tbuckley/cabot-search huggingface dataset:
Updated results from a phase II study of penpulimab plus anlotinib as first-line therapy in metastatic urothelial cancer (mUC).
Authors: Bo Yang, Qi Xiong, Qi Song, Yaping Long, Gang Guo, Hongzhao Li
Journal: Journal of Clinical Oncology (2024)

4573 Background: Cisplatin-based chemotherapy is the standard-of-care systemic treatment for mUC patients with good physical status and organ function, which has shown a response in more than 40% of patients, with mOS approximately 15 months. With the advent of immune checkpoint inhibitors, there are more explorations and options for first-line treatment of locally advanced or mUC. However, here is an ongoing unmet need for improved first-line treatment. Immune checkpoint inhibitors combined with anti-angiogenic therapy have a synergistic effect. Studies have reported that penpulimab combined with anlotinib have good efficacy and safety in multiple solid tumors. This study aimed to evaluate the efficacy and safety of penpulimab plus anlotinib as first-line therapy for mUC (ChiCTR2200056732). Methods: In the single-arm, phase Ⅱ study, eligible patients were aged 18-75 years with mUC who had no prior systemic therapy and ineligible or rejected for cisplatin-based therapy or any platinum-based chemotherapy, measurable lesion (according to RECIST v1.1), and ECOG PS of 0-2. Patients received penpulimab 200 mg intravenously on day 1 and anlotinib 8 mg orally once daily on day 1 to 14 every 3 weeks until progression, intolerable toxicities, or completion of 24 months of treatment. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: From Feb. 2020 to Dec. 2023, 29 patients of mUC were successfully enrolled and received at least once time treatment. Among them, 79.3% (23/29) were males and 20.7% (6/29) were females, with a median age of 64 years (range, 49-74). 10 of 29 (34.48%) patients had a history of smoking. 24.1% (7/29), 72.4% (21/29) and 3.45% (1/29) patients were ECOG PS 0, 1 and 2, respectively. PD-L1 expression was detected in 25 patients, of whom 52.0% (13/25) had TPS &lt; 1, 36.0% (9/25) had TPS≥1%, &lt;50%, and 12.0% (3/25) had TPS≥50%. At data cutoff (January. 1. 2024), a total of 24 patients were evaluated with a median follow-up time of 8.3m (95% CI, 2.8-13.8). The ORR was 62.5% (95% CI, 40.6-81.2) and DCR was 95.8% (95% CI, 78.9-99.9). The median PFS was 12.1 months (95% CI, 3.5-20.7). The median OS was not reached and 12-month OS rate was 100%. Frequent treatment-related adverse events of all grades included creatinine increased (16.7%) and transaminase elevation (10.0%). Grade 4 toxicity of liver dysfunction occurred in two patient (6.9%). No treatment-related death was observed. Conclusions: Penpulimab plus anlotinib demonstrated promising antitumor activity and manageable safety profile with no new safety signal in mUC. Clinical trial information: ChiCTR2200056732.
Efficacy and safety of fruquintinib in patients with metastatic colorectal cancer according to prior treatment sequence in the refractory setting: Results from FRESCO and FRESCO-2.
Authors: Tanios S. Bekaii-Saab, Arvind Dasari, Cathy Eng, Sara Lonardi, Takayuki Yoshino, Alberto F. Sobrero, James C. Yao, Pilar Garcia-Alfonso, Andrea Sartore-Bianchi, Howard S. Hochster, Joleen M. Hubbard, Timothy Jay Price, David Tougeron, Shukui Qin, Jin Li, William R. Schelman, Songhua Fan, Ziji Yu, Lucy F. Chen, Josep Tabernero
Journal: Journal of Clinical Oncology (2024)

3579 Background: Fruquintinib (F) is a highly selective, oral tyrosine kinase inhibitor of all 3 VEGF receptors. Based on FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) data, F was approved by the US FDA for previously treatedmetastatic colorectal cancer (mCRC). Efficacy and safety of F + best supportive care (BSC) vs placebo (P) + BSC were analyzed according to prior treatment (tx) sequence using FRESCO and FRESCO-2 data. Methods: In FRESCO and FRESCO-2, patients (pts) were randomized 2:1 to receive F 5 mg or matching P, PO daily x 21 days every 28 days. In FRESCO, eligible pts had received ≥2 prior chemotherapy regimens and were permitted to have received prior anti-VEGF and/or anti-EGFR therapies, whereas in FRESCO-2, in addition to standard chemotherapies, anti-VEGF, and anti-EGFR therapies if indicated, prior exposure to trifluridine/tipiracil (TAS) and/or regorafenib (rego) was required. FRESCO-2 pts must have also received a BRAF inhibitor and/or immunotherapy, if indicated and available in their country. Results: In FRESCO (F n=278 vs P n=138), no pts had received rego and 16/416 pts (4%) had received TAS. InFRESCO-2, prior therapies were balanced between F vs P arms; pts had received prior TAS or rego in these sequences: prior TAS only (n=240 vs n=121); prior rego only (n=40 vs n=18); prior rego then TAS (n=84 vs n=45); prior TAS then rego (n=95 vs n=44). Improvements in OS and PFS were seen with F vs P regardless of prior tx sequence (Table), with similar magnitudes of benefit for OS (HRs 0.53–0.77) and PFS (HRs 0.25–0.37). F safety profile was consistent regardless of prior tx sequence (Table). Conclusions: F is effective in mCRC with a manageable safety profile regardless of prior TAS or rego tx and sequence. Improvement with F was similar for OS and PFS despite the number and sequence of prior regimens. F provides a new tx option for pts with previously treated mCRC regardless of prior TAS or rego exposure. Clinical trial information: NCT04322539 . [Table: see text]
Camrelizumab plus apatinib for advanced renal cell carcinoma patients after first-line tyrosine kinase inhibitor treatment failure: A multicenter phase II trial.
Authors: Lijuan Jiang, Xia Zheng, Wensu Wei, Yulu Peng, Deling Wang, Zhiling Zhang, Shengjie Guo, Hui Han, Xiuyu Cai, Fangjian Zhou, Pei Dong
Journal: Journal of Clinical Oncology (2024)

4539 Background: Previous studies have demonstrated the benefit of combining immunotherapy with antiangiogenic agents in patients with advanced renal cell carcinoma (aRCC). The efficacy of apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (TKI), has been documented in aRCC. In contrast, the efficacy of camrelizumab, a PD-1 inhibitor, has not been reported in RCC, although its efficacy and safety have been established in various cancer types. This study aims to evaluate the efficacy and safety of camrelizumab plus apatinib in aRCC following the failure of first-line TKI therapy. Methods: This multicenter, single-arm, phase II trial enrolled patients with aRCC who had failed first-line TKI treatment. Patients received 200 mg of camrelizumab intravenously every two weeks and 250 mg of apatinib orally once daily until disease progression or unacceptable toxicity occurred, with camrelizumab treatment lasting up to two years. The primary endpoint was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Between August 2020 and January 2024, 35 patients were enrolled in the study and received treatment. The median age was 57 years (range: 39-81), with 31 (88.6%) being male. A total of 27 (77.1%) patients presented with lung metastases. As of the cut-off date, January 8, 2024, the median follow-up duration was 16.5 months (range: 0-33). Of these patients, 12 (34.3%) achieved a partial response, and 17 (48.6%) maintained stable disease, resulting in an objective response rate of 34.3% (95% confidence interval [CI], 19.1-52.2) and a disease control rate of 82.9% (95% CI, 66.4-93.4). Two out of five patients with progressive disease (PD) benefited from continued treatment with camrelizumab plus apatinib for more than 4 months after the first PD. The median PFS was 10.0 months (95% CI, 6.1-14.9), and the median overall survival was 28.4 months (95% CI, 19.7-not reached). Of all patients, 27 (77.1%) experienced treatment-related adverse events of grade 3 or higher, with the most common being proteinuria (25.7%), hypertension (20.0%), and alanine aminotransferase increased (14.3%) and aspartate aminotransferase increased (14.3%). Conclusions: The combination of camrelizumab and apatinib demonstrates encouraging antitumor activity and a favorable safety profile as a second-line treatment option for patients with aRCC. Clinical trial information: ChiCTR2000034384. [Table: see text]
Phase I trial of CRD3874-SI, a systemically administered STING agonist, in patients with advanced solid tumors.
Authors: Ciara Marie Kelly, Viswatej Avutu, Lauren Baker Banks, Jason Earl Chan, Ping Chi, Camron Clark, Olivia Counihan, Mark Andrew Dickson, Mrinal M. Gounder, Mary Louise Keohan, Robert G. Maki, Sujana Movva, Damon R. Reed, Evan Rosenbaum, Anna Szostek, Li-Xuan Qin, Phillip Wong, William D. Tap, Sandra P. D'Angelo
Journal: Journal of Clinical Oncology (2024)

TPS2690 Background: Identifying novel approaches that harness and augment anti-tumor immune responses represents an important area of ongoing research and drug development. Stimulator of interferon genes (STING) is an endoplasmic protein receptor that acts as an innate immune mediator by generating protective type 1 interferons when cytosolic DNA is detected in cells. STING also channels protons across golgi membranes promoting autophagy and pyroptosis. CRD3874-SI is a first in class small molecule allosteric STING agonist and potent activator of all five human STING variants that promotes the release of inflammatory cytokines from downstream interferon genes. It has demonstrated promising pre-clinical anti-cancer activity in several tumor mouse models. CRD3874-SI demonstrated high levels of systemic safety in cynomolgus monkeys, thought to be related to its ability to inhibit STING proton channel activity. Methods: This is a single institution, phase 1a/b study of CRD3874-SI in patients with advanced sarcoma and Merkel cell carcinoma who have received at least one line of prior therapy. The dose escalation phase will explore the safety and tolerability of CRD3874-SI across 6 dose levels following a standard 3+3 design. Dose expansion in subtype specific sarcoma and Merkel cell carcinoma is planned on completion of the dose escalation phase of the study. CRD3874-SI will be administered by intravenous infusion once per week for 2 cycles. From cycle 3 onwards, participants will receive three consecutive weekly infusions followed by one week break, over a 28-day treatment cycle. The primary objective is to assess the safety and tolerability of CRD3874-SI by determining the maximum tolerated dose, recommended phase 2 dose and schedule of administration. Secondary objectives include further defining the safety profile, examining the pharmacokinetics and pharmacodynamics (CXCL10 analysis) of CRD3874-SI and evaluating the efficacy of CRD3874-SI as determined by best objective response rate and clinical benefit rate per RECIST v 1.1. Treatment will continue for up 6 cycles or until disease progression or unacceptable toxicity. Cross sectional imaging will be used to measure clinical activity. Adverse events will be evaluated using NCI-CTCAE v5.0 criteria. This study is currently open to enrollment and dosing has commenced. Clinical trial information: NCT06021626 .
Preliminary results from a phase II clinical study of first-line drugs combined with stereotactic body radiotherapy (SBRT) in the treatment of oligoprogressive renal cell carcinoma.
Authors: Xinyue Zhang, Ruiqi Liu, Yang Liu, Zhiling Zhang, Jianming Gao, Shengjie Guo, Hui Han, Fangjian Zhou, Pei Dong, Liru He
Journal: Journal of Clinical Oncology (2024)

4540 Background: For metastatic renal cell carcinoma (mRCC) patients (pts) with oligoprogression, escalation of systemic therapy (STE) to the next line of treatment is one of the major strategies but not the only option. Our study aimed to investigate the safety and efficacy of stereotactic body radiotherapy (SBRT) to mRCC pts with oligoprogression after first-line systemic therapy. Methods: This is a single-arm, phase II study enrolling oligoprogressive mRCC pts, defined as ≤ 3 progressive lesions with total metastases ≤ 5, who have received first-line systemic therapy for more than three months (ChiCTR2000032947). No liver or brain metastasis was allowed. Nephrotic focus was treated before or after enrollment. Pts remained on current first-line systemic therapy and received SBRT for all the oligoprogressive lesions, with 35-45Gy in 5 fractions. If oligoprogressive lesions appeared &gt; 6 months after the end of SBRT, which were not irradiated, a second round of SBRT could be allowed. Primary endpoint was progression-free survival (PFS); secondary endpoints were local control (LC) rate, time to STE, overall survival (OS) and safety. Results: From June 2020 to Jan 2024, 30 pts were enrolled, and 27 pts (median age: 55 years; male-to-female ratio: 16:11) were evaluable for efficacy after SBRT. Most pts (74.1%) had a clear cell histology, and most pts (92.6%) were at an intermediate or a poor risk according to the International Metastatic RCC Database Consortium criteria. Sixteen pts had one progressive lesion and 11 pts had 2-3 lesions. The median time to oligoprogressive disease under first-line systemic therapy (mostly TKI monotherapy: 85.2%) was 13.6 months. The most common sites for SBRT were bone (32.4%), lymph node (23.5%) and lung (23.5%). At a median follow-up of 23.5 months, the LC rate was 97.1%. Six-month PFS, 12-month PFS, 18-month PFS, 24-month PFS and median PFS were 88.9%, 54.2%, 36.4%, 22.7% and 15.0 months, respectively. The 24-month OS and median OS were 78.5% and not reached. Grade 3-4 treatment-related adverse events (AEs) occurred in 44.4% pts, and the most common AEs were hematological toxicity (18.5%), hypertension (18.5%), and palmar-plantar erythrodysesthesia syndrome (7.4%). No SBRT-related grade 3-4 toxicity was observed. Conclusions: SBRT is a safe and an effective treatment for oligoprogressive mRCC, with a notable extension of the ongoing first-line systemic therapy. Clinical trial information: ChiCTR2000032947.
MEK inhibitor combined with RTK inhibitor (trametinib plus anlotinib) in non-G12C KRAS-mutant non-small cell lung cancer: A new strategy.
Authors: Baohui Han, Jun Lu, Hua Zhong, Tianqing Chu, Wei Zhang, Minjuan Hu, Chunlei Shi, Liwen Xiong, Aiqin Gu, Huimin Wang, Yuqing Lou, Yanwei Zhang, Runbo Zhong, Zhiqiang Gao
Journal: Journal of Clinical Oncology (2024)

8542 Background: It remains as a big challenge to provide therapeutic regime for the non-G12C KRAS-mutant non-small cell lung cancer (NSCLC) patients. The strategy of co-inhibition of MEK/RTKs pathways via trametinib and anlotinib showed preliminary activity in non-G12C KRAS-mutant NSCLC. Methods: The phase I clinical trial (NCT04967079) was divided into 2 parts including part A and part B. The primary endpoint of part A was to determine the recommended phase 2 dose (RP2D) and the primary endpoint of part B was to evaluate the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), disease control rate (DCR) and safety. Results: The part A containing 13 patients showed that the RP2D is trametinib (2 mg) plus anlotinib (8 mg), the ORR is 69.2%, the PFS is 207 days, DCR is 92% and the rate of adverse events (AEs) ≥ grade 3 is 23%. The part B containing 20 patients showed high efficacy of this combinational therapy (trametinib (2 mg) plus anlotinib (8 mg)), with the ORR at 65%, the PFS is 330 days, the DCR at 100%, and the rate of AEs ≥ grade 3 at 35%. An integrative analysis for the part A plus part B (33 patients) indicated that the ORR is 66.7%, the PFS is 300 days, the DCR is 97% and the rate of adverse events (AEs) ≥ grade 3 is 30%. Conclusions: This study provides a potential combinational therapeutic strategy for those non-G12C KRAS-mutant lung cancer patients via oral administration of trametinib and anlotinib. Clinical trial information: NCT04967079 .
A phase 1b study of ensartinib in combination with platinum-based chemotherapy and bevacizumab in ALK-positive non-small cell lung cancer (NSCLC).
Authors: Kyle Concannon, Giovanni Selvaggi, Joey Zhou, Yasir Y Elamin
Journal: Journal of Clinical Oncology (2024)

8624 Background: Ensartinib is an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), which has shown systemic and central nervous system efficacy in ALK-positive non-small cell lung cancer (NSCLC) and superiority over crizotinib in the first-line setting. This single-arm phase-1b study evaluates the efficacy of ensartinib in combination with platinum-based chemotherapy and bevacizumab in ALK-positive advanced NSCLC. Methods: Patients were treated with 4 cycles of induction ensartinib, carboplatin, pemetrexed, and bevacizumab before receiving maintenance ensartinib with or without bevacizumab and/or pemetrexed until disease progression or intolerable toxicity. Prior treatment with ALK-targeting agents and the presence of asymptomatic brain metastases were allowed. The primary endpoints were to determine safety of ensartinib in combination with carboplatin, pemetrexed, and bevacizumab and to determine the recommend phase 2 dose of ensartinib in this combination. Results: Between June 22, 2021, and August 15, 2022, 6 patients were enrolled into the study and treated with at least one dose of ensartinib in combination with platinum-based chemotherapy and bevacizumab. All patients were included in safety and efficacy analyses. The median age was 54.7y, 3/6 were female, 5/6 were never smokers, the median ECOG was 1, and 3/6 had brain metastases at enrollment. Participants received a median of 2 prior lines of therapy (range 0-3) and 4/6 received prior ALK TKI therapy: 2/6 two prior ALK TKIs, 2/6 three prior ALK TKIs. As of 12/1/2022, the maximum severity adverse event (AE) was grade 2 in 1/6 patients, grade 3 in 4/6 patients, and grade 5 in 1/6 - a therapy unrelated bronchopulmonary hemorrhage. Ensartinib-related grade 1, 2, and 3 AEs occurred in 1/6, 3/6, and 2/6 respectively. Dose reductions from 225mg daily to 200mg daily occurred in 1/6 patients secondary to grade 3 transaminitis, which was subsequently well tolerated. 1/6 patients transitioned therapy after a treatment unrelated bowel perforation. The median time on trial was 9.6 months. 2/6 patients remained on treatment at time of censorship with trial durations of 22.6 and 15.8 months. 1/6 patients progressed and 2/6 patients died on treatment. Conclusions: Ensartinib in combination with platinum-based chemotherapy and bevacizumab had an acceptable safety profile and demonstrates clinical activity in treatment naïve and previously treated advanced ALK-positive NSCLC, including in patients treated with prior ALK-targeted therapies. Next phase study designs are currently being considered. Clinical trial information: 2020-0838.
Anlotinib plus docetaxel in advanced NSCLC progressing on immunotherapy: A pooled analysis of two randomized trials.
Authors: Lin Wu, Yong Fang, Xingxiang Pu, Jiawei Shou, Zemin Xiao, Jun Chen, Maoliang Xiao, Qunyi Guo, Zhongsha Ma, Wei Hong, Qianzhi Wang, Yonghui Wang, Jia Li, Chuangzhou Rao, Weng Jie, Liqin Lu
Journal: Journal of Clinical Oncology (2024)

8062 Background: This analysis aimed to evaluate outcomes of anlotinib plus docetaxel versus docetaxel alone in patients with advanced non-small cell lung cancer (NSCLC) after progression on immune-checkpoint inhibitors (ICIs) using the pooled data from two randomized trials (ALTER-L016; ALTER-L018). Methods: Eligible patients for this pooled analysis were aged 18-75 years and had EGFR/ALK/ROS1 wild-type advanced NSCLC progressing after first-line ICIs therapy. Patients were randomly assigned to receive anlotinib (10 mg [L016] or 12 mg [L018] once daily on days 1-14) plus docetaxel (60 mg/m 2 [L016] or 75 mg/m 2 [L018], on day 1 every 3 weeks) or docetaxel alone. The primary endpoint was progression-free survival (PFS). Second endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Total of 71 patients (L016, n = 39; L018, n = 32) who progressed after ICIs were included in this pooled analysis, 40 of whom had received anlotinib plus docetaxel and 31 received docetaxel. Median follow-up for all patients was 27.0 months (IQR, 17.6-31.2). A significant PFS benefit was observed with anlotinib plus docetaxel (5.4 months; 95% CI, 5.0-9.3) over docetaxel alone (2.3 months; 95% CI, 1.4-2.9), with a hazard ratio (HR) of 0.34 (95% CI, 0.18-0.63; P &lt; 0.001). Improvement in PFS was seen across most evaluated subgroups. Anlotinib plus docetaxel induced a higher ORR (25.0% vs. 12.9%) and DCR (82.5% vs. 45.2%) over docetaxel alone. Median OS was similar between two arms (16.2 vs. 13.7 months; HR = 0.82 [0.47-1.44]; P = 0.488). Subsequent therapy with ICIs was associated with a longer OS. The incidence of grade 3 or higher treatment-related adverse events was 32.5% with anlotinib plus docetaxel and 6.5% with docetaxel. Conclusions: Anlotinib plus docetaxel demonstrated survival and response improvements compared with docetaxel alone in patients with advanced NSCLC progressing after ICIs, with a manageable safety profile. This finding suggested anlotinib plus docetaxel might be effective and safe option in this setting. Clinical trial information: NCT03726736 ; NCT03624309 .
Author Correction: Adipose tissue macrophages secrete small extracellular vesicles that mediate rosiglitazone-induced insulin sensitization
Authors: Theresa V Rohm, Felipe Castellani Gomes Dos Reis, Roi Isaac, Cairo Murphy, Karina Cunha E Rocha, Gautam Bandyopadhyay, Hong Gao, Avraham M Libster, Rizaldy C Zapata, Yun Sok Lee, Wei Ying, Charlene Miciano, Allen Wang, Jerrold M Olefsky
Journal: Nature Metabolism (2024)
18F-THK5351 Uptake May Not Estimate Neurofibrillary Tangles in In Vivo Images
Authors: Kenji Ishibashi, Tetsuro Tago, Masashi Kameyama, Jun Toyohara, Kenji Ishii
Journal: Clinical Nuclear Medicine (2024)

Abstract Currently, monoamine oxidase B is recognized as the primary target of 18 F-THK5351, although 18 F-THK5351 was initially developed to target neurofibrillary tangles (NFTs) in Alzheimer disease. When clinically applying 18 F-THK5351 PET to visualize ongoing astrogliosis via estimating monoamine oxidase B levels, a crucial concern is how much degree 18 F-THK5351 uptake reflects NFTs in in vivo images. To unravel this concern, a head-to-head comparison between 18 F-THK5351 and 18 F-MK-6240 (estimating NFT) images in the NFT lesion ideally without accompanying astrogliosis is essential. Here, we present such a case suggesting that 18 F-THK5351 uptake may not estimate NFTs in in vivo images.
Skull Base Aspergillus Infection Mimicking Tumor Recurrence
Authors: Tzyy-Ling Chuang, Yuh-Feng Wang
Journal: Clinical Nuclear Medicine (2024)

Abstract We report a case of recurrent nasopharyngeal carcinoma postnasopharyngectomy, presenting with headaches. MRI revealed abnormal signals of the clivus with enhancement, and FDG PET/CT indicated intense uptake in the nasopharynx, clivus, and left neck lymph nodes. Bone SPECT/CT showed bony erosion and uptake in bilateral skull base areas. Biopsy confirmed aspergillosis. Despite the challenges in distinguishing tumor invasion from Aspergillus infection on MRI, bone SPECT/CT, and FDG PET/CT, the short postsurgery period and extensive uptake suggested skull base osteomyelitis.