bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autologous cytotoxic T-cell receptor T cell therapy (SCG101) against hepatitis B surface antigen phase I/II trial for patients with advanced hepatitis B-related hepatocellular carcinoma.
Authors: Abou-Alfa Ghassan K. , Yong Wei-Peng , Chang Stephen Lam , Fan Jia , Toh Han Chong , Yau Thomas , Choo SuPin , Wang Jing , Kusuma Nicole , Ma Christy , Qin Shukui 
Published: June 2023

TPS4181 Background: The overall prognosis of patients with advanced Hepatitis B-related hepatocellular carcinoma (HCC) remains poor, and treatment options are limited. In an IIT study conducted in China (NCT05339321), SCG101 following lymphodepletion (cy-flu) as second-line setting or beyond in patients with Hep B-related HCC has shown acceptable safety profile, reduction in HBsAg levels (>1 log) and tumor control. A phase I/II trial has been initiated to evaluate safety and RP2D of autologous SCG101 T cell therapy in Hepatitis B virus-related HCC (NCT05417932). Methods: This multicenter, open-label, 3+3 dose-escalation phase I trial is ongoing across 7 sites in the United States, Singapore and Hong Kong SAR, and a parallel study is done in mainland China across 8 sites. Eligible patients have a histologically confirmed HCC, not amenable to curative intent (surgery or locoregional therapy) and failed ≥2 standard line of therapies, match any of HLA-A*02:01, *02:02, *02:03, *02:04, *02:07, *02:09,*02:16, have positive serum (or tumor) HBsAg, HBV-DNA <2000 IU/ml, BCLC B or C, CP≤7, with measurable disease at screening (mRECIST and RECIST v1.1), ECOG PS<1. Patients with CNS metastasis, prior liver transplant, autoimmune disease or prior cell therapy are excluded. SCG101 T cells is manufactured in Singapore under cGMP and ship to all study sites across the U.S, Singapore and Hong Kong SAR, while SCG101 T cells for the China sites is manufactured in SCG Cell Therapy’s China facility. Patients will receive a single dose of SCG101 T cell therapy following lymphodepletion (cy-flu). Endpoints include safety, MTD and RP2D. Secondary endpoints include ORR, DOR, PFS, OS, changes in serum HBsAg. Safety is monitored together with Data Review Committee. The study is actively enrolling, and the phase II portion of the trial is expected to be initiated by H2 2023. Autologous SCG101 T cell therapy may provide a new treatment option for patients with advanced Hepatitis B virus-related HCC. Clinical trial information: NCT05417932 .
Alliance A021804: A prospective, multi-institutional phase II trial evaluating temozolomide versus temozolomide and olaparib for advanced pheochromocytoma and paraganglioma.
Authors: Del Rivero Jaydira , Perez Kimberly , Geyer Susan Michelle , Khalil Maged F. , Vijendran Aishwarya , Kordaris-Corkill Andrea , Shergill Ardaman , Spencer Kristen Renee , Soares Heloisa P. , Lopez Charles D. , Nixon Andrew B. , Dueck Amylou C. , Meyerhardt Jeffrey A. , O'Reilly Eileen Mary 
Published: June 2023

TPS4191 Background: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neuroendocrine tumors (NETs) that arise from chromaffin cells. Few antitumor therapies have been developed for patients (pts) with advanced PHEO/PGLs (APP). Potent poly (ADP-ribose) polymerase (PARP) is activated after DNA damage and regulates base excision repair, homologous recombination and non-homologous end joining. Inhibition of PARP enzymatic activity blocks PARP-mediated DNA repair, therefore PARP inhibitors can be directly cytotoxic to tumor cells which then permits synergy with agents that increase prevalence of single-strand breaks in tumor models. Temozolomide (TMZ) is an alkylating agent that induces single-strand DNA breaks and therefore is an optimal therapeutic pair with a PARP inhibitor. We are conducting a phase II multi-institutional study to evaluate the antitumor activity of TMZ and olaparib [OLA (a PARP inhibitor)] in patients with APP. Methods: Patients with APP with radiographic evidence of disease progression by RECIST v1.1 in the 12 months prior to registration can be enrolled in this phase II randomized study. Patients will be randomized in a 2:1 allocation with more patients to Arm 1. Arm 1 will receive TMZ 75 mg/m2 daily and OLA 200 mg twice daily on days 1-7 of a 21-day cycle. Arm 2 will receive TMZ 200 mg/m2 daily on days 1-5 of a 28-day cycle. Treatment on Arm 1 will continue for 13 cycles, followed by OLA maintenance until disease progression. Treatment on Arm 2 will continue for 13 cycles or until disease progression. The primary objective is to compare the progression-free survival between the two arms with a planned interim analysis for futility. Secondary endpoints include safety, response rate, and overall survival. Correlative endpoints include biochemical response and biomolecular markers (germline succinyl dehydrogenase mutations and tumor status of the repair enzyme methylguanine-DNA methyltransferase). We anticipate a null PFS median of approximately 5.4 months. We plan to accrue a total of 76 patients (randomized at a rate of 2:1 with more patients enrolled to the TMZ+OLA arm) in 38 months with a minimum follow-up of 2.5 months to achieve 56 PFS events. This design includes one interim analysis for futility using Rho Family spending functions (Rho = 2.5) and will yield 89% power to detect a hazard ratio (HR) of 0.5 (median PFS of 5.4 vs. 10.8 months) assuming exponential survival and using a one-sided log-rank test with type I error rate of 0.11. Clinical trial information: NCT04394858 .
LANTana trial protocol: An open label, single arm, phase Ib study to evaluate the effect of pre-treatment with ASTX727 (a demethylating agent) followed by lutetium Lu 177 dotatate in patients with progressive, metastatic neuroendocrine neoplasias (NENs).
Authors: Sharma Rohini , Ward Caroline , Naik Mitesh , Khan Saraih , Barwick Tara , Martinez Maria , Izadi Hooshang , Aboagye Eric O. 
Published: June 2023

TPS4192 Background: Neuroendocrine neoplasias (NENs) are characterised by the presence of somatostatin receptors (SSTR) on cell surface, in particular SSTR2. Somatostatin and its stable analogue (SSA) bind with high affinity to SSTR2. SSA can be radiolabelled, to both stage NENs using positron emission tomography (PET), and to deliver selective radiotherapy; peptide receptor radionuclide therapy (PRRT). PRRT consists of SSA linked to the long acting radionuclide. Radiolabelled SSA binds to SSTR2 and the complex is internalised delivering high dose radiation directly to the cancer. PRRT has been significantly improve survival outcomes and maintain quality of life in metastatic disease. Suitability for PRRT depends on presence of SSTR2 as determined by PET imaging, commonly with [68Ga]-dotatate-PET. 20% of patients will have low or no uptake on [68Ga]-dotatate-PET precluding PRRT. The upstream promoter region of SSRT2 is methylated, with percentage of methylation correlating with SSTR2 expression. We have shown that the use of the demethylating agent, guadecitabine, increases uptake on PET imaging in such that tumours previously negative on PET imaging, become positive, correlating with a dose dependent increase in tumoural SSTR2 expression. Combination guadecitabine and PRRT was well tolerated in vivo models of NETs. Overall aim was to utilise [68Ga]-dotatate-PET as a biomarker of SSTR2 re-expression following treatment with the demethylating agent, ASTX727, such that patients previously unsuitable for PRRT can receive therapy, improving clinical outcome. 1) Utilise [68Ga]-dotatate-PET to image epigenetic regulation of SSTR2 in response to ASTX727. 2) Evaluate clinical efficacy and safety of ASTX727 pre-treatment in combination with PRRT. 3) Explore impact on quality of life of combination therapy. Methods: 27 patients with no or equivocal uptake on [68Ga]-dotatate-PET will be enrolled. [68Ga]-dotatate-PET will be performed at baseline and after 8days of ASTX727 (oral, fixed dose 100mg cedazuridine + 35mg decitabine). If there is a significant increase in PET uptake, patients will receive combination ASTX727 and PRRT (Lutathera). Treatment will be repeated every 2months for 4 cycles. Response assessment (RECIST 1.1), tolerability and QoL will be assessed at start of each cycle. Tumour biopsies will be taken at baseline, and after cycle1 of ASTX727 (n=5), for SSTR2 methylation. Methylation will be correlated with PET uptake and outcome. LINE-1 methylation in peripheral blood monocytes will be assessed throughout. Current enrolment: 4. Clinical trial information: NCT05178693 .
Phase 1b/2 trial of pepinemab plus avelumab as second line combination immunotherapy for patients with metastatic pancreatic adenocarcinoma.
Authors: Ruffolo Luis I. , Fisher Terrence Lee , Evans Elizabeth E. , Mallow Crystal L. , Boise Megan , Foster Amber , Leonard John E. , Belt Brian A. , Yeh Jen Jen , Zauderer Maurice , Linehan David , Mulkerin Daniel 
Published: June 2023

TPS4195 Background: Monotherapy with immune checkpoint inhibitors (ICIs) is not effective in metastatic pancreatic adenocarcinoma (PDAC), likely due to the unique immunosuppressive tumor microenvironment (TME) of PDAC, thus safe and novel strategies to overcome resistance and facilitate adaptive immune responses are a major unmet need. Preclinical and clinical studies demonstrated that antibody blockade of semaphorin 4D (SEMA4D) promotes tumoral infiltration and activation of DCs and CD8+ T cells and reverses immunosuppression, including attenuation of MDSC recruitment and function, leading to enhanced efficacy of ICIs without increasing toxicity. Pepinemab, a SEMA4D blocking antibody, in combination (combo) with avelumab provided clinical benefit in some patients with ICI-resistant and PD-L1-low NSCLC (NCT03268057). Pepinemab is also being evaluated in combo with pembrolizumab in patients with metastatic squamous cell carcinoma of the head and neck (NCT04815720). The principal goals of this proof-of-concept study are to investigate the safety, efficacy, and TME biomarker changes of treatment with the combo of pepinemab plus avelumab in patients with metastatic PDAC. Methods: This single-arm, open-label study (NCT05102721) is evaluating the safety, tolerability, and efficacy of pepinemab in combo with avelumab in patients diagnosed with metastatic PDAC who have either progressed on or are otherwise intolerant to first line chemotherapy. Patients must have received 5FU or gemcitabine-based first line therapy with evidence of intolerance or treatment failure, including progression both during or after completing first-line treatment. Accrual for the Phase 1b portion follows a Bayesian Optimal Interval Design (BOIN), beginning at the highest dose combo; 20 mg/kg pepinemab and 800 mg avelumab Q2W. Phase 2 begins after 16 subjects are enrolled at MTD, permitting a Simon’s two stage assessment of futility prior to closing the Phase 1b period. The primary objective for Phase 1b is tolerability, and the primary objective for Phase 2 is therapeutic efficacy compared to historical second-line systemic chemotherapy. The trial anticipates a total evaluable cohort of 40 subjects and is powered to detect a response rate of 23% or greater, with alpha set at 0.1 and 80% power. Exploratory objectives include robust correlative analysis of immune, stromal, and genomic profiling of baseline and on-treatment tumor biopsies to ascertain mechanisms of treatment response and failure. Patient reported outcomes are incorporated throughout the trial to assess disease specific symptoms associated with pancreatic cancer and cancer cachexia. One patient has been enrolled as of Feb 14, 2023. Clinical trial information: NCT05102721 .
A phase 1 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of LB4330, a peptide fused to CLDN18.2 antibody targeting the tumor antigen associated CD8+t CELLS in patients with advanced solid tumors.
Authors: Liu Jiajian ,   L&L Team
Published: June 2023

TPS4196 Background: PD-1/PD-L1-targeted immunotherapies have become critical roles in the treatment for many tumors. However, there is limited progress in pancreatic ductal adenocarcinoma (PDAC). PDAC is low immunogenicity. PDAC microenvironment is immunosuppressive. More than 70% PDACs have few or no CD8+ T cells around the tumor cell or in the tumor microenvironment (TME). Therefore, immunotherapy like PD-1/PD-L1 antibody alone is rarely effective for PDACs. Some cytokine or analogs may activate CD8+ T cells. An analog specifically activating tumor antigen associated (TAA) CD8+ T cells was designed and fused to anti-CLDN18.2 antibody. This specific bi-functional molecule LB4330 has high affinity to human anti-CLDN18.2 (14pM) and CD8+T cells. LB4330, as a novel, first-in-class molecule, may activate TAA CD8+ T cells in TME and has potential in alone or in combination with PD-1/PD-L1 mAb, for the treatment of advanced solid tumors, especially for Claudin 18.2 positive PDAC. Methods: This is a FIH, phase 1 study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of LB4330 in patients with advanced solid tumors (MEETCD8-001). The planned sample size is approximately 66 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). Part 2 dose expansion will further characterize the safety profile and preliminary tumor response in advanced gastric and gastroesophageal junction adenocarcinoma and PDAC with Claudin 18.2 expression. In dose escalation stage, patients will be recruited with advanced solid tumors who have failed standard treatment, or for whom standard treatment is not available or applicable at this stage. Exclusion criteria include a greater risk for gastric bleeding, irritable bowel syndrome with symptoms, active virus infections. 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 LB4330. Tumor response will be assessed per RECIST and iRECIST every 2 cycles. The Phase I study in advanced solid tumors is ongoing. Enrollment in cohort 1 began in Nov 2022. Clinical trial information: NCT05707676 .
A phase III randomized trial of eribulin (E) with or without gemcitabine vs standard of care (SOC) for metastatic urothelial carcinoma (UC) refractory to or ineligible for PD/PDL1 antibody (Ab): SWOG S1937.
Authors: Sadeghi Sarmad , Plets Melissa , Lara Primo N , Tangen Catherine , Bangs Rick , Lerner Seth P. , Flaig Thomas W. , Petrylak Daniel P. , Thompson Ian M 
Published: June 2023

TPS4608 Background: UC is 2nd most common genitourinary cancer. Current SOC offers platinum-based (PB) first line chemotherapy (chemo) with ddMVAC or gemcitabine-cisplatin (GC) regimens. For cisplatin ineligible patients (pts), SOC includes gemcitabine-carboplatin (GCa), and in select pts pembrolizumab. Erdafitinib is approved for pts with FGFR alterations and Enfortumab vedotin (EV) is approved for previously treated pts. A phase I/II CTEP study of eribulin (E) for metastatic UC (mUC) established the activity of E in UC with objective response rate (ORR) of 37.5% and a median progression free survival (PFS) of 4.1 months (mo) and median overall survival (OS) of 9.5 mo (N=150). A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed an ORR of 50%, median OS of 11.9 mo and median PFS of 5.3 mo (N=24). The most common Grade 3-4 toxicities included: neutropenia 63%, anemia and fatigue 29%. Pts with liver metastases benefited from therapy with 5 responders in 7 pts for GE vs 12 out 49 E. Methods: This is a phase III, randomized 3 arm study comparing E vs. GE vs. SOC (docetaxel, paclitaxel, or gemcitabine). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle. In the GE arm, gemcitabine is added to E at 1000 mg/m2 dose to D1 and D8. SOC follows standard dosing of the agents. There is no limit to the number/sequence of prior regimens. A simplified summary of eligibility criteria is presented here. All pts must have: received frontline systemic treatment such as PB chemo or a non-platinum regimen; received PD1/PDL1 Ab or be deemed ineligible for PD1/PDL1 Ab; received EV. Assuming a median OS for the SOC arm of 7 mo the study seeks to find at least a 50% increase in median OS to 10.5 mo (Hazard Ratio (HR) = 0.667). One-sided 0.0125 type I error to account for testing of two primary hypotheses (Each arm vs. SOC). 87% power to detect a 3.5 mo improvement in OS. We require 140 eligible (155 total) pts in each arm for a total of 465. The study was activated in Feb 2021 and accrual is ongoing. Clinical trial information: NCT04579224 .
A phase II trial with copanlisib plus avelumab as maintenance therapy for metastatic bladder cancer after platinum-based chemotherapy.
Authors: Farrukh Hizra , Zhu Zheng , Zhu Shaoming , Montgomery Robert Bruce , Meeks Joshua J , VanderWeele David James , Wong Yu-Ning , Lew Robert A , Pan Chong-xian 
Published: June 2023

TPS4610 Background: Bladder cancer is the tenth most common malignancy and the fourteenth most common cause of cancer death worldwide. Currently, platinum-based chemotherapy followed by avelumab maintenance immunotherapy is the first-line standard of care for advanced bladder cancer (aBC). Even though maintenance avelumab therapy has improved overall survival, its efficacy is still disappointing with a response rate of less than 10% and progression-free survival benefit of 1.7 months. The phosphoinositide 3-kinase (PI3K) pathway harbors more activating alterations than any other growth signaling pathway in aBC. Furthermore, PI3K δ and γ are expressed by immune cells and regulate their function. Activation alterations along the PI3K pathway are putative molecular drivers and can possibly be targeted for the treatment of aBC. In preclinical studies, we found that a pan-PI3K class I inhibitor, copanlisib, potentiates anti-programmed cell death 1 (PD1) antibody in syngeneic bladder cancer mouse models with or without activation alterations along the PI3K pathway (Zhu S, J Immunother Cancer. 2021). We hypothesize that copanlisib potentiates avelumab as maintenance therapy for aBC. Methods: This is a multi-center, single-arm, open-label Phase II trial with a lead-in safety phase to determine the efficacy and toxicity of combination copanlisib and avelumab maintenance therapy in aBC. The major inclusion criteria are patients with aBC without disease progression after platinum-based chemotherapy and no contraindication for avelumab and copanlisib. With a type I error of 5% and power of 80% with a log-rank test, we will need 26 patients for this study. With an attrition rate of 10%, we will enroll 29 patients from four US Department of Veterans Affairs Medical Centers. Copanlisib will be administered through intravenous infusion (IV) at 60 mg on Day 1, 8 and 15, and avelumab will be administered 800 mg IV on Day 1 and 15 of each 4-week treatment cycle for up to 26 cycles. Imaging will be repeated every two cycles during first year of therapy and thereafter every 3 cycles or clinically indicated. The primary endpoint is progression-free survival (PFS). The secondary endpoints include CT or MRI determined radiographic overall response rate, toxicity, overall survival, and molecular correlative studies. Kaplan-Meier estimates will be presented together with median PFS with 2-sided 95% confidence intervals (CI). In particular, the PFS rates at 3, 6, 9, 12 and 15 months will be estimated with corresponding 2-sided 95% CIs. Adverse events will be assessed according to CTCAE v5. Tumor response is determined according to Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1 criteria. This study is currently open for enrollment. Clinical trial information: NCT05687721 .
Phase 2 trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder.
Authors: DeCastro Guarionex Joel , Anderson Christopher B. , Abate-Shen Cory , Gray Jillian , Ingram Justin , Stein Mark N. , McKiernan James M. 
Published: June 2023

TPS4616 Background: For patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacille Calmette-Guerin (BCG), multi-agent intravesical trials have been limited. The goal of this Phase 2 study is to investigate the efficacy of intravesical chemotherapy consisting of sequential cabazitaxel, gemcitabine, and cisplatin (CGC) in the salvage setting. Phase 1 results reporting on 18 subjects demonstrated adverse events limited to local Grade 1 and 2 toxicities. Partial funding support for the trial was provided by a pharmaceutical company. Methods: This is a Phase 2 trial (NCT02202772) presently enrolling patients with BCG unresponsive NMIBC as defined by the FDA who refuse or are ineligible for radical cystectomy. All patients undergo pre-treatment transurethral resection of bladder tumor (TURBT) and a 6-week regimen of intravesical cisplatin (100mg), gemcitabine (2gm), and cabazitaxel (5mg). Each drug is instilled weekly except for cisplatin, which is given every other week. Complete response is defined as having no evidence of cancer on post-induction biopsy and negative urine cytology at 3 months. Complete responders proceed with monthly and bimonthly maintenance therapy without cisplatin in the first and second years, respectively, for a total of 24 months. Results: To date thirty-one patients have been enrolled (with target accrual of 33), of whom seven are female. One patient withdrew consent before first evaluation cystoscopy. Mean age thus far is 72 years. All patients have previously received at least two prior induction cycles of BCG, and meet FDA criteria for BCG unresponsive disease. All patients have biopsy proven high grade disease at enrollment; 8 (27%) have high grade T1 disease; and 20 (67%) patients have CIS. Conclusions: Salvage options for BCG unresponsive NMIBC are limited. The CGC protocol has been demonstrated to be safe in a previous Phase 1 study, and accrual for this Phase 2 is near completion. Clinical trial information: NCT02202772 .