bluuebunny/crossref_metadata_2025_split huggingface dataset:
Off-label use of checkpoint inhibitor (CPI) monotherapy in PD-L1–negative or unknown recurrent/metastatic head and neck cancer (R/M HNSCC).
Authors: Stalker Margaret , Qu Kewen , Hwang Wei-Ting , Cohen Roger B. , Mamtani Ronac , Sun Lova 
Published: June 2024

6025 Background: The KN-048 study established that the CPI pembrolizumab with chemotherapy should be used for PD-L1 negative R/M HNSCC, while CPI monotherapy has limited efficacy (ORR 4%) in PD-L1 negative disease and should be reserved for PD-L1 positive disease. National patterns of PD-L1 testing and PD-L1 guided treatment selection are unknown. We examined PD-L1 testing rates, the use of CPI overall, and the use of CPI monotherapy in PD-L1 negative or unknown R/M HNSCC (“off-label”), and associated factors. Methods: This retrospective analysis included adult patients starting treatment for R/M HNSCC from 2019-2023 in the Flatiron Health electronic health record (EHR)-derived de-identified national database. Demographics, treatment type, and PD-L1 test results were summarized using descriptive statistics. Specifically, first-line therapy was categorized as CPI monotherapy, CPI with chemotherapy, or chemotherapy and/or cetuximab without CPI. “Off-label” use of CPI was defined as single-agent use without concurrent chemotherapy in patients with negative or unknown PD-L1. Factors associated with “off-label” use were identified using multivariable logistic regression analysis. Results: Our cohort included 3,395 patients with median age 66 (IQR 59-73), 65% White, 77% treated in a community setting, 76% with smoking history, 37% HPV positive, and 72% ECOG PS 0-1. Almost half of patients (44%) did not have a recorded PD-L1 test result; of those with known PD-L1 status (n=1886), distribution of combined positive score (CPS) 0, 1-19, and 20 was 19%, 41%, and 40%, respectively. The most common frontline treatment was CPI monotherapy (43%), followed by chemotherapy/cetuximab (33%) and CPI with chemotherapy (25%). CPI monotherapy use was highly prevalent in patients aged ≥75 (54%) and with ECOG PS ≥ 2 (52%). Among the subgroup of PD-L1 negative or unknown patients (n=1831), 37% (678) received CPI monotherapy (“off-label”). Factors associated with “off-label” CPI monotherapy use included ECOG PS ≥ 2 (OR 1.3), age ≥ 75 (OR 1.3), community practice (OR 1.7), and earlier year (HR 1.2) (all p<0.05). Conclusions: Most US patients with R/M HNSCC are now receiving CPI-based therapy in the frontline setting, but PD-L1 testing rates remain suboptimal. Use of CPI monotherapy in PD-L1 negative or unknown HNSCC is common, particularly in elderly patients and those with poor performance status.[Table: see text]
Safety and efficacy of iparomlimab and tuvonralimab in combination with gemcitabine and cisplatin as first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma: A multicenter, single-arm, phase 2 trial (DUBHE-N-302).
Authors: Huang Yan , Zhao Shen , Qu Song , Guan Ying , Zhao Yuanyuan , Wang Jie , Wu Ting , Yu Xiaokui , Xue Shilin , Kang Xiaoyan , Zhang Li 
Published: June 2024

6026 Background: Programmed cell death 1 (PD-1) inhibitor plus chemotherapy has been the standard first-line (1L) treatment for patients with recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Iparomlimab and tuvoralimab (QL1706), a novel bispecific antibody targeting PD-1 and cytotoxic T-lymphocyte antigen 4, indicated promising anti-tumor activity for advanced solid tumors including NPC in phase 1/1b trial. This study aimed to evaluate the safety and efficacy of QL1706 combined with chemotherapy as 1L treatment in R/M NPC. Methods: This multicenter, single-arm, phase 2 study (NCT05576272) recruited patients with NPC who had no prior systemic therapy in the R/M setting. Intravenous injection of QL1706 5 mg/kg (day 1) combined with gemcitabine 1000 mg/m² (days 1 and 8) and cisplatin 80 mg/m² (day 1) was administered for four to six cycles (21 days per cycle), followed by maintenance treatment of QL1706. The primary endpoint was safety and tolerability. Key secondary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS). Results: From May 19 2022 to Dec 9 2022, 29 patients were included. The median age was 50 years (range, 25-65), with 24 (83%) being male. Seven patients (24%) had an Eastern Cooperative Oncology Group Performance Status of 1. Nineteen (66%) had recurrent disease. As of the data cut-off on Dec 31 2023, the median follow-up was 15.5 months. Treatment-related adverse events (TRAEs) occurred in 29 patients (100%). TRAEs of grade 3 or 4 occurred in 18 patients (62%), with the most common being decreased neutrophil count (41%), decreased white blood cell count (35%), anemia (21%), and decreased platelet count (21%). Twenty patients (69%) experienced immune-related adverse events, with the most common being grade 1-2 hypothyroidism (38%). Serious TRAEs occurred in five patients (17%). Three patients (10%) discontinued treatment due to adverse events. No treatment-related deaths occurred. Among the 28 evaluable patients, the ORR was 82.1% (95% confidence interval [CI], 63.1% to 93.9%), including one achieving complete response. The DCR was 96.4% (95% CI, 81.7% to 99.9%). The median PFS was 12.5 months (95% CI, 5.7 to not evaluable [NE]), and the median DoR was 14.1 months (95% CI, 7.6 to NE). In 14 patients with high expression level of programmed cell death ligand 1 (combined positive score≥50), the median PFS was 16.2 months (95% CI, 9.9 to NE). The median OS was not reached. Conclusions: Iparomlimab and tuvoralimab combined with chemotherapy showed tolerable safety and promising efficacy as 1L treatment for patients with R/M NPC. Clinical trial information: NCT05576272 .
Anti-LAG-3 antibody LBL-007 in combination with anti-PD-1 antibody tislelizumab with or without chemotherapy in patients with advanced nasopharyngeal cancer and other malignant tumors: A phase Ib/II dose escalation/expansion study.
Authors: Yang Yunpeng , Chen Yu , Qu Song , Liu Lei , Chen Lisha , Yang Kunyu , Huang Xiaoming , Li Jingao , Wang Rensheng , Zhu Haisheng , Zhao Shiwei , Li Tao , Cai Shengli , Zhang Li 
Published: June 2024

6033 Background: Dual inhibition of PD-1 and LAG-3 is expected to synergistically increase immune response against tumor growth while chemotherapy can enhance the efficacy of immunotherapy through various mechanisms. Here we report the safety and efficacy of LBL-007 (anti-LAG-3) in combination with tislelizumab (anti-PD1) with or without chemotherapy in advanced solid tumors (Phase Ⅰb) and previously untreated patients with advanced nasopharyngeal carcinoma (NPC) (Phase II). Methods: In phase Ⅰb, patients with relapsed and refractory advanced solid tumor received LBL-007 (300 or 600 mg) plus tislelizumab (200 mg) (both i.v. Q3W), and in phase Ⅱ, patients with previously untreated recurrent or metastatic NPC patients received LBL-007 (600 mg) plus tislelizumab (200 mg) in combination with GC chemotherapy [gemcitabine (1000 mg/m2) and cisplatin (80mg/m2)] (i.v. Q3W). The primary endpoints were tolerability, safety, and efficacy. Results: Updated data with more follow up including duration of response and progression free survival will be available to report at the meeting. As of January 10, 2024, 21 patients (4 NPC, 7 NSCLC, 7 melanoma and 3 others) and 42 NPC patients were enrolled in in phase Ⅰb and phase Ⅱ respectively. The median follow-up was 13.1 months. During the study, no Dose limiting Toxicity (DLT) was observed, and Recommended Phase 2 Dose (RP2D) was determined to be 600mg Q3W for both chemo and chemo free regimens. In phase II, all grades TRAEs occurred in 39 patients (92.9%), with grade ≥3 TRAE in 24/42 patients (57.1%). The most common TRAEs (≥20%) included white blood cell count decreased, neutrophil count decreased, anaemia, ALT increased, AST increased, platelet count decreased, nausea, hyponatraemia, hypochloraemia, blood creatinine increased, vomiting, and hypothyroidism. Treatment interruption due to TEAEs occurred in 31 (73.8%) patients. 13 patients (31%) experienced SAEs. 1 patient experienced Grade 5 AE due to exacerbation of cachexia unrelated to LBL-007/tislelizumab. The clinical efficacy is shown in the table. Conclusions: LBL-007/tislelizumab combination is well-tolerated in patients with advanced malignant tumors. LBL-007/tislelizumab/GC combination showed manageable, no new safety concerns and encouraging antitumor activity in previously untreated and advanced NPC patients. The encouraging efficacy and safety profile may support a pivotal study with LBL-007 in combination with tislelizumab and GC chemotherapy for NPC development in 1L setting. Clinical trial information: NCT05516914 . [Table: see text]
Four-year overall survival follow-up and dynamic EBV titer analysis of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (r/m NPC).
Authors: Chen Qiu-Yan , Mai Hai-Qiang , Chen Dong-Ping , Hu Chao-su , Yang Kunyu , Wen Jiyu , Li Jingao , Shi Yingrui , Jin Feng , Xu Ruilian , Pan Jian-ji , Qu Shenhong , Li Ping , Hu Chunhong , Liu Yi-Chun , Jiang Yi , He Xia , Wang Hung-Ming , Lim Darren Wan-Teck , Xu Rui-Hua ,   Coherus Biosciences and Shanghai Junshi Biosciences
Published: June 2024

6039 Background: In October 2023, the US FDA approved toripalimab in combination with Gemcitabine-Cisplatin (GP) as first-line treatment for recurrent or metastatic (r/m) NPC based on the results of JUPITER-02 study (NCT03581786). Here we report the results of four-year overall survival (OS) follow-up and dynamic EBV DNA copy number and its correlation with clinical outcome. Methods: Patients with r/m NPC (n=289) were randomized (1:1) to receive toripalimab 240 mg (n=146) or placebo (n=143) in combination with GP once every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG performance score (0 vs. 1) and extent of disease (recurrent vs.primary metastatic). The primary endpoint was progression free survival by an independent review committee. Secondary endpoints included OS and safety. Exploratory endpoints included dynamic blood EBV DNA copy number and its correlation with clinical efficacy. Results: By the cutoff date of January 9, 2024, 50 months after the last patient was enrolled, 150 deaths were recorded. Compared with the results from the final OS analysis, consistent survival improvement was observed for toripalimab over placebo: HR=0.61 (95% CI: 0.44-0.85), nominal p=0.0027. The median OS was not yet reached in the toripalimab arm and was 33.7 months in the placebo arm. The 5-year OS rates were 52.0% in the toripalimab arm, and 33.9% in the placebo arm. Among patients with detectable baseline EBV DNA copy number and at least one EBV result after study treatment, significantly more patients from the toripalimab arm had EBV DNA copy number decreased to undetectable level than those in the placebo arm, 96.3% vs. 84.5%, p= 0.004. In addition, significantly less patients experienced EBV DNA copy number rebound in the toripalimab arm than in the placebo arm after the initial reduction, 36.5% vs, 57.4%, p=0.002. The median time from the lowest EBV DNA copy number to the rebound was 20.5 vs. 6.0 months in the toripalimab and placebo arms respectively. The rebound also preceded investigator-assessed disease progression by a median of 1.9 months in the toripalimab arm. Conclusions: The combination of toripalimab and chemotherapy showed long term survival benefit than chemotherapy alone with a 5-year OS rate at 52%. EBV DNA copy number might be used to monitor clinical response and predict disease progression. Clinical trial information: NCT03581786 .
An open-label, single-center phase II trial of cadonilimab (an anti-PD-1/CTLA-4 bispecific antibody) in combination with platinum-based dual-drug neoadjuvant chemotherapy for locally advanced, resectable head and neck squamous cell carcinoma.
Authors: Cao Fei , Wu Di , Xu PengFei , Fang Qi , Zhao Zheng , Zhang Xinrui , Yan Honghong , Jiang Ke , Zhou Jian , Li Yan , Lu Li-Xia , Chen Chunyan , Han Fei , Li Zhiming , Liu Xuekui 
Published: June 2024

6044 Background: Consensus on neoadjuvant treatment strategies for resectable head and neck squamous cell carcinoma (HNSCC) is not proposed currently. Preclinical and clinical findings suggested that PD-1/CTLA-4 bispecific antibodies may have synergistic anti-tumor activity. This study aimed to explore the safety and activity of cadonilimab in combination with platinum-based dual-drug neoadjuvant chemotherapy in locally advanced, resectable HNSCC. Methods: In this open-label phase II trial, eligible patients with untreated locally advanced, resectable HNSCC (T2N2-3M0、T3-4N0-3M0; stage III-IV, AJCC 8th Edition) were enrolled to receive cadonilimab (10 mg/kg) and platinum-based dual-drug [docetaxel (75 mg/m2) plus cisplatin (60 mg/m2)] on day 1 of each 21-day cycle for three cycles, followed by surgery and postoperative adjuvant therapy. The primary endpoint was objective response rate (ORR) per RECIST1.1. Secondary endpoints included pathologic complete response (pCR), safety, disease-free survival (DFS), and overall survival (OS). Results: Between July 2023 and December 2023, 24 patients were enrolled (median age, 55 years [range 34–69]; 21 men [87.5%]), tumors were located in the oral cavity (10/24, 41.7%), hypopharynx (8/24, 33.3%) and larynx (6/24, 25.0%), 20 (83.3%) patients were clinical T3/4 while 10 patients (41.7%) ≥N2 . After completion of neoadjuvant therapy, the ORR was 87.5% (21/24). Of the 24 patients, 12 (50.0%) patients reached pCR. Treatment-related adverse events (TRAEs) occurred in 14 (58.3%) patients. Grade 3-4 TRAEs were reported in 4 (16.7%) patients, including rash (12.5%), pruritus (12.5%) and Guillain-Barre syndrome (4.2%). DFS and OS data were not yet mature as of the cutoff date (January 1,2024). Conclusions: Cadonilimab plus platinum-based dual-drug neoadjuvant chemotherapy achieved favorable ORR and pCR with manageable toxicities in patients with HNSCC. Follow-up is still underway to obtain long-term survival data. Clinical trial information: NCT06023875 .
Neoadjuvant tislelizumab with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-1): An open-label, single-arm, phase 2 study.
Authors: Wei Zhigong , Chen Huijiao , Cai Lei , Chen Fei , Liu Jun , Peng Xingchen 
Published: June 2024

6073 Background: For patients with locally advanced head and neck squamous cell carcinoma (HNSCC), even receiving surgery with adjuvant radiotherapy or chemoradiotherapy, those remain at high risk of recurrence or metastasis. Neoadjuvant immunotherapy has been used in HNSCC, but provides only modest pathological response. Given single agent activity and unique mechanism of action of immune checkpoint inhibitors and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), we aimed to evaluate the antitumour activity and safety of neoadjuvant PD-1 blockade with EGFR inhibition in locally advanced HNSCC. Methods: This open-label, single-arm, phase 2 trial was done at a a tertiary hospital in China. Eligible patients were aged 18 years or older and had resectable HNSCC disease, had an Eastern Cooperative Oncology Group performance status of 0–1, had at least one measurable target lesion according to the RECIST 1.1, had no prior antitumor therapy for HNSCC. Patients received neoadjuvant treatment with intravenous tislelizumab (200 mg) on the first day of each 3 week, with totally two cycles and orally afatinib (30 mg) starting on the first treatment day and ending on the day before surgery, with totally six weeks, and then patients proceeded to receive surgical resection. The primary endpoint was major pathological response, defined as the presence of 10% or less residual viable tumour at the time of surgery. Results: A total of 25 patients were enrolled completed the neoadjuvant therapy. Eight of 23 evaluable patients exhibited a major pathological response (MPR) (35%; 95% confidence interval [CI], 16%—57%), of which four had a complete pathological response of primary tumor (17%, 95%CI, 5%—39%). The overall response rate was 48% (12/25, 95%CI: 28%—69%) and disease control rate was 100% (25/25, 95%CI: 86%—100%). Common grade 3—4 adverse events included diarrhea (5/25 [20%]), hypokalemia (4/25 [16%]) and rash (3/25 [12%]). No treatment related fatalities were observed. Immunologically, post-neoadjuvant treatment demonstrated increased CD3, CD8, and CD56 expression within the tumor microenvironment. The increase of CD8 and CD56 expression level was significant higher in patients achieving MPR, along with elevated circulatory NK cells at baseline, compared to those in patients achieving non-MPR. Conclusions: This study underscores encouraging antitumor activity, manageable toxicity profile and promising immune activation elicited by neoadjuvant tislelizumab plus afatinib for HNSCC, which deserves further assessment. Clinical trial information: NCT05517330 .
Relationship between infiltration of tissue-resident memory T cells (TRM) in head and neck squamous cell carcinoma (HNSCC) tissue and localization and age.
Authors: von Witzleben Adrian , Ellis Matthew , Thomas Gareth , Hoffmann Thomas K , Laban Simon , Ottensmeier Christian H.H 
Published: June 2024

6089 Background: Elevated levels of tumor-infiltrating lymphocytes (TILs) have been correlated with improved survival rates in cancer patients. Among TIL subgroups, tissue-resident memory T cells (TRM, CD8+CD103+) are recognized as pivotal contributors to the anti-cancer immune response. In this study, we aimed to evaluate TRM presence in Head and Neck Squamous Cell Carcinoma (HNSCC) tissue utilizing a developed tissue microarray (TMA) and a multiplex immunohistochemistry (MxIHC) approach. Methods: HNSCC cases from Southampton Hospital spanning the years 2000 to 2016 were reviewed, resulting in the identification of approximately 300 cases with sufficient primary tumor material. A TMA was constructed by triplicate coring of marked tumor areas on all slides. Subsequently, MxIHC, incorporating markers such as CD8 and CD103, was performed using a stain-scan-strip methodology. Digital image analysis software was employed to analyze scanned slides, and a quality check (QC) was conducted. Results: Following QC, 193 primary tumors remained (hypopharynx and larynx: n = 28, lip and oral cavity: n = 51, oropharynx: n = 114). Significantly higher counts of CD8 T cells and TRM were observed in the combined group of oropharynx, lip and oral cavity compared to the combined group of larynx and hypopharynx. This significance persisted even after excluding HPV negative oropharynx cases. HNSCC of the lip and oral cavity itself had statistically more TRM than larynx and hypopharynx. No differences were found in the subgroups between tonsil and tongue base. Stratifying the analysis by age revealed a statistically significant increase in TRM infiltration in HNSCC among young patients (≤50 years) compared to the 51-60 years and 61-70 years age groups, a pattern not observed for CD8 alone. Conclusions: This study underscores the importance of HNSCC heterogeneity and highlights the impact of age on immune infiltration, emphasizing the unique contribution of TRM in the anti-cancer immune response.
Estimating the health care costs associated with receipt of lisocabtagene maraleucel: Insights from adults with mantle cell lymphoma (TRANSCEND NHL 001).
Authors: Phillips Tycel Jovelle , Martin Ashley , Lee Abraham D. , Mirza Sana , Carattini Thomas , McGarvey November H. , Patwardhan Pallavi 
Published: June 2024

7028 Background: Anti-CD19 CAR T cell therapy is a major advancement for treating R/R B-cell malignancies such as mantle cell lymphoma (MCL). While effective disease management with CAR T cell therapy is expected to reduce patients’ health care resource utilization (HCRU) over the long-term, few studies have examined the short-term impacts of this treatment on HCRU and associated health care costs. Here, we used data from the TRANSCEND NHL 001 (NCT02631044) clinical trial to estimate the HCRU-related costs incurred by patients with R/R MCL over the first 12 months after receipt of lisocabtagene maraleucel (liso-cel). Methods: A retrospective analysis of clinical trial data was conducted to calculate the frequency of HCRU (medications [excluding liso-cel], diagnostics, procedures, ICU and non-ICU hospitalizations) observed over the 12 months immediately after administration of liso-cel. Costs for each HCRU event were derived from public databases and literature, adjusted to 2023 United States (US) dollars, and used to estimate patient-level health care costs. Results: Of the patients treated (N = 88), 76.1% were male, 87.5% were White, and mean ± standard deviation (SD) age was 67.5 ± 9 years. All patients were treated in the US and completed a median (range) of 3 (1–11) prior lines of therapy before receiving liso-cel. Most patients (93.2%) received the recommended dose of 100 × 106 CAR+ T cells. The total mean ± SD per-patient cost (excluding liso-cel) was estimated at $138,413 ± $58,555 over 12 months. Facility use accounted for 77.7% of all costs, primarily owing to non-ICU hospitalizations (98.9%), which had a mean ± SD length of stay of 19.5 ± 16.7 days per eligible patient. Half of all health care costs were incurred within the first month of infusion (53.2%), with each subsequent month contributing a fraction (1.5%–6.3%) of total costs. A total of 13 out of 88 patients received their initial infusion in an outpatient setting and incurred 23% fewer costs compared with those who received their infusion in an inpatient setting ($110,050 vs $143,418), primarily as a function of reduced first-month facility use. Total costs for patients receiving liso-cel in outpatient settings were further reduced to $72,771 upon exclusion of 3 outliers. Conclusions: Non-ICU hospitalizations were the largest driver of liso-cel–related costs in this R/R MCL cohort of clinical trial participants. Most of the cost burden was incurred within 1 month of treatment, with dramatic reductions in HCRU and health care costs observed thereafter. Results suggest that treatment in the outpatient setting, even in part (eg, at initial infusion only), may confer substantial cost savings to the health care system.