bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 2 trial of the CDK4 inhibitor dalpiciclib in well-differentiated or dedifferentiated liposarcoma.
Authors: Liu Zengjun , Liu Mengyao , Xu Jing , Hu Wenyu , Zhang Hui , Tao Rongjie , Li Xinyu , Cha Lichao , Cui Jinfang , Zhao Junkai , Fu Heng , Fan Chunxiang , Tian Lantian , Qiu Fabo , Zhu Dongyuan 
Published: August 2024

11547 Background: The oncogene cyclin-dependent kinase 4 (CDK4) is amplified in > 90% of well-differentiated liposarcomas (WDLS) and dedifferentiated liposarcomas (DDLS). Previous studies have already demonstrated the clinical benefit of CDK4 inhibitors in the treatment of WDLS and DDLS. Dalpiciclib is a more potent and novel CDK4 inhibitor. We designed a multi-center phase 2 study to evaluate the safety and efficacy of dalpiciclib in patients with advanced WDLS/DDLS. Methods: Eligible patients were adults aged 18 years and older, with a confirmed diagnosis of advanced WDLS/DDLS, measurable lesions according to RECIST 1.1, any (or no) priory therapy, and a history of progression by RECIST 1.1 in the 6 months prior to enrollment. All patients were required to have CDK4 amplification by fluorescence in situ hybridization and retinoblastoma (RB) protein expression by immunohistochemistry. All patients were treated with dalpiciclib 150 mg orally once per day for 21 consecutive days within a 28-day treatment cycle. The primary endpoint was progression free survival (PFS) at 12 weeks. Secondary end points included objective response rate and adverse events. Results: From August 2022 to October 2023, a total of 32 patients were enrolled, and 30 were evaluable for the primary end point. Median (range) age was 59 (40-76) years; 22 patients (69%) were male. At 12 weeks, PFS was 61.3% (95% CI, 44-78.5%). The median PFS was 17.4 weeks (95% CI, 10.65-24.15 weeks). Only one patient had a partial response to the treatment. Grade 3 to 4 events included neutropenia (37.5%), anemia (6.25%), thrombocytopenia (6.25%), and nausea (3.13%). Conclusions: Treatment with the CDK4 inhibitor dalpiciclib was associated with a favorable PFS rate in patients with advanced CDK4-amplified and RB-expressing WDLS/DDLS. Clinical trial information: ChiCTR2200062868.
Safety and efficacy of eribulin plus anlotinib in patients with advanced soft tissue sarcoma (ERAS): A multi-center phase II study.
Authors: Liu Jie , Deng Yaotiao , Wang Ying , Zhang Jie , Li Mei , Jiang Yu 
Published: August 2024

11561 Background: Both the microtubule-dynamics inhibitor eribulin and the multi-targeted tyrosine kinase inhibitor anlotinib exhibit single-agent anti-tumor activity in previously treated soft tissue sarcoma (STS). This study aimed to evaluate the efficacy and safety of the combination treatment of eribulin and anlotinib in patients with advanced STS. Methods: In this multi-center phase II study (ERAS), patients with advanced soft tissue sarcoma who relapsed/progressed after anthracycline chemotherapy or were not candidates for such treatment were included. Patients received eribulin (1.1 mg/m² intravenously on days 1 and 8) and anlotinib (12mg orally once daily on days 1-14) every 21 days for 6-8 cycles, followed by anlotinib maintenance. The primary endpoint was progression-free survival rate at 24 weeks (PFR24w). Secondary endpoints included median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), disease control rate (DCR) and safety. Results: Thirty-one patients were enrolled. Twenty-eight (90.3%) patients had received anthracycline chemotherapy, and the remaining 3 (9.7%) were chemotherapy-naïve. Pathological types included L-type sarcomas (10 leiomyosarcomas and 6 dedifferentiated liposarcomas) and non-L-type sarcomas (n =15, with 8 subtypes). As of the cut-off date of Jan 28, 2024, the median follow-up time was 30.4 weeks. Response evaluation was feasible in 29 patients. The ORR, DCR and predicted PFR24w were 20.7%, 82.8% and 65.5%, respectively. The mPFS was 30.1 weeks, with no significant difference observed between patients with L-type sarcomas and non-L-type sarcomas. The mOS was not reached. Nineteen (61.3%) patients experienced at least one grade 3/4 adverse event. The most common grade 3/4 adverse events included neutropenia (35.5%), leukopenia (25.8%), hypertension (16.1%), hypertriglyceridemia (16.1%) and increased gamma-glutamyl transpeptidase (16.1%). Conclusions: The combination of eribulin and anlotinib shows promising efficacy with an acceptable toxicity profile in patients with advanced STS, irrespective of pathological type. Clinical trial information: ChiCTR2300067650.
Improving chemotherapy-induced alopecia for women receiving anthracycline plus taxane chemotherapy using the Paxman scalp cooling system at lower temperatures.
Authors: Goldfarb Shari Beth , Jamner Alanna , Toumbacaris Nicolas , Gordon Allison , Chen Yuan , Abdo Nadia , Dacunto Analisa , Blinder Victoria Susana , Fornier Monica N. , Chang Cassandra , Lacouture Mario E. 
Published: August 2024

12143 Background: Chemotherapy-induced alopecia (CIA) not only impacts physical appearance but may also be detrimental to patient’s psychological well-being. To address CIA, patients often use scalp cooling devices such as the FDA-approved Paxman Scalp Cooling System (PSCS), currently approved at -5°C. This study explores the potential benefits of lower temperatures, -7.5°C and -10°C, to improve the efficacy of PSCS in minimizing CIA. Methods: This prospective study analyzed data from 33 women with stage I-III breast cancer receiving anthracycline and taxane chemo at MSKCC from 12/2019–10/2022. Photography, trichoscopy, and toxicity checks were conducted at baseline, weeks 4, 8 (primary endpoint), end of treatment (EOT), and 24 weeks post-chemotherapy. 23 patients reached week 8, while 10 withdrew prior due to lack of efficacy (5/10), change in treatment (3/10), or anxiety (2/10). Successful hair preservation (HP) was defined as CTCAE v4 grade 0 or 1 alopecia. Results: At baseline, all patients had grade 0 alopecia. At week 4, 81% achieved successful HP (17/21), and at week 8, over half maintained it (53%; 9/17). The majority had HP at EOT (69%; 11/16). At 24 weeks post-chemotherapy, all patients demonstrated continued HP (100%; 11/11) and all evaluated patients at 18 months post-treatment had grade 0 alopecia (100%,4/4). Among women with baseline photographs and trichoscopy (n=25), median average hair count at baseline was 154.0 per cm² and width 70.2 per cm². By week 4 (n=21), the median average hair count decreased by 20.0%, and width decreased by 8.0% compared to baseline. By week 8 (n=17), average count improved by 15% compared to week 4 (-3% from baseline) and average width decreased by 6% (-7.5% baseline). At EOT hair count decreased 37.8% and width decreased by 11.6% compared to baseline (n=16). At 24 weeks post-EOT there was a 13% increase in median average hair count with no measurable change in width compared to baseline (n=12). No patients (0%; 0/33) reported dose-limiting toxicities (DLTs) at -7.5°C (n=7) or -10°C (n=26). Conclusions: Patients successfully tolerated scalp cooling at lower temperatures, with no reported dose-limiting toxicities and successful HP. This study indicates higher HP rate at EOT (69%; 11/16) compared to studies using PSCS at -5°C. Post-EOT data shows successful hair regrowth with a higher average hair count than pre-treatment. A larger sample size is needed to assess the additional benefit of lower temperatures on HP and regrowth. Clinical trial information: NCT.[Table: see text]
Evaluation of survival outcomes in patients with solid organ cancer with brain metastasis treated with exacta encylopedic tumor analysis based treatments.
Authors: Kurzrock Razelle , Limaye Sewanti , Massoudi Farzad , Datar Rajan , Srinivasan Ajay , Gosavi Rahul Ashok , Datta Vineet , Syed Nelofer , Crook Tim 
Published: August 2024

2033 Background: Brain metastasis in solid organ cancers presents a challenging scenario with an adverse prognosis and limited systemic treatment options. Treatment of such patients becomes more challenging because most drugs can't cross the blood-brain barrier, besides the treatment being too harsh for sensitive brain parenchyma. Moreover, these patients are frequently excluded from clinical trials, reflecting concerns about their poor prognosis influencing trial outcomes and potentially distorting efficacy data. While almost all cancers metastasize to the brain, cancers of the breast, lungs, kidney and melanoma carry a higher risk. Methods: The Resilient Study, a Phase-II, single-arm, open-label interventional trial, focused on evaluating the efficacy of Exacta Encyclopedic Tumor Analysis (ETA)-guided treatment for a range of solid organ cancers in patients who had failed multiple lines of treatment and were broadly refractory. 143 patients were recruited out of whom 126 patients were evaluable. Prior to treatment initiation, all patients underwent PET-CT and MRI scans to assess the extent of the disease. 9 out of 126 patients (7.1%) were found to have metastatic deposits of the brain comprising 6/21 patients (29%) of breast cancer, 2/5 patients (40%) of lung cancer, and 1/15 patient (7%) of colorectal cancer. Utilizing freshly biopsied tumor tissue (primary/lymph node/liver) and peripheral blood, Exacta ETA was performed, encompassing gene mutations, gene expression, and in vitro chemosensitivity profiling of viable tumor cells. Exacta ETA-derived personalized therapy recommendations were administered to patients. Follow-up data for OS was collated. Results: Median overall survival (OS) was not reached at the time of analysis. By considering the OS values censored at the interim (most recent follow-up), the median OS was 9.7 months (95% CI 7.06 - 12.3 months; range: 1 month – not reached) among patients without brain metastases (n = 117, 92.8%) and 10 months (95% CI 2.6 - 15.9 months; range: 2.6 months – not reached) among patients with brain metastases. Conclusions: Our data shows that personalized Exacta ETA-guided treatments resulted in almost similar OS for patients with brain metastases as seen in patients or without brain metastases. These findings stand out as significant considering the poor outcomes with Standard of Care treatments in patients with brain metastases. Clinical trial information: CTRI/2018/02/011808.
Initial data from a phase 1, first-in-human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumors.
Authors: Thomas Sajeve Samuel , Pico Brian , Henick Brian S. , Leidner Rom , Samhouri Yazan , Isaacs James , Weiss Jared , Hurwitz Michael E. , Grewal Jaspreet Singh , Luke Jason J. , Chattopadhyay Shrikanta , Wang Yun , Motta Marlyane , Murray Jim , Barton Debora , Pinchasik Dawn , MacBeath Gavin , Moser Justin C 
Published: August 2024

2542 Background: Solid tumors are notoriously heterogenous with highly variable antigen expression and an immunosuppressive microenvironment. HLA loss of heterozygosity (LOH) has also been identified in up to 40% of solid tumors, allowing tumor cells to evade T cell attack. To overcome these issues and a lack of potent endogenous antitumor T cells in cancer patients, TScan has developed T-Plex, a multiplexed cell therapy comprising two to three different TCR-Ts, chosen from a collection of TCR-Ts called the ImmunoBank. Product and study design details were presented at ASCO 2023 (Abstract #2554). Methods: A screening protocol (NCT05812027) pre-identifies patients with solid tumors any time during clinical care, enabling rapid enrollment into the treatment protocol (NCT05973487) upon disease progression. TCR-Ts currently in the master protocol target PRAME on HLA-A*02:01; HPV16 on HLA-A*02:01; MAGE-A1 on HLA-A*02:01, HLA-A*01:01, or HLA-C*07:02; or MAGE-C2 on HLA-B*07:02. All TCR-Ts in the ImmunoBank and master protocol are first tested as single therapies in dose levels 1 and 2 before becoming available for multiplexing in dose levels 3 and 4. Results: From September 2023 to the time of abstract submission, 140 participants with a variety of solid tumors were enrolled in the screening protocol and are in different stages of screening. To date, 65% have ≥1 HLA match, and 20% and 6% have 2 and 3 HLA matches, respectively, highlighting the advantage of including TCR-Ts targeting multiple different HLA types within the same master protocol. Of those who have completed target screening, 92% express at least one target and 65% qualify for at least one TCR-T. Intratumoral heterogeneity of target expression was observed even with the most prevalently expressed target, PRAME, supporting the rationale for multiplexed TCR-T treatment. Although HLA-LOH affects only half of HLA genes and the remaining intact HLA alleles in tumors can still be recognized by TCR-Ts, about 13% of participants had LOH of the targeted HLA allele, excluding them from TCR-T treatment. Conclusions: Initial data indicate that the combination of HLAs and targets in the ImmunoBank results in ≥1 TCR-T match for the majority of solid tumor patients evaluated to date, and many patients qualify for multiplexed TCR-T treatment. LOH testing can prevent selection and treatment with a TCR-T that would not confer benefit. The proportion of patients eligible for multiplexing is expected to increase as the ImmunoBank grows. Updated data on screened and treated patients will be presented at the meeting. Clinical trial information: NCT05973487 ; NCT05812027 .
Phase 1 trial of TU2218, TGFβ-RI and VEGF-R2 dual inhibitor in monotherapy and combination with pembrolizumab in patients with advanced solid tumors.
Authors: Oh Do-Youn , Tolcher Anthony W. , Chaudhry Arvind , Lee Arielle Shebay , Chaney Marya F. , Kim Kyu-Pyo , Kim Hun-taek 
Published: August 2024

2613 Background: Pembrolizumab interrupts PD-1/-L1 interaction and is efficacious in many cancers. However, resistance may emerge in some of the patients treated. VEGF and TGF-β pathways play an important role in the development and function of the tumor-microenvironment (TME), contributing to be the immunosuppressive. TU2218 is a highly potent, orally available dual inhibitor against TGFβ type I receptor (ALK5) and VEGFR2. This was a first-in-human study to investigate the safety and tolerability of TU2218 monotherapy and combination therapy with pembrolizumab. Methods: This non-randomized, open-label, multinational, multicenter study evaluated the safety, tolerability, PK, and preliminary efficacy of TU2218 alone and combination with pembrolizumab to determine the Recommended Phase 2 Dose of the Combination (RP2DC) in advanced solid tumors. Eligible patients were ≥ 18 years of age, ECOG performance status of 0 or 1 and had measurable lesion per RECIST 1.1. Part A of monotherapy was sequentially escalated to 6 dose levels of TU2218 ranging from 30 to 270 mg/day on a 2 weeks-on/1 week-off regimen using a BOIN design. In part B, patients received TU2218 doses of 105, 150 and 195 mg/day on a 2 weeks-on/1 week-off cycle in combination with pembrolizumab 200mg once every 3 weeks. Dose escalation followed a 3+3 design with a DLT evaluation period. Results: In the TU2218 monotherapy dosed BID (n=22), no Grade 3 or higher treatment related AE was reported, while all Grade 2 TRAEs were tolerable. Systemic exposure to TU2218 increased in a dose dependent manner. Following seven days of administration, TU2218 demonstrated reductions in PD markers and a correlation was observed between TU2218 exposure and the decrease of PD markers, particularly TGF-β1 (-16.5%) and CTGF (-45.4%) blood levels in groups of TU2218 Cmax ≥ 1.0 μM. Patients (n=12) received TU2218 at doses levels of 105 to 195mg/day in combination with pembrolizumab 200mg once every 3 weeks. The most frequently observed TRAE was pruritus (25%, n=3) and one patient experienced Grade 3 TRAE with maculo-papular rash (8.3%, n=1). No DLT was observed during the dose escalation and the MTD was not identified. The best ORR in the combination cohort demonstrated PR at 8.3% (n=1), SD 50% (n=6) and PD at 33% (n=4). The dose level at 195mg/day of TU2218 in combination with pembrolizumab was safe and tolerable. Conclusions: TU2218, a first-in-class oral dual inhibitor against TGFβRI and VEGFR2 was well-tolerated in the monotherapy and in the combination therapy with pembrolizumab. The RP2DC was established for subsequent trials in specific cancer types. Clinical trial information: Phase 1a: NCT05204862 / Phase 1b: NCT05784688 .
Stereotactic body radiotherapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) versus TACE and TKIs alone for unresectable hepatocellular carcinoma (uHCC) with portal vein tumor thrombus (PVTT): A randomized controlled trial.
Authors: Duan Jiayu , Zhou Jitao , Liu Chang , Jiang Hanyu , Zhou Jin , Xie Kunlin , Wu Hong , Zeng Yong , Wang Xin 
Published: August 2024

4102 Background: TKIs-based systemic therapy is a primary treatment option for uHCC. Clinical studies have established the effectiveness and safety of radiotherapy (RT) in patients with PVTT, who typically have a poor prognosis. Previous research has shown that combining TACE and RT can extend survival in HCC patients with PVTT compared to sorafenib treatment. This study aimed to explore the efficacy and safety of combined local therapy (TACE plus SBRT) and TKIs in HCC patients with PVTT. Methods: This single-center, randomized controlled study enrolled patients aged ≥18 years with HCC and PVTT. Additional eligible criteria included ECOG PS 0-1, Child-Pugh score ≤B7, no extrahepatic metastasis on CT scan, and normal liver volume ≥700cc. Patients were randomly assigned to either the SBRT+TACE+TKIs group (Group A) or the TACE+TKIs group (Group B). SBRT was administered at 35-45 Gy in 5 fractions, 3 fractions per week. TKIs (sorafenib 0.4g bid; donafenib 0.2g bid; or lenvatinib 8mg/12mg qd, depending on body weight) were paused during the perioperative period of TACE (up to 4 times). The primary endpoint was the 6-month progression-free survival (PFS) rate, with secondary endpoints including objective response rate (ORR), overall survival (OS), disease control rate (DCR) and treatment-related adverse events (TRAEs). Treatment response was evaluated using mRECIST. Results: A total of 90 patients with uHCC were enrolled from June 2019 to October 2023 in this trial, with baseline characteristics presented in the Table. As of January 5th 2024, the median follow-up time was 14.5 months [IQR, 2.43-55]. The 6-month PFS rate was significantly higher in Group A (78%) compared to Group B (36%, P=0.0245). Group A also showed prolonged median PFS (9.75 vs. 4.89 months, HR=1.703 [95%CI, 1.045-2.777], P=0.0245) and OS (17.93 vs. 9.61 months, HR=1.869 [95%CI, 1.059-3.266], P=0.017). Improved ORR was observed in the SBRT group (74.4% vs. 40.5%, P=0.0015). DCR was 81.4% in Group A and 66.7% in Group B ( P=0.1211). The most common grade 3/4 TRAEs were hypertension (Group A: 17.8%, Group B: 13.3%, P=0.5608), ALT elevation (Group A: 26.7%, Group B: 22.2%, P=0.6237), and AST elevation (Group A: 22.2%, Group B: 15.6%, P=0.4191). There was one treatment-related death in Group B due to liver failure. Conclusions: In uHCC patients with PVTT, the combination of SBRT and TACE-TKIs showed significant survival benefit without the identification of any severe safety concerns. Clinical trial information: ChiCTR1900025300. [Table: see text]
Improving patient understanding of GEP test results (IMPARTER4): An RCT.
Authors: Fallowfield Lesley , Solis-Trapala Ivonne , Starkings Rachel , Matthews Lucy , May Shirley , Jenkins Valerie A 
Published: August 2024

527 Background: We developed two 8 min films to aid patients’ understanding about gene expression profiling (GEP) tests (Oncotype DX or Prosigna) in breast cancer. A previous study of 120 women without breast cancer demonstrated significantly better knowledge after film viewing compared to that after reading written materials (1). We present results of an RCT testing the films’ utility when given in clinics to women with early HR+ breast cancer for whom the benefit of chemotherapy was uncertain. Methods: Standard information policies about GEP testing differ, some clinics may provide patients with leaflets, others only verbal information. Patients who had consented to a GEP test were invited to join IMPARTER4. At baseline they completed anxiety trait/state and intolerance of uncertainty (IoU) questionnaires and were then randomized to Gp A (hospitals’ standard information alone) or Gp B (standard information plus the relevant GEP patient film). Prior to learning their risk of recurrence scores, researchers interviewed patients and probed their understanding and knowledge about GEP testing together with the role risk scores had in helping determine management options (hormone therapy plus or minus chemotherapy). Following test result discussions with oncologists, patients completed two further questionnaires measuring anxiety and decisional conflict. Treating physicians all completed IoU questionnaires once at baseline, Satisfaction with their clinical interviews conducted with patients about risk scores and management decisions was measured using a study specific questionnaire. Results: To date 225/230 patients from 18 UK hospitals (Gp A (standard information alone) n=103; Gp B (standard plus information film) n=122) were seen by 79 physicians. Socio-demographics, anxiety trait/state and IoU did not differ between groups. Prior to the results discussion, written information was given to 128/225 (56.9%), (66 in Gp A, and 62 in Gp B). Linear regression analyses (adjusted for age and education) showed that mean knowledge scores were higher in those receiving standard information plus the film (Gp B), (2.5 points (95% C.I:1.7-3.4) p<0.001). There was a trend for longer consultations in those patients having standard information alone (Gp A) (12.6% v 8.2%), who also asked more difficult questions (9.7% v 2.5%). Conclusions: Patient information films significantly improved knowledge about GEP tests and recurrence risk results compared to standard verbal and written information alone. Furthermore, the films appeared to enable shorter, more informed discussions between patients and their oncologists about the addition of chemotherapy to hormone therapy alone. Versions in Spanish, Italian, French, Urdu, Hindi, Gujarati, Punjabi, and Bengali are freely available. 1. Fallowfield et al, Br Ca Res & Tmt. 2022. Clinical trial information: 28497350.