bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, efficacy and biomarker data in patients with non-small cell lung cancer treated with the anti-IL1RAP antibody nadunolimab in combination with platinum doublet.
Authors: Paz-Ares Luis G. , Paulus Astrid , Zemaitis Marius , Cicenas Saulius , Zvirbule Zanete , Felip Enriqueta , Sanfridson Annika , Rydberg-Millrud Camilla , Magnusson Susanne , Losic Nedjad , Garcia-Ribas Ignacio 
Published: June 2023

9089 Background: Interleukin-1 Receptor Accessory Protein (IL1RAP), expressed in various tumors, is essential for IL-1α and IL-1β signaling. IL-1α/IL-1β are implicated in tumor progression and therapy resistance, and chemotherapy can upregulate IL-1α in e.g. non-small cell lung cancer (NSCLC). Nadunolimab (CAN04), a fully humanized ADCC-enhanced IgG1 antibody, targets IL1RAP and blocks IL-1α/IL-1β signaling. Here, data are reported from clinical phase 1/2 trials in NSCLC pts given nadunolimab and platinum doublet. Methods: Pts with advanced NSCLC, 1st line or progressed on pembrolizumab, received nadunolimab at 1 (n=16), 2.5 (n=3) or 5 mg/kg (n=11) with cisplatin/gemcitabine (NCG), or at 2.5 mg/kg with carboplatin/pemetrexed (NCP) (n=5). Four additional pts, 3rd line or beyond, received NCG at 1 or 1.75 mg/kg nadunolimab. Primary objective was safety; efficacy was evaluated as a secondary objective and effects on serum and tumor tissue biomarkers explored. Results: The 30 1st or 2nd line pts given NCG had a median PFS of 7.2 months (95% CI 5.5-8.2), ORR of 53% (34-72) and DoR of 5.8 months (3.7-7.5). A dose-response trend was observed for PFS and DoR (Table). Twenty non-progressing pts continued nadunolimab as monotherapy post chemo; 8 of these remained in disease control for a further 12-131 wks. Nadunolimab monotherapy was well tolerated with ≥grade 3 adverse events reported less frequently. Two pts (non-squamous, 2nd line post pembrolizumab) showed complete responses, one observed after >40 wks of nadunolimab monotherapy. Furthermore, confirmed partial responses were observed in 3 of 5 pts given NCP, and 2 of 4 3rd line or beyond pts given NCG. NCG reduced several serum markers, e.g. CRP and tumor-promoting HGF, effects which were maintained by nadunolimab monotherapy. Additionally, a decrease of MCP-3 and 4 was observed during monotherapy. NCG also reduced IL-1- and tumor microenvironment (TME)-related markers in serum (angiopoietin 1, CXCL5, IL-8, TWEAK and VEGFA). Spatial analyses of protein and RNA markers in tumor biopsies are ongoing to verify potential effects in the TME. Conclusions: NCG shows promising efficacy in NSCLC with a trend for dose response, and long-term disease control by nadunolimab monotherapy post chemo with good safety. These observations are supported by changes in TME-related serum biomarkers. Preliminary data suggest similar efficacy with NCP, and in more heavily pretreated pts. Clinical trial information: NCT03267316 , NCT05116891 . [Table: see text]
RET testing and treatment patterns among patients with aNSCLC in US clinical practice.
Authors: Kim Eunice , Sussell Jesse , Ng Carmen , Nedzesky Justin , Zhang Qing , Ngiam Celina , Mansfield Aaron Scott 
Published: June 2023

9091 Background: Biomarker testing, including for rearrangement during transfection (RET), is recommended and important in selecting efficacious targeted therapy for patients with advanced non-small cell lung cancer (aNSCLC). This retrospective cohort study characterized RET testing and treatment patterns among aNSCLC patients in clinical practice. Methods: We used the nationwide Flatiron Health electronic health record-derived de-identified database to select patients diagnosed with aNSCLC (stage ≥IIIB) from 2017-2022. We measured rates of RET testing (test result ≤90 days after advanced diagnosis). We used logistic regression to identify baseline characteristics predictive of timely testing. Finally, we described treatment patterns for patients with RET+ aNSCLC before and after the US approval of RET inhibitors. Results: Among 26,329 aNSCLC patients, rates of RET testing ≤90 days after advanced diagnosis increased from 25% (2017 Q1) to 73% (2022 Q1). Patients were less likely to receive RET testing within 90 days if they were Black (multivariate odds ratio [OR] 0.8) or Hispanic (OR 0.8) compared to White, or had Medicare (OR 0.9; all p<0.001) compared to commercial insurance. Patients were more likely to receive RET testing within 90 days if they were in the highest socioeconomic quintile (OR 1.4), had de novo disease (OR 2.1), or no history of smoking (OR 1.3; all p<0.001). Between 2017 and 2022, there were increases in the use of next-generation sequencing (66% to 89%) and blood samples for biomarker testing (25% to 49%) and a decrease in mean days from diagnosis to test result (33 to 28) for the first RET test among those who had testing within 90 days. Among all patients with aNSCLC tested within 90 days (n=12,275), 73 were RET+ and received 1L treatment ≤90 days after advanced diagnosis. The most common 1L treatments before (n=35) and after (n=38) RET inhibitor approval were chemotherapy (40%) and RET inhibitor (42%), respectively (Table). Conclusions: RET testing has increased over time, but certain patient subgroups are less likely to receive timely RET testing and therefore may not be optimally treated. Among patients with RET+ aNSCLC identified after RET inhibitor approval, only 42% were treated with a RET inhibitor in the 1L setting. These results suggest both disparities in access to RET testing and unmet medical need among patients with RET+ aNSCLC. [Table: see text]
Explore ALK: Alectinib activity in patients with ALK+ metastatic non-small cell lung cancer—A national real world analysis (GFPC 03-2019).
Authors: Swalduz Aurélie , Rousseau-Bussac Gaelle , Guisier Florian , Doubre Helene , Fournel Pierre , Falchero Lionel , Bigay Game Laurence , Veillon Remi , Marcq Marie , Ricordel Charles , Decroisette Chantal , Dano Domitille , Justeau Gregoire , Martinez Stéphanie , Cortot Alexis B , Morel Hugues , Greillier Laurent , Descourt Renaud 
Published: June 2023

9092 Background: Alectinib is a standard of care option in advanced ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients (pts), with efficacy established by phase 3 trials, in first-line and beyond. There are few efficacy data in unselected populations. Methods: The objective of this study was to evaluate the efficacy of alectinib in real-world setting. All ALK+ advanced NSCLC pts initiating alectinib, between December 13, 2017 (date of access in France) and June 27, 2020, whatever the line, were included in explore ALK study. Patient characteristics, alectinib duration of treatment (DOT), progression-free survival assessed locally (rwPFS), overall survival (OS) according to the prescription line of alectinib, the presence of brain metastases at alectinib initiation, response rate and tolerance were collected from the medical files. Results: The analysis included 223 pts: 46.2% were men, 84.7% had no smoking history or were former smokers, median age was 59 (22-101) years and 95% were adenocarcinomas. Alectinib was initiated as first-line treatment in 119 pts, with a PS of 0/1/>1 in 42%/31%/27% of cases, a median number of metastatic sites of 2 (cerebral, hepatic, bone in 33%, 24% and 32% of cases). In first-line setting, after a median follow-up of 33.7 months (95%CI, 32.2-37.5), the median of rwPFS and DOT were 28.1 (95%CI, 20.7-40.4) and 26.9 (95%CI, 20.2-31.3) months, respectively. The median OS was not reach (NR), the 3-year OS rate was 72.1%. The rwPFS was not significantly different depending on whether or not the patient has brain metastases, 28.1 (95% CI, 14.5-NR) and 30.5 (85% CI, 18.9-40.4) months, respectively. The best response was complete (CR), partial (PR) and stable (SD) in 21%, 58% and 17%. The cerebral response, evaluable in 30/39 of the pts, was CR, PR and SD in 26%, 46% and 23% respectively; 33% of pts had a grade 3 adverse event, resulting in a temporary interruption of treatment in 7.6% of cases and a permanent discontinuation in 5.9% of cases. At the time of progression, 48.1% of pts had a new biopsy (66% of tissue biopsy). Efficacy data for alectinib prescribed as second line and above are summarized in the table. Conclusions: In this large real-world, cohort of unselected advanced ALK+ NSCLC pts, alectinib initiated in 1st-line or beyond provides similar efficacy and safety results as obtained in phase III clinical trials. [Table: see text]
Long-term outcome for patients with advanced non‒small-cell lung cancer treated by autologous cytokine-induced killer (CIK) cell immunotherapy in combination with sintilimab plus chemotherapy: NSCLC-CCICC-002.
Authors: Liu Liang , Zhou Li , Ren Xiubao , Zhang Weihong , Xiong Yanjuan ,   CCICC
Published: June 2023

9096 Background: Autologous cytokine-induced killer (CIK) cell immunotherapy in combination with Sintilimab demonstrated robust antitumor activity and safety in the phase Ib CCICC-002 study (NCT03987867) of Non‒Small-Cell Lung Cancer. Long-term outcomes in patients are reported herein. Methods: Systemic therapy naïve patients received platinum-based doublet chemotherapy, Sintilimab (PD1 inhibiter), and CIK cells every 3 weeks for 4 cycles, then maintenance treatment with Sintilimab in squamous and with Sintilimab plus pemetrexed in non-squamous NSCLC until disease progression or unacceptable toxicity or two years. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. OS and PFS were based on immune-related response criteria by investigator assessment (data cut-off, January 31, 2023). Results: From May 2019 to Jan 2021, CCICC-002 enrolled 33 patients（19 squamous, 14 non-squamous NCSLC; 1 patient was excluded because the second biopsy revealed EGFR mutation) aged 46-73 years with median follow-up was 31.4 months (range, 7.6-44.4 months). Estimated 3-year OS was 51.8% in all patients; median OS was not reached (95% CI, 26.6 months-not reached) in all patients. In subgroups, median OS was 27.6 months (95% CI, 13.4 months-not reached) in squamous NCSLC and not reached (95% CI, 29.9 months-not reached) in non-squamous NCSLC, respectively. Median OS was not reached (95% CI, 27.6 months-not reached) in PD-L1 positive patients and 28.3 months (95% CI, 15.6 months-not reached) in PD-L1 negative patients, respectively. Estimated 3-year PFS rate was 27.5% and median PFS was 17.9 months (95% CI, 8.2-26.5 months) in all patients. Median PFS was 17.3 months (95% CI, 5.0-24.0 months) in squamous NCSLC and 22.4 months (95% CI, 5.7 months-not reached) in non-squamous NCSLC, respectively. Median response duration was 18.7 months (95% CI, 10.1-27.6 months). 30.3% of patients were ongoing at data cut-off, and the longest response was ongoing at 41.3 months. 1 of the 5 CMR (complete metabolic response by PET-CT) patients experienced disease progression during observation. Treatment-related AEs (TRAEs) occurred in 94.0% of patients and resulted in study discontinuation in 7.8%, and 15.2% experienced grade 3/4 TRAE. Conclusions: This long-term analysis of CCICC-002 represents the longest follow-up for CIK to date and confirms the durable antitumor activity and tolerability of CIK cells therapy in combination with Sintilimab plus chemotherapy in advanced NCSLC. Further studies are warranted to confirm these preliminary results. Clinical trial information: NCT03987867 .
Safety and efficacy of inetetamab in combination with pyrotinib in HER2 mutant patients with non-small cell lung cancer (NSCLC): An open-label, phase Ib trial.
Authors: Fang Wenfeng , Zhao Yuanyuan , Huang Yan , Zhang Yaxiong , Hong Shaodong , Huang Yihua , Zhao Hongyun , Yang Yunpeng , Zhao Shen , Chen Gang , Zhou Huaqiang , Ma Yuxiang , Zhou Ningning , Zhang Li 
Published: June 2023

9105 Background: Currently, limited targeted therapies are available for HER2 mutant NSCLC patients. Previous studies have shown the antitumor activity of pyrotinib in advanced NSCLC patients with HER2 mutations. Inetetamab is a recombinant humanized anti-HER2 monoclonal antibody. Whether inetetamab combined with pyrotinib could show manageable safety and more active antitumor activity remains unknown. This study was designed to evaluate the safety and efficacy of inetetamab in combination with pyrotinib in HER2 mutant patients with advanced NSCLC. Methods: This study was an open-label, phase Ib study. The HER2 mutant patients with locally advanced or metastatic NSCLC were assigned to receive inetetamab combined with pyrotinib. The study consisted of dose-escalation part and dose-expansion part. During dose-escalation period, the parallel "3+3" dose-escalation design was used to determine the dose-limiting toxicity (DLT). Inetetamab was administered every 3 weeks (8 mg/kg loading dose for cycle 1, followed by 6 mg/kg in subsequent cycles) with pyrotinib (dose-escalation part, 240mg QD, 320mg QD; dose-expansion part, 320mg QD). Primary endpoint of the study was DLT dosage and safety. The DLT was assessed during the 21-day DLT evaluation period after the first dose. Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression free survival and overall survival. Results: Between August 6, 2021, and August 25, 2022, 48 patients were enrolled. No DLT occurred during pyrotinib 240mg and 320mg escalation period. Therefore, pyrotinib 320mg was chosen as expansion dose. The most common treatment-related adverse events (TRAEs) were diarrhea (66.7% [2/3] in pyrotinib 240mg group, 95.6% [43/45] in pyrotinib 320mg group), rash (66.7% [2/3] in pyrotinib 240mg group, 22.2% [10/45] in pyrotinib 320mg group) and vomiting (0 in pyrotinib 240mg group, 24.4% [11/45] in pyrotinib 320mg group). TRAEs were generally Grade (G) 1-2. Only 7 patients reported G3 TRAE (1 in pyrotinib 240mg group, 6 in pyrotinib 320mg group). The preliminary efficacy was shown in the table below. The ORR and DCR of group receiving inetetamab with pyrotinib 240mg were 0% and 66.7%, respectively. The ORR and DCR of inetetamab with pyrotinib 320mg group were 36.6% and 85.4% respectively. The relationship between different mutation subtypes or co-mutations and efficacy will be updated during the conference reports. Conclusions: The preliminary data of inetetamab in combination with pyrotinib showed manageable safety and compelling antitumor activity in advanced NSCLC patients harboring HER2 mutations. Clinical trial information: NCT05016544 . [Table: see text]
Amivantamab and lazertinib in treatment-naïve EGFR-mutated advanced non–small-cell lung cancer (NSCLC): Long-term follow-up and ctDNA results from CHRYSALIS.
Authors: Lee Se-Hoon , Cho Byoung Chul , Han Ji-Youn , Cho Eun Kyung , Lee Jong-Seok , Lee Ki Hyeong , Curtin Joshua C , Gao Grace , Xie John , Schnepp Robert W. , Bauml Joshua Michael , Knoblauch Roland E. , Thayu Meena , Kim Dong-Wan 
Published: June 2023

9134 Background: CHRYSALIS (NCT02609776) evaluated the combination of amivantamab (ami) and lazertinib (laz) in treatment-naïve patients (pts) with epidermal growth factor receptor ( EGFR)-mutated NSCLC. As previously reported, all 20 pts achieved a partial response (overall response rate of 100%) but interpretation of long-term outcomes was limited by the length of follow up (Cho Ann Oncol 2020;31:suppl_4, 1258O; Cho J Thorac Oncol 2022;17:S126, P1.16-01). Herein, we present long-term results from this treatment-naïve cohort. Methods: The treatment-naive cohort enrolled pts with EGFR exon 19 deletion (ex19del) or L858R mutated advanced NSCLC. All pts received 1050 mg IV ami (1400 mg if ≥80 kg) and 240 mg oral laz. Response was assessed by the investigator per RECIST v1.1. Circulating tumor DNA (ctDNA) was analyzed from plasma samples prior to initiation of treatment, at Cycle 3 Day 1, and at end of treatment (EOT). Results: Of the 20 pts enrolled in the treatment-naive cohort (median 62.5 years, 55% women, all Asian), 11 had EGFR ex19del and 9 had L858R NSCLC. As of Nov 15, 2022, the median follow-up and duration of treatment were 33.6 and 33.5 months, respectively. Ten (50%) pts were progression-free and remained on treatment, including 7 of 11 (64%) with ex19del and 3 of 9 (33%) with L858R. The median duration of response (DOR), median progression-free survival (PFS), and median overall survival (OS) were not estimable. The estimated landmark PFS rate was 85% at 12 months, 65% at 24 months, and 51% at 36 months. Of note, 2 (10%) pts were treated beyond progression. The longest ongoing pt has a duration of treatment of 37.2 months and DOR of 35.7 months. Treatment-related dose interruptions, reductions, and discontinuations of either ami and laz occurred in 7 (35%) pts, 8 (40%) pts, and 1 (5%) pt, respectively. The safety profile was consistent with prior reports, with predominantly on-target EGFR- or MET-related adverse events. Among the 10 pts who discontinued treatment, 4 submitted samples for ctDNA analysis at both baseline and EOT. There was 1 pt with new PIK3CA mutations, 1 with low-level HER2 amplification, 1 pt with a new CCNE1 and EGFR amplification, and 1 pt with no new mutations detected. Updated data on ctDNA at EOT may be available at the time of congress presentation. Conclusions: At a median duration of treatment of 33.5 months, median DOR, PFS, and OS have not been reached in treatment-naïve pts receiving ami+laz, with 50% remaining progression-free and on treatment. No new safety signals were identified. The ongoing phase 3 MARIPOSA study (NCT04487080) is further investigating ami+laz vs osimertinib vs laz in previously untreated, EGFR-mutated, advanced NSCLC. Clinical trial information: NCT02609776 .
Role of nivolumab maintenance therapy in advanced melanoma patients following severe immune-related adverse events from combination nivolumab and ipilimumab.
Authors: Maloney Anna , Giobbie-Hurder Anita , Fogarasi Miklos C. , Ott Patrick Alexander , Hodi F. Stephen , Sussman Tamara A. , Silk Ann W. , Haq Rizwan , Liu David , Insco Megan Leigh , Buchbinder Elizabeth Iannotti 
Published: June 2023

9520 Background: The combination of ipilimumab (ipi), and nivolumab (nivo) has been shown to be a highly effective treatment for metastatic melanoma. However, immune-related adverse events (irAEs) are common with this treatment, leading to treatment interruption and the use of immunosuppressive agents. There are no data on the impact of resuming single agent nivo on survival outcomes following recovery from the irAE and completion of immunosuppressive treatment. Some physicians hold therapy permanently as done on clinical trials and other physicians resume nivo after steroid taper. Methods: In this retrospective analysis, we examined a cohort of patients treated with ipi/nivo who developed irAEs that required treatment interruption and immunosuppressive therapy. The differences in practice patterns among physicians at our institution allowed us to examine the effect of single agent nivo resumption on survival after treatment of irAEs. Multivariate analysis of clinical factors associated with improved survival was performed. Results: We identified 165 patients who were treated with ipi/nivo and developed irAEs requiring treatment interruption and immunosuppressive therapy. To remove any impact of immediate disease progression on the analysis patients who progressed on ipi/nivo prior to or during treatment hold were removed from analysis. Of the remaining 131 patients, 45 resumed single agent maintenance nivo following the resolution of toxicity and completion of steroid taper. When stratified by age and adjusted for sex, M-stage, LDH, duration of therapy, and type of irAE causing the treatment pause, the effect of resumption of nivo upon survival remained highly significant (p = 0.001). Patients who resumed nivo had an 82% reduction in the hazard of death compared with patients who had not yet or never resumed nivo (HR: 0.18, 95% CI: 0.06 to 0.52). Of the patients who resumed nivo, 12 (26%) patients had subsequent irAEs with 5 patients having grade 3 irAEs (only one of whom had a recurrence of the prior ipi/nivo associated toxicity) and no grade 4 or 5 irAEs were noted. Conclusions: The resumption of single agent maintenance nivolumab following a treatment hold for ipi/nivo associated irAE and completion of immunosuppressive therapy increased overall survival compared to discontinuing nivo permanently in patients with metastatic melanoma after stratification for many factors. Toxicity observed post resumption of single agent nivolumab was manageable with no severe irAEs observed. These results suggest that restarting maintenance nivo post irAEs should be studied prospectively.
Real-world treatment patterns and clinical outcomes among subgroups of BRAF-positive metastatic melanoma patients treated with dabrafenib + trametinib.
Authors: Eroglu Zeynep , Tang Jackson , Byrne Clare , Connolly Lucy , Shah Rohan , Truong Thach-Giao 
Published: June 2023

9521 Background: Whether disease attributes such as tumor burden or central nervous system (CNS) metastases can affect outcomes for patients with BRAF+ metastatic melanoma (MM) is currently unclear. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes among subgroups of patients with BRAF+ MM treated with dabrafenib + trametinib (dab/tram) in the United States. Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived de-identified database from 1/1/2014 to 9/30/2021. Included patients were aged ≥18 years with a diagnosis of BRAF+ MM and received first-line (1L) dab/tram. Patients were stratified into 4 subgroups: high tumor burden (HTB; ≥3 sites of metastasis and lactate dehydrogenase [LDH] ≥333 IU/L), low tumor burden (LTB; <3 sites of metastasis and LDH <333 IU/L), with CNS metastases (prior to 1L dab/tram), and without CNS metastases (prior to 1L dab/tram). Patient characteristics and treatment patterns were evaluated descriptively. Given the potential patient overlap between subgroups, no comparative statistics were conducted. Real-world progression-free (rwPFS) and overall survival (OS) were explored from dab/tram initiation. Results: Among 460 included patients (mean age 60 years, 64% male), 66 (14%) had a HTB, 69 (15%) had a LTB, 164 (36%) had CNS metastases, and 296 (64%) did not. Patient characteristics were comparable across the subgroups. Over 60% of HTB patients had documented metastases in each of the liver, lung, bone, lymph nodes, and other sites. Only lung metastases had >60% prevalence among patients with a LTB. Overall, 51% of the included patients went on to receive a second-line therapy; LTB patients and those without CNS metastases had a longer time to next therapy. The median rwPFS and OS were significantly shorter among patients with a HTB vs LTB, and among patients with vs without CNS metastases (Table). Conclusions: Both tumor burden and presence of CNS metastases appear to have a significant impact on survival among BRAF+ MM patients treated with 1L dab/tram. With growing use of 1L immunotherapy in MM, 1L BRAF/MEK inhibitors are increasingly being used in patients with a worse prognosis, which may explain the lower rwPFS and OS with dab/tram when compared with clinical trials. [Table: see text]