1-year survival outcomes. PS and HR-QoL will be rated at baseline, mid-study, and end-of-study. The occurrence of adverse events will be documented up to 12 months from baseline. Survival outcomes will be compared to a propensity score matched group from the Netherlands Cancer Registry. Accrual has started in February 2021. Clinical trial information: NL8827.
First-in-human dose escalation and food effect study of oral ONC206 in adults with recurrent primary CNS neoplasms.
Authors: Theeler Brett James , Jung Jinkyu , Burton Eric , Leeper Heather , Wu Jing , Zaghloul Kareem , Ray-Chaudhury Abhik , Quezado Martha , Raffeld Mark , Yuan Ying , Aldape Kenneth D. , Penas-Prado Marta , Prabhu Varun Vijay , Stogniew Martin , Allen Joshua E. , Armstrong Terri S. , Gilbert Mark R. 
Published: June 2021

TPS2072 Background: The majority of recurrent CNS tumors lack effective systemic therapy options following surgical resection and adjuvant radiotherapy. ONC201, the founding member of the imipridone class of small molecules, has induced durable tumor regressions in patients with diffuse midline glioma, H3 K27M-mutant (DMG H3K27M). ONC206, the second imipridone to enter clinical development, is a DRD2 antagonist and ClpP agonist that exhibits differentiated receptor pharmacology and gene expression profiles in tumors relative to ONC201. The compound is orally bioavailable, penetrates the blood-brain barrier, and exhibits anti-cancer efficacy without toxicity in several preclinical cancer models with pronounced efficacy in myc-overexpressing CNS tumors. Methods: A first-in-human, open label, dose escalation, and food effect Phase I study of oral ONC206 (NCT04541082) is currently enrolling. Patients must be 18 years or older and diagnosed with a recurrent, primary CNS neoplasm. Eligible diseases include recurrent glioblastoma, WHO Grade 2 and 3 infiltrating glial neoplasms, DMG H3K27M, ependymoma, medulloblastoma, malignant meningiomas, and other rare primary CNS neoplasms. Dose escalation, initially with weekly dosing, will follow a standard 3+3 design. After the MTD is established, a food effect cohort will enroll with a balanced, single-dose, two-arm, two-period, crossover design. The primary endpoint is to determine DLT during the first 28-day cycle. Secondary endpoints will include objective response rate by RANO criteria, overall and progression-free survival, and disease control rate. Exploratory biomarker analyses based on preclinical correlations with efficacy will include DRD2, DRD2 dimer, ClpP, DRD5, c-myc, and n-myc expression. Clinical trial information: NCT04541082.
Phase I study investigating the safety of stereotactic body radiotherapy (SBRT) with anti-PD-1 and anti-IL-8 for the treatment of multiple metastases in advanced solid tumors.
Authors: Karapetyan Lilit , Olson Adam C. , Gooding William E. , Bao Riyue , Chmura Steven J. , Luke Jason J. 
Published: June 2021

TPS2681 Background: Anti-PD-(L)1 immunotherapy improves outcomes for patients across various cancers; however, many patients do not benefit. Previous studies combining multi-site SBRT with anti-PD1 have confirmed feasibility and revealed induction of interferon signaling by SBRT. Elevated levels of serum IL8 (sIL8) associate with lack of response to anti-PD1 and we have observed that elevated IL8 is strongly associated with lack of response to immunotherapy and SBRT combinations. Overcoming IL8 induced epithelial-mesenchymal transitioning and trafficking of myeloid derived suppressor cells in tumor microenvironment therefore represents a promising strategy to overcome resistance. BMS-986253 is a fully human neutralizing antibody that binds to sIL8. The combination of BMS-986253 and nivolumab was safe in patients with advanced solid tumors. The present study aims to evaluate safety and preliminary efficacy of combining BMS-986253 with nivolumab and SBRT in patients with advanced solid tumors, Melanoma (MEL) and Renal Cell Carcinoma (RCC). Methods: This is a phase 1 open label single arm study (CT.gov: NCT04572451) which will include safety and efficacy cohorts. Patients will receive SBRT in 1-4 tumor lesions, in 3 or 5 fractions, at the total of 30 or 45 or 50 Gy based on the irradiated organ site. This will be followed by intravenous (IV) nivolumab (480mg q4 weeks (W)) and IV BMS-986253 (2400mg q2W) within seven days of completing SBRT. In the initial safety portion of the clinical trial, we will include 30 patients with advanced/metastatic solid tumors in order to evaluate safety. The primary endpoint of dose limiting toxicity will be assessed by continual Bayesian monitoring. The toxicities will be attributed to combination of SBRT/Immunotherapy as opposed to individual components. The secondary objective of the study is efficacy with an endpoint of objective response rate (ORR) as assessed by RECIST v1.1 in Mel and RCC. We will include 20 patients with MEL and RCC and compare against a historical benchmark of 20% ORR as sufficient signal of activity for further study. ORR will be assessed for association with serum IL-8 levels and radiation-induced changes in peripheral blood T cell populations. Clinical trial information: NCT04572451.
Phase 1b dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of GS-3583, a FLT3 agonist Fc fusion protein, in patients with advanced solid tumors.
Authors: Brody Joshua , Thompson John A. , Tolcher Anthony W. , Kuhne Michelle R. , Huang Xi (Rochelle) , Kwan Ellen , Petrarca Michael , Dauki Anees , Singh Indrajeet , Rajakumaraswamy Nishanthan , Kummar Shivaani 
Published: June 2021

TPS3147 Background: Productive antitumor immune responses in nonclinical models depend on a type of dendritic cell (DC), conventional DC subtype 1 (cDC1), which in the context of cancer, primes tumor-reactive T cells through presentation of tumor-derived antigens. FMS-related tyrosine kinase 3 ligand (FLT3L) is a hematopoietic growth factor that binds to and activates FLT3 on terminally differentiated DCs. Activated FLT3 promotes proliferation, inhibits cell death, and is required for the differentiation, expansion, and maintenance of DCs in peripheral and lymphoid organs. GS-3583 is a fusion protein composed of the extracellular domain of recombinant human FLT3L fused to an engineered fragment crystallizable (Fc) region of human immunoglobulin G4. GS-3583 has PK properties that support sustained cDC in patients and potential combination with established immunotherapies. This phase 1b, open-label, multicenter, dose-finding study will evaluate safety, tolerability, PK, and preliminary efficacy of GS-3583 monotherapy in patients with advanced solid tumors (NCT04747470). Methods: Approximately 33 adults aged ≥18 years with a histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available will be enrolled. The study employs a 3+3 dose escalation design in which GS-3583 is administered intravenously for up to 52 weeks or until progressive disease or unacceptable toxicity. Up to five dose escalation cohorts have been planned. The maximum tolerated dose is the highest dose with incidence of DLT in < 33% of 6 or more patients in the first 28 days of GS-3583 dosing; recommended phase 2 dose will be determined. Assessments include safety, PK, pharmacodynamics including cDCs, immunogenicity, and efficacy by RECIST 1.1 in CT/MRI imaging conducted every 8 weeks. Accrual at approximately 3-4 centers in the US is ongoing. Clinical trial information: NCT04747470.
A phase II study of short course FOLFOX chemotherapy with either nivolumab (Nivo) or Nivo plus radiation in the first line treatment of metastatic or unresectable gastroesophageal (GEA) cancers.
Authors: Mehta Rutika , Mukherjee Sarbajit , Klute Kelsey , Park Haeseong , Khan Uqba , Khan Sahrish , Puello Carina , Machado Sabrina , Christos Paul J. , Sanfilippo Nicholas J. , Shah Manish A. 
Published: June 2021

TPS4157 Background: GEA remains incurable and novel therapies are needed. Studies have shown that cytotoxic chemotherapy can enhance antigenicity of tumors, leading to the recent practice changing studies that demonstrate checkpoint inhibition therapy combined with chemotherapy in PD-L1 overexpressing patients significantly improves patient survival (Keynote-590 and Checkmate-649). But long-term use can also subsequently dampen the immune response. Moreover, the stop-and-go strategy with chemotherapy can maintain patient survival while minimizing chemotherapy related side effects when compared to the traditional strategy of continuous chemotherapy. These observations prompted the inception of this trial with the hypothesis that a short course of FOFLOX therapy combined with immunotherapy will likely have similar activity to that of continuing FOFLOX until disease progression when combined with immunotherapy. We also will examine the hypothesis that low dose radiotherapy can further augment immunotherapy efficacy. Methods: This is a multicenter, randomized phase II study examining Nivo alone vs radiation therapy (RT) with Nivo in subjects who did not have disease progression with 3 months of FOLFOX + Nivo. Subjects with advanced unresectable or metastatic GEA cancer are eligible. All subjects will receive FOLFOX + Nivo therapy. Subjects who demonstrate at least stable disease, on their first imaging assessment at 2 months will receive 1 additional month of FOLFOX + Nivo, and then will be randomly assigned at a 1:1 ratio to receive either Nivo alone or Nivo + RT. After 4 mos of therapy, patients who remain on study will receive Nivo Q4WKly. The primary endpoint is to demonstrate that the addition of fractionated radiation to immunotherapy is associated with an improvement in the 12-month progression-free survival (PFS) proportion from 25% (i.e., historical control estimate; Nivo alone; Arm A) to approximately 50% (i.e., with the fractional radiation and Nivo; Arm B). A key secondary aim is to demonstrate that short course FOLFOX of 3 months + Nivo is similar in efficacy to continuing FOLFOX until disease progression. Another secondary aim of this study is to demonstrate safety of the combination of fractionated RT + Nivo. Target sample size is 74 patients. The study is now open at six sites across the United States. Clinical trial information: NCT04021108.
CaboRISE: A phase II study evaluating reduced starting dose and dose escalation of cabozantinib as second-line therapy for advanced HCC in patients with compensated liver cirrhosis.
Authors: Trojan Jorg , Pluntke Stefan , van Boemmel Florian , Ehmer Ursula , Goetze Thorsten Oliver , Jacobasch Lutz , Pink Daniel , Kopp Christina , Lehnerts Sarah , Riedel Johanna , Waidmann Oliver , Finkelmeier Fabian , Geißler Michael 
Published: June 2021

TPS4163 Background: The multi-targeted tyrosine kinase inhibitor cabozantinib is approved for the treatment of advanced hepatocellular carcinoma (HCC) in adults, who have previously been treated with sorafenib. In the pivotal phase 3 CELESTIAL trial a significant improvement for OS and PFS was shown for cabozantinib in comparison to placebo treated patients (Abou-Alfa GK et al. N Engl J Med 2018; 379:54-63). However, in 62% of patients a dose reduction of cabozantinib was necessary and the median average daily dose was 35.8 mg. The discontinuation rate due to treatment-related adverse events (TRAEs) was 16% and grade 3-4 TRAEs occurred in 68% of patients. For HCC patients treated with sorafenib in first-line, a reduced starting dose of 200 mg BID was not inferior in terms of OS but showed a trend toward a decreased rate of sorafenib discontinuation(Reiss KA et al. J Clin Oncol 2017; 35:3575-3581). The aim of the CaboRISE trial is to study the effect of a reduced starting dose of cabozantinib on tolerability, safety, and efficacy. Methods: The CaboRISE trial is an open-label, single arm, multicenter phase II trial, including patients with advanced stage hepatocellular carcinoma (HCC) with compensated liver cirrhosis (Child-Pugh A) in second line treatment, after first line treatment with sorafenib or lenvatinib. Forty evaluable patients will be enrolled in the study to receive a reduced starting dose of 40 mg cabozantinib once-daily for 4 weeks and subsequent dose escalation to 60 mg cabozantinib once-daily to be maintained until disease progression or intolerable toxicities. The objective of the trial is to assess the tolerability of a reduced starting dose of cabozantinib, in order to reduce the treatment discontinuation rates due to treatment-related adverse events below 10%. Primary endpoint is the treatment discontinuation rate due to TRAEs. Secondary endpoints are overall survival, progression free survival at 10 weeks, objective response rate, time on treatment, treatment exposure, toxicity, and quality of life. Study start of the CaboRISE trial was in October 2020. By February 2021, 7 centers across Germany have been initiated and a total of 4 out of 40 planned patients have been enrolled. The study is currently ongoing. This study is financially supported by Ipsen. ClinicalTrials.gov: NCT04522908 EudraCT: 2020-000775-20. Clinical trial information: NCT04522908.
Trial in progress: Open-label, randomized, comparative phase 2/3 study of combination immunotherapy plus standard-of-care chemotherapy and SBRT versus standard-of-care chemotherapy for the treatment of locally advanced or metastatic pancreatic cancer.
Authors: Seery Tara Elisabeth , Nangia Chaitali Singh , Sender Leonard S. , Reddy Sandeep K. , Soon-Shiong Patrick 
Published: June 2021

TPS4174 Background: Pancreatic cancer will claim an estimated 47,050 lives in the USA in 2020, with an expected 5 year survival of 10%. Thus there is an urgent need for novel treatment options in this disease. We hypothesize that effective response against pancreatic cancer requires a coordinated approach that orchestrates both the innate and adaptive immune system. We further hypothesize that by orchestrating the activation of the entire immune system, we could accomplish immunogenic cell death with durable responses in this disease. We describe a novel combination immunotherapy protocol of low-dose chemoradiation, cytokine-induced NK and T cell activation via N-803 (an IL-15 cytokine fusion protein), and off-the-shelf PDL1-targeted high-affinity NK cell (PDL1 t-haNK) infusion. Methods: The ongoing QUILT 88 phase II/III, multi-center, three-cohort, open-label, US study (NCT04390399) to evaluate the comparative efficacy and overall safety of standard-of-care chemotherapy versus standard-of-care chemotherapy in combination with aldoxorubicin HCl, N-803, and PD-L1 t-haNK in subjects with locally advanced or metastatic pancreatic cancer. Each treatment setting (ie, first line maintenance, second line, or third line or greater) will be evaluated independently as a separate cohort. Subjects with locally advanced or metastatic pancreatic cancer who have received at least 16 weeks of treatment with gemcitabine plus nab-paclitaxel, and have had either a partial response (PR), CR, or stable disease (SD), will be enrolled into Cohort A to receive first-line maintenance therapy. Subjects who have disease progression on or after receiving first-line treatment with gemcitabine plus nab-paclitaxel or another first-line chemotherapy regimen (eg, FOLFIRINOX), or who have discontinued first-line treatment (eg, due to toxicity or intolerance) will be enrolled into Cohort B to receive second-line therapy randomized to irinotecan-liposome/5FU/LV versus experimental arm. Subjects who have disease progression after receiving at least 2 lines of therapy for pancreatic cancer, will be enrolled into Cohort C to receive third-line or greater treatment. Primary endpoints by cohort are: A) PFS per RECIST V1., B & C) OS. The secondary endpoints include overall response rate, DoR, DCR, OS(cohort A) and QoL by patient-reported outcomes. Clinical trial information: NCT04390399.
ENGOT-ov54/Swiss-GO-2/MATAO including LOGOS (Low-Grade Ovarian cancer Sub-study): MAintenance Therapy with Aromatase inhibitor in epithelial Ovarian cancer—A randomized, double-blinded, placebo-controlled, multicenter phase III Trial.
Authors: Heinzelmann-Schwarz Viola A. , Kurzeder Christian , Schmid Seraina , Gabriel Natalie , Mueller Andreas , Fehr Mathias Konrad , Marth Christian , Du Bois Andreas , Klar Maximillian 
Published: June 2021

TPS5598 Background: The prognosis of advanced epithelial ovarian cancer (OC) is poor with a relapse rate of 75% at 5 years. Some 80% of OC express estrogen receptor (ER). This is the first trial that wants to capitalize on this and prospectively evaluates letrozole, a potent aromatase inhibitor, as initial maintenance treatment for high and low grade OC. Methods: Eligible pts have primary OC, FIGO Stage II-IV with low or high grade serous or endometrioid histology, with (interval) debulking surgery, ECOG-status 0-2, Positivity (≥ 1%) for ER expression, and at least 4 cycles of platinum-based chemotherapy (neoadjuvant allowed). Pts are allowed to undergo concurrent maintenance treatment with bevacizumab and PARP inhibitors. Extensive quality of life (QoL) questionnaires via an App and physical activity measurements by a tracking device as well as G8 geriatric score, ESGO surgery questionnaire, and Charleson Comorbidity Index are routinely assessed. Primary objective is to evaluate the efficacy of letrozole maintenance therapy after standard surgical and chemotherapy treatment as measured by Progression Free Survival (PFS) compared to no maintenance therapy (placebo). Primary outcome is PFS, defined as time from date of first letrozole/placebo administration until date of progression or death by any cause. Stratification for high and low grade histologies and ER measurement is performed via a digital centralized pathology review process. Final analysis will be performed for the whole cohort and for the subgroup of low grade ovarian cancers (LOGOS subprotocol). Secondary objectives and outcomes are overall survival (OS), quality adjusted progression free survival (QAPFS), time to first subsequent treatment (TFST), quality adjusted time without symptoms (TWiST), and health related QoL. Study is designed as international, randomized (1:1 ratio), two-arm, multi-centric, double-blinded, placebo-controlled superiority phase III trial. In total, 528 pts will be randomly assigned to letrozole or placebo for 5 yrs or until unacceptable toxicity, progression of underlying disease, or study discontinuation. Final analysis is planned after 5 years without interval analysis and follow-up is collected for up to 10yr and for the low-grade cohort for up to 12yr. Clinical trial information: NCT04111978.