bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEJ043: A phase 2 study of atezolizumab (atezo) plus bevacizumab (bev) plus carboplatin (carbo) plus paclitaxel (pac; ABCP) for previously treated patients with NSCLC harboring EGFR mutations (EGFRm).
Authors: Furuya Naoki , Watanabe Satoshi , Nakamura Atsushi , Shiihara Jun , Nakachi Ichiro , Tanaka Hisashi , Nakao Mika , Minato Koichi , Seike Masahiro , Sasaki Shinichi , Kisohara Akira , Takeuchi Susumu , Honda Ryoichi , Takamura Kei , Kagamu Hiroshi , Yoshimura Kenichi , Kikuchi Toshiaki , Kobayashi Kunihiko ,   North East Japan Study Group (NEJSG)
Published: June 2022

9110 Background: Previous studies have demonstrated poor clinical outcomes of patients (pts) with EGFRm NSCLC treated with PD-1/PD-L1 inhibitors. However, a recent subgroup analysis of the IMpower150 trial suggested the effectiveness of ABCP in NSCLC with EGFRm. The aim of this study is to further evaluate efficacy and safety of ABCP in patients with EGFRm NSCLC. Methods: This single-arm multicenter phase 2 study included pts with nonsquamous NSCLC harboring sensitizing EGFRm with prior EGFR-TKI therapy. Pts received the combination dose of atezo 1200 mg, bev 15 mg/kg, carbo AUC 6 mg/mL/min and pac 175 mg/m2 every 3 weeks up to 4 cycles followed by atezo plus bev until loss of clinical benefit. The primary endpoint was PFS by extramural review (ER). The key secondary endpoints included OS, ORR, DoR, relative dose intensity of pac, and safety. Results: 60 pts were enrolled (median age 68 y [40–74 y], 67% were female, 55% were Ex19del and 40% were L858R). At data cutoff (November 30, 2021), median follow-up was 12.8 months in the ITT population. Median cycles of induction and maintenance therapy were 4 and 9, respectively. Median PFS was 7.4 month (95% CI, 5.7-8.2) and median OS was 18.9 month (95% CI, 13-not reached). Confirmed ORR by ER was 56% (95% CI, 43-69) and median DoR was 7.1 months (95% CI, 4.9-9.8). T790M was associated with a favorable PFS and response to the combination therapy (PFS 8.1 vs 6.8, ORR 71% vs 50%). Relative dose intensity of pac was 84%. Grade ≥3 adverse events (AEs) were reported in 92% of pts and the most common grade ≥3 AE was neutropenia (63%). Interstitial lung disease occurred in one patient (2%). AEs leading to treatment discontinuation occurred in 12% of pts. Conclusions: NEJ043 study showed that the median PFS of ABCP was 7.4 months with good tolerability. We will continue to investigate the tail plateau phenomenon of PFS and OS to conclude the clinical efficacy. Clinical trial information: 031190066.
Efficacy and safety of capmatinib plus pembrolizumab in treatment (tx)-naïve patients with advanced non–small cell lung cancer (NSCLC) with high tumor PD-L1 expression: Results of a randomized, open-label, multicenter, phase 2 study.
Authors: Mok Tony S. K. , Cortinovis Diego Luigi , Majem Margarita , Johnson Melissa Lynne , Mardjuadi Feby Ingriani , Zhao Xuan , Siripurapu Sagar Vidya , Jiang Zhiqiang , Wolf Juergen 
Published: June 2022

9118 Background: Capmatinib is a selective MET inhibitor approved for patients (pts) with metastatic NSCLC harboring MET exon 14 skipping mutation. Pembrolizumab (pembro) is a programmed death protein-1 (PD-1) inhibitor approved as monotherapy for pts with advanced NSCLC expressing PD-ligand 1 (PD-L1). Preclinical studies have shown that capmatinib enhances T cell mediated antitumor response in mice treated with PD-1 inhibitors. Combining capmatinib with pembro may be beneficial in pts with advanced NSCLC expressing high tumor PD-L1. Methods: Herein we evaluated the efficacy and safety of capmatinib plus pembro (combo) versus pembro alone in tx-naïve pts with advanced MET-unselected NSCLC expressing PD-L1 with tumor proportion score (TPS) ≥50%, and no ALK or EGFR tumor aberrations. Pts received pembro 200 mg IV q3w in the pembro alone arm or with capmatinib 400 mg orally BID in the combo arm. The primary endpoint was investigator-assessed progression-free survival (PFS) using RECIST v1.1. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), pharmacokinetics and safety. Results: As of the data cut off (DCO) of 28 Feb 2021, 76 pts were randomized 2:1 to the combo arm (n = 51) or pembro alone arm (n = 25). Baseline demographics and disease status were mostly comparable across study arms. At this interim analysis, PFS data were not mature. Median PFS (95% CI) was 6.3 (3.2, not evaluable [NE]) months in the combo arm and 4.3 (2.3, NE) months in the pembro alone arm. The ORR (95% CI) was 15.7% (7.0%, 28.6%) and 28.0% (12.1%, 49.4%) in the combo and pembro alone arms, respectively. The DCR (95% CI) was comparable across study arms; combo: 56.9% (42.2%, 70.7%) and pembro alone: 56.0% (34.9%, 75.6%). In the combo arm, capmatinib exposure (Cmax: 3580 ng/mL [n = 7] and AUCtau: 19700 hr*ng/mL [n = 2]) was consistent with data from previous studies. Tx-related grade (GR) ≥3 adverse events (AEs) were more common in the combo (37.3%) vs pembro alone arm (16%). Tx-related AEs occurring in ≥10% of pts are shown in the Table. Tx discontinuation and dose adjustment/interruptions were more common in the combo (27.5% and 52.9%) vs pembro alone arm (16% and 16%). Capmatinib was stopped prematurely in the combo arm, and at DCO, 32 (62.7%) pts in the combo arm and 18 (72%) pts in the pembro alone arm were receiving pembro monotherapy. Conclusions: Combination tx with capmatinib and pembro was not well tolerated and did not improve antitumor activity in tx-naïve pts with advanced NSCLC with PD-L1 TPS ≥50%. Clinical trial information: NCT04139317. [Table: see text]
Activating MET kinase domain mutations define a novel molecular subtype of non–small cell lung cancer that is clinically targetable with the MET inhibitor elzovantinib (TPX-0022).
Authors: Pecci Federica , Ricciuti Biagio , Alessi Joao Victor Machado , Barrichello Adriana Paula de Castro , Vaz Victor R. , Lamberti Giuseppe , Lee Jessica Kim , Schrock Alexa Betzig , Goel Vikas K , Zimmerman Zach , Bahcall Magda , Janne Pasi A. , Awad Mark M. 
Published: June 2022

9124 Background: In non-small cell lung cancer (NSCLC), MET exon 14 skipping (METex14) mutations and MET amplification can be targeted with MET inhibitors. Here, we describe a novel, actionable molecular subtype of NSCLC characterized by activating MET-tyrosine kinase domain (MET-TKD) mutations in the absence of METex14 mutations. Methods: Clinicopathologic and genomic data were abstracted from NSCLC cases included in a multi-institutional cohort of tumors that underwent genomic profiling in the GENIE v10, China PanCancer, and the International Cancer Genome Consortium/ The Cancer Genome Atlas (ICGC/TCGA) datasets. External validation of the prevalence of MET-TKD mutations was performed on an independent cohort of NSCLC tissue and liquid samples from the Foundation Medicine genomic database. Results: Among 14,099 NSCLC samples in the multi-institutional cohort, 71 (0.5%) harbored MET-TKD mutations without concurrent METex14 mutations: 55 of these had uncertain pathogenic significance and 16 had known oncogenic potential, including MET H1094Y/R, D1228H/N/V, N1100S, H1106D, V1188I, and M1250T, in order of decreasing prevalence. In a separate cohort of 91,515 NSCLC samples from the Foundation Medicine database, MET-TKD mutations lacking concurrent METex14 mutations were identified in 799 (0.9%) samples, including H1094Y, L1195V, D1228H/N, M1250T and others. Among 60 NSCLC samples harboring MET-TKD mutations without concurrent METex14 mutations with complete genomic data in the multi-institutional cohort, 36 (60%) had concurrent driver alterations in KRAS, EGFR, ROS1, BRAF, HER2, or RET, while 24 (40%) had no concurrent oncogenic drivers. Among patients with available demographic data in the multi-institutional cohort, those with MET-TKD-mutant NSCLC (N = 70) were significantly younger than patients with METex14-mutant NSCLC (N = 353) (median age 63 [range 30-86] vs 73 [range 44-88], p < 0.0001), and there was no significant difference in sex or self-reported race. Confirmed partial responses to the MET tyrosine kinase inhibitor elzovantinib (TPX-0022) were observed in two patients with MET-TKD-mutant NSCLC and no other detectable driver mutations: a 64-year-old man with MET H1094Y-mutant NSCLC, and an 80-year-old man with MET F1200I-mutant NSCLC. Conclusions: Potentially actionable MET-TKD mutations lacking concurrent METex14 mutations represent a novel genomic subtype in 0.5-0.9% of NSCLC, and occur in the absence of other known drivers in a subset of cases.
Clinical and economic outcomes associated with upfront comprehensive genomic profiling in newly diagnosed advanced lung cancer in the United States from 2018-2020: Evidence from the SEQUENCE study.
Authors: Adeboyeje Gboyega , Caplan Eleanor , Xu Yihua , Chase Monica , Myer Nicole , Sheth Sheetal , Suehs Brandon T 
Published: June 2022

9126 Background: As the number of approved molecularly-targeted therapies for the treatment of lung cancer increases, the debate continues as to whether a clinical strategy leveraging next-generation sequencing (NGS) comprehensive genomic profiling (CGP) to match patients to targeted treatments is advantageous versus a narrow/single-gene (N/S) panel testing. We examined clinical and economic outcomes of patients with advanced lung cancer (aLC) in the United States (US). Methods: In this retrospective study, newly diagnosed aLC patients aged 65-89 years were identified from a US Medicare Advantage plan from 2018-2020. Patients receiving genomic testing within 90 days of diagnosis and an FDA-approved pharmacotherapy cancer treatment after diagnosis were categorized by initial sequencing with NGS CGP (51+ genes) vs N/S (≤50 genes) panel testing using administrative claims based on previously validated algorithms. We assessed the proportion of patients with an inpatient or emergency department (INP/ED) visit for select outcomes (e.g., neutropenia) within 6 months of start of treatment, all-cause mortality, and PPPM (per patient per month) total healthcare costs through all available follow-up. Genomic testing costs within 90 days of cancer diagnosis were estimated using the Medicare fee schedule. Among patients with treatment within 30 days of testing, we assessed the proportion who did not switch treatment and were alive within 6 months. Descriptive analyses were conducted, and average effects were estimated using inverse probability weighted regression models. Results: We identified 3,532 patients who received genomic testing and pharmacotherapy cancer treatment (NGS CGP, n = 968; N/S, n = 2,564). Characteristics were similar between testing groups. The proportion of patients with INP/ED for outcomes of interest was similar following NGS CGP vs. N/S panels (15.0% vs. 17.8%; IRR [95% CI]: 0.76 [0.57 – 1.02]; p = 0.066), as were mortality (56.2% vs. 59.2%; HR: 1.05 [0.95 - 1.16]; p = 0.323) and PPPM costs (PPPM median cost difference -$575; ratio from regression 0.99, 0.94-1.04; p = 0.228). Among a subgroup of patients treated within 30 days of testing, a higher proportion receiving NGS CGP did not switch treatment and were alive after 6 months (47.6%) vs those receiving N/S panels (39.8%) (OR [95% CI]: 1.33 [1.12 - 1.59]; p = 0.001). Median genomic testing costs were $3,049 for NGS CGP vs. $218 for N/S testing. Conclusions: Outcomes were similar between patients receiving NGS CGP and N/S panel testing. Among patients with treatment within 30 days of testing, upfront NGS CGP was associated with fewer patients switching treatment and 6-month survival. Upfront testing with NGS CGP may represent a beneficial genomic profiling strategy as part of the initial management of patients with aLC.
Molecular testing and patterns of treatment in patients with NSCLC: An IASLC analysis of ASCO CancerLinQ Discovery Data.
Authors: Behera Madhusmita , Joseph Gregory , Rupji Manali , Huang Zhonglu , Bunn Becky , Wynes Murry , Switchenko Jeffrey M. , Scagliotti Giorgio V. , Higgins Kristin Ann , Tsao Ming Sound , Belani Chandra Prakash , Sequist Lecia V. , Ramalingam Suresh S. 
Published: June 2022

9128 Background: Precision medicine has resulted in improved outcomes for non-small cell lung cancer (NSCLC); while molecular testing is considered critical for guiding treatment decisions for advanced stage NSCLC, adoption of testing in routine practice is variable. We analyzed the factors contributing to molecular testing and treatment patterns in patients with lung cancer. Methods: The ASCO CancerLinQ Discovery dataset was queried to identify patients diagnosed with lung cancer between the years 2010-2018. Data on demographics, tumor stage, histology and treatments were extracted, and receipt of molecular testing was investigated as the primary outcome. Univariate association of each clinicopathological variable with molecular testing outcome was performed using chi-square test for categorical variables and ANOVA test for numerical variables. A multivariable logistic regression analysis with backward selection at an alpha of 0.05 was reported. All analyses were conducted using SAS 9.4. Results: A total of 37,925 NSCLC patients with stage IV disease were analyzed. Patient characteristics: median age 65 years, 51% male, 68% white, 33.5% adenocarcinoma. Approximately 22% of all NSCLC patients had molecular testing results. In adenocarcinoma patients, 49% had molecular testing results available. In the stage IV group, 47% were treated with chemotherapy, 16% with immunotherapy and 3% with targeted therapy. On multivariable analysis, females were more likely to have molecular testing compared to males [(OR: 1.29 (1.22-1.37); p < 0.001]. Compared to White patients, Black patients were less likely to have molecular testing [OR: 0.89 (0.81-0.97); p = 0.009] and Asians were more likely to undergo testing [OR: 2.22 (1.79-2.75); p < 0.001]. Hispanic patients were more likely to undergo molecular testing compared to non-Hispanics [OR:1.24 (1.02-1.52); p = 0.03]. Additionally, treatment with immunotherapy [OR: 1.86 (1.72-2.01); p < 0.001] and targeted therapy [OR: 2.29 (2.00-2.64); p < 0.001] were associated with significantly higher likelihood of having molecular testing. These results were also confirmed on a subgroup analysis of adenocarcinoma patients. Conclusions: In this analysis of a US-based real-world dataset of stage IV NSCLC patients, White race and female sex are associated with higher likelihood of having molecular test performed. The percentage of patients undergoing testing remains sub-optimal.
A phase II clinical trial of camrelizumab (CAM, an IgG4 antibody against PD-1) combined with apatinib (APA, a VEGFR-2 tyrosine kinase inhibitor) and temozolomide (TMZ) as the first-line treatment for patients (pts) with advanced acral melanoma (AM).
Authors: Si Lu , Li Caili , Bai Xue , Zhou Li , Mao Lili , Cui Chuanliang , Chi Zhihong , Sheng Xinan , Lian Bin , Wang Xuan , Tang Bixia , Yan Xieqiao , Li Siming , Kong Yan , Dai Jie , Wei Xiaoting , Li Juan , Yang Fan , Pang Zheng , Guo Jun 
Published: June 2022

9508 Background: PD-1 monotherapy as the first line stand treatment for advanced melanoma yields an objective response rate (ORR) of < 20% in AM. Although multiple clinical trials are ongoing testing TMZ/APA, TMZ/PD-1 and APA/PD-1 combo therapies in AM, the reported ORR (range 17-23.8%) are far from satisfactory. We therefore conducted a phase II study of CAM/APA/TMZ combo in this subtype aiming for improved efficacy. Methods: We performed a single center, single arm phase II study (NCT04397770) testing the efficacy and safety of CAM/APA/TMZ combo as first-line therapy in pts with advanced AM. The primary endpoint was ORR per RECIST1.1, secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. All pts received iv CAM (200mg q2w), iv TMZ (200mg/m2 d1-5, q4w) and po APA (250mg qd) until disease progression or intolerable toxicity. Results: By Jan 2022, fifty pts were enrolled (48 evaluable), the median follow-up was 12.1 mo (IQR 8.4-14.5). Thirty-one pts achieved CR/PR as the best response (including 1 CR and 30 PR), the ORR was 64.6% (95% CI 49.4-77.4%). The DCR was 95.8% (95%CI, 84.6-99.3%). Both the median PFS and OS was not reached (NR); 6-mo and 12-mo PFS rate was 81.7% (95%CI 71.6-93.3%) and 62.9% (95%CI 48.4-81.7%), respectively; 12-mo OS rate was 82.3% (95%CI 68.2-99.2%). The incidence of treatment-related adverse events (TRAEs) was 94% (47/50). Of 50 patients, the most common grade ≥3 TRAEs included γ-glutamyl transferase elevation (24.0%), direct bilirubin elevation (22.0%), aspartase transaminase elevation (20.0%), alanine transaminase elevation (16.0%), and hypertriglyceridemia (14.0%). No treatment-related deaths occurred. Conclusions: The CAM/APA/TMZ combination demonstrated promising efficacy as the first-line treatment for pts with advanced AM, and was generally well tolerated. Phase III randomized control trial is warranted. Clinical trial information: NCT04397770.
Long-term outcomes of a phase II trial of neoadjuvant immunotherapy for advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN).
Authors: Gross Neil D. , Ferrarotto Renata , Amit Moran , Nagarajan Priyadharsini , Yuan Ying , Bell Diana , Johnson Jason M. , Morrison William H. , Rosenthal David Ira , Glisson Bonnie S. , Johnson Faye M. , Mott Frank , Esmaeli Bita , Diaz Eduardo , Gidley Paul , Goepfert Ryan , Lewis Carol M. , Wargo Jennifer Ann , Weber Randal S. , Myers Jeffrey 
Published: June 2022

9519 Background: In a pilot phase II trial, we investigated the use of neoadjuvant immunotherapy to induce a pathologic response in patients with stage III/IV (M0) cutaneous squamous cell carcinoma of the head and neck (CSCC-HN). Here, we report the long-term outcomes according to pathologic response. Methods: Patients with newly diagnosed or recurrent stage III/IV (M0) (AJCC 8th Ed) CSCC-HN were treated with 2 doses of cemiplimab 350 mg intravenously every 3 weeks prior to surgery. The primary endpoint was overall response rate (ORR) per RECIST v1.1. Secondary endpoints included safety, pathologic response, disease-free and overall survival. Results: Of 20 patients enrolled, 7 (35%) had recurrent disease and 12 (60%) were stage IV on presentation. Neoadjuvant immunotherapy was generally well-tolerated and there were no surgical delays. Adverse events (AEs) were observed in 7 (35%) patients; 1 (5%) grade 3 diarrhea, 6 (30%) ≤ grade 2 AEs. ORR by RECIST was 30%. However, 85% (17/20) achieved a pathologic response (≤50% viable tumor), with pathologic complete response (pCR) in 11 (55%), major pathologic response (MPR, ≤10% viable tumor) in 4 (20%) and pathologic partial response (pPR, >10% and ≤50% viable tumor) in 2 (10%). Patients with a pCR did not receive planned radiotherapy after surgery. Patients who did not have a pathologic response (> 50% viable tumor) either progressed and died (1, 5%) or developed recurrence (2, 10%) despite surgery and adjuvant radiation or chemoradiation. At a median follow up of 34.5 months (range: 7.7-42.7), none of the patients who achieved a pathologic response have recurred. Conclusions: Consistent with other cancer types, pathologic response to neoadjuvant immunotherapy is durable in patients with advanced, resectable CSCC-HN. Adjuvant radiation therapy may be spared in patients who achieve a pCR and warrants further investigation. Clinical trial information: NCT03565783.
Efficacy and safety of cosibelimab, an anti–PD-L1 antibody, in patients with metastatic cutaneous squamous cell carcinoma.
Authors: Clingan Philip R. , Brungs Daniel , Arnold Susan , Coward Jermaine , Fourie Samuel J. , Harris Dean Laurence , Kurochkin Andrii , Ladwa Rahul , Malan Niel , Mant Andrew Michael , McGrath Margie , Sharma Vinay , Shue Hong , Tazbirkova Andrea , Oliviero James , Desai Jayesh 
Published: June 2022

9537 Background: Programmed death receptor-1 (PD-1)–blocking antibodies are approved as monotherapy treatment for patients (pts) with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or radiation. Cosibelimab is a high-affinity, fully human programmed death ligand-1 (PD-L1)–blocking antibody with a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against tumor cells. Study CK-301-101 (NCT03212404) is a global, multicenter, multicohort, pivotal trial that enrolled pts with select advanced cancers for treatment with cosibelimab. Here we present the primary analysis of the registration-enabling expansion cohort in pts with metastatic CSCC. Methods: Adult pts with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 who had metastatic (nodal and/or distant) CSCC not amenable to local therapy were eligible to participate. Cosibelimab was administered as a fixed dose of 800 mg every 2 weeks (Q2W) intravenously. The primary endpoint was confirmed objective response rate (ORR; complete response [CR] + partial response [PR]) assessed by independent central review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and the key secondary endpoint was duration of response. Results: Seventy-eight pts with metastatic CSCC were treated with cosibelimab and comprise the efficacy and safety populations (59M/19F; median age: 71 years). The confirmed ORR was 47.4% (95% CI: 36.0, 59.1; 6 CRs and 31 PRs) and the median duration of response was not reached at the time of data cutoff (median duration of follow-up: 15.2 months), with 76% of responses ongoing (range: 1.4-31.8+ months). The Kaplan–Meier estimated probability of maintaining a response at 6 and 24 months was 88.1% and 72.5%, respectively. Treatment-related adverse events (TRAEs) were reported in 54 pts (69.2%); 7 pts (9.0%) experienced at least 1 grade 3 TRAE (no grade 4 or grade 5 TRAEs were reported) with the most common being increased serum lipase in 2 pts. Conclusions: Treatment with cosibelimab monotherapy resulted in a robust ORR with durable responses and demonstrated a predictable and manageable safety profile in pts with metastatic CSCC, supporting its use in the treatment of this cancer. Clinical trial information: NCT03212404.