bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of vorolanib in combination with toripalimab in patients with non-small cell lung cancer.
Authors: Zhao Jun , Li Jianjie , Chen Hanxiao , Yang Xue , Zhong Jia , Zhuo Minglei , Jia Bo , An Tongtong , Wu Meina , Wang Ziping , Ding Lieming , Mao Li 
Published: June 2021

e21053 Background: VEGF promotes an immunosuppressive microenvironment and contributes to resistance of immune checkpoint inhibitors in cancer treatment. VEGF inhibitors have been shown to enhance efficacy of checkpoint inhibitors in clinical studies. Vorolanib (CM082) is a multi-target tyrosine kinase inhibitor including VEGF, PDGF, c-kit, and Flt-3. Toripalimab (JS001) is a humanized IgG4 mAb against programmed death-1 (PD-1). This phase II study aims to evaluate efficacy and safety of the combination of vorolanib and JS001 in non-small cell lung cancer (NSCLC) patients who progressed with prior first-line standard therapy. Methods: This single-arm, single-center, phase II study (NCT03848611) enrolls NSCLC patients with measurable disease (RECIST 1.1) and Eastern Cooperative Oncology Group performance status ≤ 1, regardless of PD-L1 status. 15 patients received 150 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks while 3 patients received 100 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR). Results: Between April 2019 and July 2020, 18 patients were enrolled. Median age was 64 years. 9 of 18 patients (50%) were adenocarcinoma and 9 of 18 patients (50%) were squamous. Males account for 83% (15/18) with 4 non-smokers among the male patients. At the data cutoff (January 11, 2021), we observed 2 (11%) confirmed and 1 (6%) unconfirmed partial response (PR), 6 (33%) stable disease (SD) and 9 (50%, including 2 PR of the target lesions) progression disease (PD). Tumor shrinkage was seen in 6 (33%) of the 18 patients. Two (11%) patients were still on the study drugs. Interestingly, all the patients with confirmed PR or PR of the target lesions were squamous histology. The most common treatment-related adverse events were proteinuria (67%), elevated ALT (60%), elevated AST (53%), hypertension (40%), and increased bilirubin (40%). Grade 3 adverse events include elevated ALT (20%), elevated AST (20%), liver function damage (13%), elevated GGT (7%), fatigue (7%), bellyache (7%), ruptured and infected tumor (7%), and dysphagia (7%). One Grade 4 adverse event was pulmonary embolism. Conclusions: Vorolanib with toripalimab showed a promising antitumor activity with acceptable safety profiles for patients with NSCLC. We hypothesized that the potential benefits of combination therapy for patients with squamous cell carcinoma may be better than those for patients with adenocarcinoma, and the study is ongoing. Clinical trial information: NCT03848611.
A phase I/II study of TQ-B2450, a PD-L1 mAb, plus anlotinib in EGFR+ advanced NSCLC patients failed to prior EGFR TKI therapies.
Authors: Shi Meiqi , Wang Li , Yu Shaorong , Yan Fei , Peng Wei , Feng Jifeng 
Published: June 2021

e21062 Background: Platinum-based chemotherapy is the standard therapy for the patients(pts) with EGFR-mutation–positive advanced NSCLC failed to prior EGFR TKI therapies. However, the IMpower150 study subgroup analyses showed Atezolizumab (PD-L1) plus bevacizumab and chemotherapy improved overall survival in EGFR TKI treated NSCLC. This ongoing phase I/II study designed to assess the benefit of the chemo-free combination of TQ-B2450, a humanized PD-L1 mAb, plus anlotinib in EGFR+ advanced NSCLC pts failed to prior EGFR TKI therapies. Methods: Pts with EGFR+ advanced NSCLC who failed to prior EGFR TKI therapies were eligible. Pts with previous received platinum-based chemotherapy were excluded. Anlotinib was given orally at dose of 8mg to 12mg for 2 weeks of a 21-day cycle (days 1-14), with TQ-B2450 given at 1200mg every 3 weeks on day 1. Phase I determined RP2D. In the phase II part, pts were assessed for efficacy and tolerability. The primary endpoint for the phase II part is the progression free survival (PFS). Secondary endpoints were objective response rate (ORR) disease control rate (DCR), overall survival (OS), and safety. Assuming an expected the median PFS of 9 months (5 months in chemotherapy), and a loss to follow-up of 10%, a total of 54 pts were required to have 90% power at a two-tailed alpha of 0.05 at the phase II part. Results: As of 12 Jan 2021, 22 pts were enrolled (9 in phase 1, 14 in phase 2). 18 pts were included in efficacy and safety analysis. The median age was 64.5 years with 61% male. 50% pts harbored EGFR exon19 deletion, 44% pts had exon21 L858R mutation. While 39% pts had T790M mutation who progressed after osimertinib treatment. The dose escalation cohort included 9 pts, no dose limiting toxicity occurred. 13 pts in the phase II part were administered with dose of 12 mg for anolitinib and 1200mg for TQ-B2450. Of the evaluable pts(n = 18), ORR was 11.1%, DCR was 77.8%, median PFS was 8.0 months (95% CI 4.9 to 11.1). Most frequent TRAE included hypertension (27.8%), hand and foot skin reaction (22.2%) and proteinuria (16.7%). Grade 3 TRAE occurred in 16.7% pts(3/18 pts), all were hypertension, and no Grade 4/5 TRAE were observed. Dose delay due to TRAE occurred in 22.2% patients while no one discontinued treatment due to TRAE. Conclusions: The chemo-free combination of TQ-B2450, a PD-L1 mAb, plus anlotinib has shown a promising anti-tumor efficacy with a more favorable safety profile for pts with EGFR+ advanced NSCLC who failed to prior EGFR TKI therapies. Pts will be continuously monitored for safety and efficacy readouts (PFS, DOR and OS). Clinical trial information: ChiCTR1900026273. Clinical trial information: ChiCTR1900026273.
Efficacy and safety of low-dose albumin-bound paclitaxel plus tislelizumab as second- or further lines treatment for elderly patients with metastatic non-small cell lung cancer.
Authors: Geng Qian , Li Dongqing , Zhu Wenyu , Peng Haoliang , Jin Zhihui , Jiang Hua 
Published: June 2021

e21066 Background: Lung cancer ranks first globally in morbidity and mortality rates among cancers. There are few studies focused on the different doses of chemotherapy drugs in combination with programmed cell death-1 (PD-1) inhibitors in non-small-cell lung cancer (NSCLC). Tislelizumab, a novel PD-1 monoclonal antibody, has been shown to improve antitumor activity when combined with chemotherapy as first-line treatment for patients with NSCLC. Elderly patients usually have poor physical conditions and many complications, resulted in higher risks of chemotherapy. This study aimed to preliminarily assess the efficacy and safety of low-dose chemotherapy plus tislelizumab for elderly patients with metastatic NSCLC. Methods: Eligible patients should be diagnosed as metastatic NSCLC, aged ≥65 years, and failed in one or more lines treatment. Patients with epidermal growth factor receptor (EGFR) / anaplastic lymphoma kinase (ALK) inhibitor resistance could be enrolled in the study. Participants received albumin-bound paclitaxel (130mg/m2) plus tislelizumab (200mg) every 3 weeks. Chemotherapy lasted for no more than 6 cycles. Once chemotherapy intolerance occurred or at end of 6 cycles, patients with objective response or stable disease would continue to receive tislelizumab until confirmed disease progression, death, and unacceptable toxicity. Primary endpoints were progression free survival (PFS) and safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), as well as overall survival (OS). Results: Total 23 patients were enrolled from May 2019 to March 2020: 43.5% (10/23) male, 39.1% (9/23) smokers, 26.1% (6/23) with squamous cell carcinoma and 56.5% (13/23) with ECOG 2. Median age was 71 yr (range: 65, 82). Patients had received 1 (47.8%) or ≥2 (52.2%) lines of therapy. 13 (56.5%) patients with EGFR/ALK TKI resistance participated in the study. As of data cut-off on December 1, 2020, the median PFS was 9.5 months (95% CI: 5.7–13.3 months). Nine patients achieved partial response (PR). The ORR was 39.1% (9/23) and DCR was 87.0% (20/23). Only 4 participants died in the study and the mOS was not reached. Sixteen (69.6%) patients had a decrease in tumor size as compared with baseline and the median change from baseline was −22%. 13 (56.5%) participants suffered at least one adverse event (grade 3 in 3 (13.0%) patients). The main adverse events were fatigue (17.4%), fever (17.4%), abnormal liver function (17.4%), rash (13.0%) and numbness (13.0%). No grade 4 adverse event was reported. Conclusions: Low-dose albumin-bound paclitaxel plus tislelizumab might be an optional choice for elderly patients with metastatic NSCLC after the failure of platinum-based chemotherapy or targeted therapy. Perspective clinical studies with large sample size are needed to validate our results.
Progression pattern and post-progression treatment of furmonertinib (AST2818) in EGFR T790M mutation positive NSCLC patients: A post-hoc analysis from a multicenter, single-arm study.
Authors: Hu Xingsheng , Zhang Shucai , Lv Dongqing , Wu Lin , Yu Qitao , Zhang Yiping , Liu Li , Wang Xiang , Cheng Ying , Ma Zhiyong , Niu Hongrui , Wang Dong , Feng Jifeng , Huang Cheng , Liu Chunling , Zhao Hui , Li Jingzhang , Zhang Xiaodong , Jiang Yong , Shi Yuankai 
Published: June 2021

e21071 Background: Furmonertinib (AST2818) is a selective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which can irreversibly inhibit both EGFR sensitizing and T790M resistant mutations. However, like other EGFR-TKIs, progression is still unavoidable when treated with furmonertinib. Methods: In a multi-center, single-arm phase IIb study (NCT03452592), non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation received furmonertinib 80mg/d treatment until disease progression, death or treatment cessations for other reasons. This is a post-hoc analysis of the progression pattern and post-progression treatment. Results: A total of 220 patients were enrolled in this study. At baseline, 105 (48%) patients had central nervous system (CNS) metastases, 84 (38%) were EGFR L858R mutated and 9 (4%) were ECOG performance status 2. At data cut-off (December 31, 2020), 179 out of 220 (81%) patients had progressed assessed by investigators (patients who died before assessed as progression were excluded). The most frequent progression site was lung (n = 106，48%), followed by CNS (n = 33, 15%), lymph node (n = 22, 10%), liver (n = 20, 9%) and bone (n = 16, 7%). CNS progression rate were 3%, 8%, 13% and 15% at 3, 6, 12 and 18 months, respectively. After progression, 52% (93/179) patients continued furmonertinib monotherapy based on the judgement of continuous benefit by investigators which was permitted in the protocol. The median post-progression treatment time of furmonertinib was 3.02 months (range 0.03-18.27). Overall, 48% (86/179) patients discontinued furmonertinib and later-line treatments were decided by investigators. The post-progression survival (PPS) was 17.3 months in the furmonertinib-continued group and 12.4 months in the furmonertinib-not-continued group (HR 0.57 [95%CI 0.40-0.80], p = 0.0048). Conclusions: Although about half patients had CNS metastases at baseline, CNS progression rate was relatively low in this study. Post-progression continuous treatment of furmonertinib monotherapy might still bring survival benefit to certain NSCLC patients with EGFR T790M mutation which need further exploration. Clinical trial information: NCT03452592.
Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small cell lung cancer: A prospective and multicenter phase 2 trial.
Authors: Lv Weize , Zhong Beilong , Zhao Wenhua , Lin Zhong , Pei Xiaofeng , Wang Zhihui 
Published: June 2021

e21079 Background: Although the administration of immune checkpoint inhibitors (ICIs) and antiangiogenic agents in advanced non–small-cell lung cancer (NSCLC) has been well established, evidence supporting the combination of immune checkpoint inhibitors plus antiangiogenic drugs in previous treatment patients with advanced NSCLC is insufficient. We aimed to investigate the efficacy and safety of nivolumab combined with recombinant human endostatin (rh-Endostatin) as second-line or later treatment for advanced NSCLC. Methods: In this prospective and multicentre phase 2 trial we enrolled patients with advanced NSCLC who had not responded to standardized first-line treatment regimen from two cancer centres in China. Eligible patients were those aged 18-75 years without ICIs in first-line treatment who received nivolumab (3mg/kg, intravenous drip, day 1) every 2 weeks and rh-Endostatin (30 mg, 24-hour continous intravenous infusion，day 1–7) every 4 weeks till disease progression or discontinuation. The primary end points were objective response rate and safety. This study is registered with Chinese Clinical Trial Registry, number ChiCTR1900023664. Results: A total of 35 patients (median age, 60 years; range, 37-72 years) received nivolumab and rh-Endostatin. Median previous treated line of eligible patients was 2 lines (range, 1-7 lines). Patients received a median of 2 cycles of therapy (range, 1-14 cycles). Eleven of 33 evaluable patients achieved confirmed partial response with an objective response rate of 33.3% (11/33, 95% confidence interval [CI]: 17.2% – 49.4%) and disease control rate of 60.6% (20/33,95%CI:43.9%–77.3%). Median follow-up was 8.2 months (range: 0.9 –17.1). Median progression-free survival was 7.1 months (95% CI: 1.2m–13.0m), median overall survival was not reached and the 6-month overall survival rate was 54.5% (95% CI:37.6%–71.4%). The predominant grade 1-2 adverse events were thyroiditis, arrhythmia, hypertension. The grade 3 treatment-related adverse events were pneumonitis (3/35, 8.6%), hypertension (1/35, 2.9%) and atrial fibrillation (1/35, 2.9%), respectively. No grade 4 or 5 treatment-related adverse events were observed. Conclusions: To the best of our knowledge, this is the first prospective study that assessed nivolumab combined with rh-Endostatin as second-line or later treatment in pretreated patients with advanced NSCLC. In view of its encouraging efficacy and safety profile, nivolumab plus rh-Endostatin represents a promising treatment regimen in this patient population. Clinical trial information: ChiCTR1900023664.
Efficacy of weekly paclitaxel-bevacizumab combination in advanced nonsquamous non-small cell lung cancer (NSCLC): AVATAX, a retrospective multicentric study.
Authors: Bilger Geoffroy , Toffart Anne-Claire , Darasson Marie , Duruisseaux Michaël , Ulmer Lucie , Wang Pascal , Giroux Leprieur Etienne , Girard Nicolas , Massiani Marie Ange , Bore Paul , Descourt Renaud , Pinsolle Julian , Valery Solene , Monnet Isabelle , Swalduz Aurélie , Tissot Claire , Fournel Pierre , Baranzelli Anne , Cortot Alexis , Decroisette Chantal 
Published: June 2021

e21086 Background: With the growing role of immunotherapy (ICI) as first-line setting for advanced NSCLC, strategies must be redefined after failure. The combination paclitaxel-bevacizumab showed in the ULTIMATE trial a significant superiority versus docetaxel as second or third-line treatment. Limited restropective studies has demonstrated unexpected efficacy of chemotherapy after prior progression on ICI. This combination could be use as salvage treatment following ICI. Methods: This multi-centric retrospective study identifies patients treated with the combination paclitaxel-bevacizumab in metastatic non-squamous NSCLC as second-line therapy or beyond. Main objectives were to describe safety and efficacy of this combination, with a special attention to the sub-group treated just after ICI. Results: From January 2010 to February 2020, 314 patients started the paclitaxel-bevacizumab combination : 55% male, with a median age of 60 years, 27% with a performance status ≥2, 45% with brain metastases. A majority of patients were treated in second (20%) and third-line (39%), and 28% were treated just after ICI failure (88/314). Objective response rate (ORR) was 40% and disease control rate was 77 %. Median progression-free survival (PFS) and overall survival (OS) were 5,7 months [IQ,3,2–9,6] and 10,8 months [IQ,5,3–19,6] respectively. All grades adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued a monotherapy alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compare to those not previously treated with ICI (ICI-) : 7,0 months [IQ,4,2–11,0] vs 5,2 months [IQ,2,9–8,8] p (log-rank) = 0,01. There was not statistically significant difference in term of OS between this two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment (ICI+) and performance status. Conclusions: This study confirms an acceptable toxicity profile associated with interesting efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non–squamous NSCLC patients, particularly after progression with ICI.
Population pharmacokinetics (Pop PK) of MYL-1402O (a proposed biosimilar to bevacizumab) and reference product (Avastin) in patients with nonsquamous non-small cell lung cancer (nsNSCLC).
Authors: Owen Joel , Rackley Russell J. , Hummel Matthew A. , Roepcke Stefan , Huang Hannah , Liu Mark S. , Idris Tazeen A. , Nainar Murugesan Sundara Moorthi , Vishweswaramurthy Ashwini , Loganathan Subramanian , Ranganna Gopinath , Barve Abhijit J. , Waller Cornelius , Socinski Mark A. 
Published: June 2021

e21087 Background: MYL-1402O (MYL) is a proposed biosimilar to bevacizumab reference product. A multicenter, double blind randomized, phase 3 study compared the efficacy, safety, PK, and immunogenicity of MYL and Avastin in patients with Stage IV metastatic nsNSCLC. Patients received either MYL or reference product, in combination with carboplatin-paclitaxel up to 18 weeks (6 cycles) followed by monotherapy for up to an additional 24 weeks (8 cycles). The objective was to develop a Pop PK model based on data from a phase 3 study pooled with a single dose healthy volunteer phase 1 study data; to assess PK linearity across the dose levels of 1 mg/kg to 15 mg/kg in 2 clinical studies; to assess the PK similarity of MYL and reference product in patients with nsNSCLC; and to explore potential covariates to account for variability in Pop PK model parameters. Methods: A Pop PK model was developed based on preliminary analyses of MYL phase 1 data and published population analyses of reference product using a 2-compartment linear model (Han K et al., 2016). Individual empiric Bayesian parameter estimates of nsNSCLC patients were used to predict PK measures reflecting exposure to drug and were compared qualitatively between treatments. Results: The data subset used for model development consisted of 8724 records from 771 subjects. Population PK analyses indicated no differences between PK profiles of patients in the MYL and reference product arms. Importantly, treatment was not a significant covariate of clearance ( P = 0.453) or volume of the central compartment ( P = 0.161) using the likelihood ratio χ2 test. Model-based steady state exposure measures, predicted based on the final model for all patients, were also similar between treatment arms (Table). Conclusions: The model supported linear PK at clinical doses in patients with nsNSCLC; there were no clinically relevant/significant differences between the PK of MYL and reference product; and the findings were consistent with the PK study in normal, healthy volunteers. Bayesian Parameter Clinical trial information: 2015-005141-32. [Table: see text]
The very early tumor regression rate and safety of anlotinib combined with sintilimab and chemotherapy for advanced non-small cell lung cancer without driver mutations.
Authors: Jiang Jian , Jia Yuming , Ren Yue , Li Ting , Du Lei-Ya , Jiang Mao-Qiong , Qiu Ye , Chen Jie , Yan Jun , Li Li 
Published: June 2021

e21090 Background: Unlike bevacizumab, anlotinib, which is also an anti-angiogenic drug, is indicated for lung squamous cell carcinoma(LSCC). A phase IB study showed that the first-line therapy with anlotinib and sintilimab for stage IIIB to IV NSCLC with negative driver genes has the objective response rate of 72.7%. Regardless of the PD-1 expression level, this combination method has consistent therapeutic benefit. According to the IMpower150 study, the four-drug combination therapy has a synergistic effect and prolong the survival time. It is necessary to further explore the efficacy and safety of anlotinib combined with sintilimab and chemotherapy for NSCLC without driver mutations. Methods: We retrospectively analyzed the patients of newly diagnosed unresectable stage IIIA-IVB NSCLC who received platinum-containing dual-drug chemotherapy combined with anlotinib and sintilimab in our hospital from January 2019 to December 2020. Patients receive at least one cycle of treatment, and the efficacy can be evaluated. The main observation indicators are the very early tumor regression rate and the safety. Results: This study included 11 patients with stage IIIA-IVB NSCLC with no driver mutations that were not resectable. Ten patients (90.9%) were male, with a median age of 65 years. The pathological types were LSCC (7, 63.6%), lung adenocarcinoma (3, 27.3%), and poor differentiated carcinoma (1, 9.1%). Six patients were with stage ⅢA-ⅢB, 4 patient with ⅢC-IVB. Eleven patients received an average of 1.63 cycles of treatment. In order to evaluate the efficacy of multi-drug combination therapy in a timely manner, and effectively avoid the risk of hemoptysis caused by anlotinib-induced pulmonary cavity, all patients were evaluated for efficacy after receiving one cycle of treatment. Eight patients achieved very early tumor regression (defined as tumor shrinkage ≥30% after receiving one cycle of treatment in the evaluation of efficacy), 2 patients achieved stable disease, and 1 patients achieved disease progression. The very early tumor regression rate was 72.7%. Three patients with locally advanced (ⅢA-ⅢB) NSCLC underwent radical R0 resection and the downstage rate reached 100%; 2 patients underwent radical radiotherapy. At the last follow-up time in February 2021, one patient died, the remaining patients were alive. No treatment-related grade 3-4 adverse reactions were observed. Conclusions: The high rate of very early tumor regressions in inoperable locally advanced NSCLC provided opportunities for radical surgery and radiotherapy in a short period of time. And the safety is satisfactory. Therefore, our research group has registered the prospective study of anlotinib combined with sintilimab and chemotherapy for the neoadjuvant downstage treatment of stage III NSCLC (Registration number: ChiCTR1900026631).