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Baohui Han
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FP07 - Pathology (ID 109)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP07.09 - Detection of Early Lung Cancer from Average-Risk Individuals and from Benign Nodule Carriers with a DNA Methylation Blood Test (ID 1845)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
Early detection is the key to reducing the death of lung cancer. An effective blood-based method for the early diagnosis of lung cancer has not yet been developed. Meanwhile, current strategies to differentiate benign and malignant lung nodules are also in lack of accuracy. Here we describe a blood test that can detect lung cancer early from average-risk individuals and from benign lung nodule carriers through assessment of a methylation panel of 8 genes in peripheral blood DNA.
Methods
Two independent retrospective studies were carried out to investigate the most distinguishable methylation loci among 38 candidate genes in peripheral blood DNA. All the blood was donated before surgery and before any cancer related treatment. The methylation levels of each CpG sites were semi-quantitatively measured by mass spectrometry.
Results
Out of the investigated 38 genes, 15 showed significant methylation difference between 161 lung cancer case (90.1% in Stage I) and matched 200 cancer free individuals in the discovery round. In the validation study, 8 genes had distinguishable methylation levels among 615 lung cancer case (92.2% in Stage I), 145 surgery confirmed benign lung nodule carriers, and 809 matched cancer free individuals. Taken together, for the average-risk individuals, when the specificity was 90%, the panel of 8 methylation genes had sensitivities around 70% for the detection of early stage lung cancer regardless of subtypes, stage and tumor size. Moreover, with the specificity of 90%, this panel had even higher sensitivities around 90% for the distinguishing benign lung nodule carriers from lung cancer, and this sensitivity was 83% for the very small nodules ≤1cm.
Conclusion
Together, these findings reveal in a large clinical cohort that the utility of DNA methylation markers in the peripheral blood for the effective early diagnosis of lung cancer even for the very small tumors ≤1cm.
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OA07 - Immuno-biology and Novel Immunotherapeutics from Bench to Bed (ID 228)
- Event: WCLC 2020
- Type: Oral
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 2
- Moderators:
- Coordinates: 1/30/2021, 10:30 - 11:30, Scientific Program Auditorium
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OA07.03 - Comutations in DDR Pathways Predict Atezolizumab Response in Non-Small Cell Lung Cancer Patients (ID 944)
10:30 - 11:30 | Author(s): Baohui Han
- Abstract
- Presentation
Introduction
Comutations in DNA damage response and repair (DDR) pathways have been reported to be potential predictors for immune checkpoint inhibitors (ICIs) treatment. However, this statement has not been confirmed yet. In this study, we aimed to explore the predictive value of comutations in DDR pathways using circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in non-small cell lung cancer (NSCLC) patients receiving atezolizumab or docetaxel.
Methods
Clinico-pathological data of NSCLC patients from POPLAR and OAK trials were collected. Blood-based FoundationOne NGS assay was used to determine genetic alterations and blood tumor mutational burden (bTMB). Nonsense mutations and splice site alterations of DDR genes were considered deleterious. The deleterious status of missense mutations was determined by manual review in COSMIC and OncoKB databases. Comutations (co-mut+) were defined as deleterious alterations in two or more DDR pathways or deleterious alteration(s) in one DDR pathway plus missense mutation(s) of unknown significance in other DDR pathways. Overall survival (OS), progression-free survival (PFS), and durable clinical benefit (DCB) were compared between co-mut+ patients than co-mut- patients receiving atezolizumab or docetaxel.
Results
A total of 853 NSCLC patients were included (n=429 for atezolizumab and n=424 for docetaxel) in this study. Of them, 49 patients (5.7%) were classified as co-mut+ in the whole cohort. The baseline characteristics were comparable between co-mut+ and co-mut- patients in terms of age, race, gender, histology, smoking status, lines of treatment, EOCG PS, and PD-L1 expression. Patients with co-mut+ had significantly longer sum of the diameters of tumor (P=0.006), number of metastatic site (P=0.026), and increased median bTMB (20 vs. 7 mutations/Mb, P<0.001) than those with co-mut-. A significantly higher DCB was observed in co-mut+ patients than co-mut- patients receiving atezolizumab (56.7% vs. 30.6%, P=0.003). Among co-mut+ patients, atezolizumab significantly improved median OS (15.5 months vs. 6.2 months; adjusted hazard ratio [HR] for death, 0.299; 95% CI, 0.154 to 0.578; P=0.008) and median PFS (6.9 months vs. 3.3 months; adjusted HR for disease progression or death, 0.395; 95% CI, 0.209 to 0.747; P=0.004) compared with docetaxel. Importantly, the interaction between co-mut+ and treatment was significant for OS (interaction P=0.014) and PFS (interaction P=0.010).
Conclusion
Comutations in DDR pathways were significantly associated with higher response rate to atezolizumab and improved survival in NSCLC patients. The presence of comutations in DDR pathways could help to identify patients who will benefit from ICIs therapy.
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OA07.09 - Sintilimab in Combination with Anlotinib as First-Line Therapy for Advanced NSCLC: Final Analysis of Primary Endpoints (ID 1480)
10:30 - 11:30 | Presenting Author(s): Baohui Han
- Abstract
- Presentation
Introduction
Evidence supporting the chemo-free combination of immune checkpoint inhibitors plus antiangiogenic TKIs in treatment naïve advanced NSCLC patients is insufficient. Our phase I study (NCT03628521) of sintilimab (anti-PD-1) combined with anlotinib (multi-target anti-angiogenesis TKI) had showed encouraging overall response as first line therapy for advanced NSCLC regardless of PD-L1 expressions. Here we present the updated efficacy and safety results and more sub-group analyses.
Methods
Eligible patients were treatment-naive, stage IIIB/IV NSCLC patients without EGFR/ALK/ROS1 mutations. Participants were given sintilimab (200mg IV day1 q3w) and anlotinib (12mg QD day1-14 q3w) till disease progression or unacceptable toxicity. The primary endpoints were ORR and safety, and the secondary endpoints included DCR, PFS and OS.
Results
From Sept. 2018 to Feb. 2019, 22 patients were enrolled and treated. As of Apr. 30th 2020, median follow-up was 15.8 months (range, 8.3-19.3), median treatment duration was 14.6 months (range, 3.7-19.3). In total, 16 patients achieved confirmed PR, ORR was 72.7% (49.8%, 89.3%) and DCR was 100% (84.6%, 100%). Patients with adenocarcinoma (n=9) seemed to have better response than squamous cell type (n=12, 88.9% vs 58.3%). The median TTR was 1.6 months (95% CI, 1.4, 2.9) and the median DOR was NR (95% CI: 3.2m, NC). The median PFS was 15 months (95% CI, 8.3 months-NR), and the 12-month PFS rate was 71.4% (95% CI, 47.2%, 86.0%). Patients with squamous cell carcinoma had similar 12m PFS rate with adenocarcinoma (77.8% vs 66.7%). 12m PFS rate was consistent across different biomarker status. OS data was immature and the estimated 12-month OS rate was 95.5% (95% CI, 71.9%, 99.3%). With more follow-up, grade ≥3 TRAE occurred in 54.4% patients, and grade ≥3 irAE was 4.5%. The most common irAE were hypothyroidism (50%), pneumonitis (13.6%), myositis (4.5%) and adrenal insufficiency (4.5%). Five patients required dose reduction of anlotinib and one patient had treatment discontinuation due to grade 3 rash.
ConclusionITT
（n=22）
PD-L1+
（n=13）
PD-L1 -
（n=8）
TMB ≥ 10
（n=6）
TMB ＜ 10
（n=10）
median PFS, m
(95% CI）
15
(8.3, NR)
NR
(7.7, NR)
14
(4.5, 15)
NR
(NR, NR)
14
(4.3, 15)
12 month PFS rate
(95% CI)
71.4%
(47.2%, 86.0%)
76.9%
(44.2%, 91.9%)
62.5%
(22.9%, 86.1%)
100%
(100%, 100%)
60.0%
(25.3%, 82.7%)
With longer follow-up, combination of sintilimab and anlotinib demonstrated durable efficacy and good tolerability. To our knowledge, this is the first study that assessed a PD-1 inhibitor plus an anti-angiogenesis TKI in first-line setting of advanced NSCLC. A phase II randomized trial (NCT04124731) is currently ongoing to further investigate this new chemo-free strategy.
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P14 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Immuno-Biology (ID 153)
- Event: WCLC 2020
- Type: Posters
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P14.29 - Toripalimab in Combination with CIK Cells in Patients with Advanced NSCLC: An Exploratory Study (ID 3349)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
Immune checkpoint inhibitors provide a new approach for the first-line treatment of advanced NSCLC (non-small cell lung cancer), with combination therapy based on checkpoint inhibitor being constantly explored. CIK (cytokine induced killer) immunotherapy, as a kind of adoptive immune cell therapy, has shown certain effects in previous clinical trials. The combination is theoretically synergistic, as PD-1 monoclonal antibody can restore the activity of T cells, and CIKs belongs to the T cell subgroup. There have been corresponding studies on PD-1 monoclonal antibody combined with CIK cells in the treatment of metastatic renal cell carcinoma to obtain better clinical effects, and whether CIK combined with PD-1 monoclonal antibody can improve survival in advanced NSCLC still needs further research.
Methods
This single-center, exploratory study aims to explore the safety and efficacy of toripalimab (240mg Q3W), a PD-1 antibody in combination with CIK cells (Q6W) in newly-diagnosed advanced NSCLC patients with positive PD-L1 expression (PD-L1>1%). The enrolled patients were randomly assigned to groups A, B and C: toripalimab + CIK (group A, n=20), toripalimab + CIK + chemotherapy (group B, n=20) and chemotherapy group (group C, n=20). The total number of CIK cells reinfused in each patient needs to be more than 1010. The primary endpoint is safety and progression free survival (PFS). The secondary endpoints include overall response rate (ORR), disease control rate (DCR), and overall survival (OS). Correlative studies will include evaluation of biomarkers and characterize the role of PD-L1 and TMB in this combination therapy. Enrollment for this trial is open in July of this year and will continue for 18 months.
Results
Not applicable.
Conclusion
Not applicable.
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P15 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Novel Immunotherapeutics (Phase I) (ID 154)
- Event: WCLC 2020
- Type: Posters
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P15.07 - Safety and Efficacy Profile of TQB-2450 Alone/with Anlotinib in Previously-Treated Advanced NSCLC: A Phase IB Single-Arm Trial (ID 3489)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
TQB-2450 is a novel humanized antibody, blocking programmed death-ligand 1 (PD-L1). Anlotinib, an oral multi-target tyrosine kinase inhibitor (TKI) approved by China National Medical Products Administration (NMPA), improved progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) in the phase 3 trial ALTER0303. Here, we report the safety and anticancer activity of TQB-2450 alone/with anlotinib hydrochloride in 3 cohorts for advanced/metastatic NSCLC patients without driver mutations.
Methods
Patients (18-75 ys, WHO PS 0/1, ≥1 measurable lesion defined by RECIST v1.1, ≥1 prior systemic therapy) without driver mutations were enrolled in this study (CTR20190336). Eligible patients received TQB-2450 (1200mg IV on Day 1 Q21D) alone/with anlotinib hydrochloride (10/12 mg QD from day 1 to 14 of a 21day cycle) until disease progression or treatment intolerance. The primary endpoint was PFS, secondary endpoints included safety, objective response (ORR), disease control rate (DCR) and OS.
Results
Until the 21st August 2020, a total of 51 pts were screened and 26 were finally enrolled. Median age was 62.5 years (range, 50-77); 84.62% male and 5/26 (19.23%) brain metastasis. 24/26 (92.31%) pts were response-evaluable. Among these pts, there was 0 CR, 6 PR, 18 SD and no disease progression, resulting in the objective response rate 25.00% and disease control rate 100.00 %. The most common Grade 3 treatment-related adverse effects (TRAE) were hypertension (12.00 %), pulmonary infection (12.00%), chest discomfort (8.00%), hypercalcemia (4.00%), vomiting (4.00%), poor appetite (4.00%) and chest pain (4.00%), and there were no grade 4/5 toxicities.
Conclusion
TQB-2450 alone/with anlotinib demonstrated a tolerable safety profile without grade 4/5 TRAE. Our results suggest that TQB-2450 alone/with anlotinib may represent a novel and safe treatment for advanced/metastatic NSCLC pts with prior systemic therapy.
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P26 - Mesothelioma, Thymoma and Other Thoracic Malignancies - Thymic Malignancies (ID 218)
- Event: WCLC 2020
- Type: Posters
- Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P26.05 - Comprehensive Genomic Sequencing in Thymic Epithelial Tumors: Identification of Multiple Poor Prognosis Biomarkers in Chinese Patients (ID 1831)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
Thymic squamous carcinomas (TSCC) and thymic neuroendocrine tumor (NETT) are two types of thymic tumor which have higher risk of relapse and death. TSCC is a malignant neoplasm of the thymus with morphological features of squamous cell carcinoma as seen in other organs. However, the research about genetic profile and its relationship with prognosis of both tumors are rare.
Methods
47 patients who diagnosed with TSCC/NETT at Shanghai Jiao tong University Affiliated Chest Hospital between 2015 and 2017 were sequenced by FoundationOne CDx (F1CDx) which is a FDA approved platform conducted by DIAN (Hangzhou Lab) with the licensed technologies. During the follow up, the clinical information and the survival information was also collected. The cox regression model was used to analyze the relationship between genomic alteration and the survival data.
Results
A total of 47 patients’ (including 29 men, 14 ever smokers) surgical specimens were sequenced. The histological types include TSCC(N=27), NETT (N=14) and mixed of both(N=6). The median age of TSCC, NETT and mixed subtype was 59.5, 65 and 74, respectively. The top ranked altered genes in TSCC were TP53 (30%), CDKN2A (26), CDKN2B (19%) and ASXL1 (15%). In NETT, the top mutated genes were MEN1 (36%), STAG2 (14%), CDKN2A (14%) and HRAS (14%). The top ranked mutated genes in mixed subtype were TP53 (29%) and CDKN2A (29%). Notably, TP53, ASXL1, TET2, MLL2, EP30, BAP1 were only mutated in TSCC or mixed subtypes. However, mutated of MEN1, STAG2 and HRAS were also founded in NETT subtype. The TMB of three groups have no significant differences. 13 of 47 patients (27.7%) showed CDKN2A deletion and 7 of 47 tumors (14.9%) showed CDKN2B deletion which both were correlated with worse recurrence-free survival (RFS) (P＜0.001). 5 (10.6%) patients showed MTAP loss, which was correlated with worse RFS (P =0.018). 6 (12.8%) patients showed TSC2 missense, which was correlated with worse RFS (P =0.017). 3 (6.4%) patients showed EPHB4 missense, which was also correlated with worse RFS (P =0.0081).
Conclusion
Our study found that: TSCC and NETT have very different gene alternation landscape, while the mixed subtype was more similar with TSCC than with NETT. The most altered genes are focused on signal pathways of cell cycle control, Chromatin remodeling/DNA methylation, PI3K/AKT1/MTOR, MAP kinase signaling and others.In addition, we firstly identified multiple poor prognosis biomarkers in Chinese thymic epithelial tumors patients. These poor prognosis biomarkers are mainly enriched in cell cycle control and PI3K/AKT1/MTOR pathways.
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P46 - Screening and Early Detection - Gene-Based Risk Stratification (ID 183)
- Event: WCLC 2020
- Type: Posters
- Track: Screening and Early Detection
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P46.04 - Identify Lung Adenocarcinoma among Pulmonary Micro-nodules through Blood Gene Expression Profiles (ID 1808)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
The national lung cancer screening test (NLST) confirmed: low dose CT screening could reduce lung cancer mortality. However, the high false-positive rates of LDCT screening, especially the difficulty of diagnosis of micro-nodules with size less than 10 mm highlight the need of complementary biomarkers to discriminate micro-nodular lung cancer from benign pulmonary diseases.
Methods
The blood gene expression of 114 lung cancer patients and 82 pulmonary lesions were investigated to identify the lung cancer-specific genetic signatures. The lung cancer patients containing micro-nodules less than 10 mm were surgically and pathologically diagnosed as lung adenocarcinoma in situ.
Results
A self-training logistic regression method was used to identify the lung cancer-specific gene signatures as we previously reported. Seven genes, including HNRNPD, TNFSF10, SLC38A1, MCEMPI, ZFN266, TRAF5, and MORF were identified for discriminating lung adenocarcinoma from benign pulmonary diseases. Through self-training SVM classifier, the logarithmic odds of each sample was calculated and exhibited, in which the cutoff value was set as zero in logarithmic odds for differentiating lung cancer from benign group. The predictive model based on 7-gene panel correctly classified 69 of 114 lung cancer, 69 of 82 benign pulmonary diseases with 84% specificity, 60% sensitivity, 70% accuracy, and 0.83 of ROC AUC.
Conclusion
The predictive model based on 7-gene panel (HNRNPD, TNFSF10, SLC38A1, MCEMPI, ZFN266, TRAF5, and MORF) can be used for discriminating between the malignant or benign nodules with size less than 10 mm.
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P46.05 - A Blood Six-Gene Test for Early-Stage Lung Adenocarcinoma Screening in Asympomatic Population (ID 1823)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
A 6-gene quantitative PCR expression assay has been developed for early-stage lung adenocarcinoma screening in an asymptomatic population based on 144 lung adenocarcinoma patients and 107 healthy volunteers with self-training logistic regression method. Validation in an independent cohort may consolidate the clinical effectiveness of the panel.
Methods
Single-blind molecular risk-stratification by the 6-gene quantitative PCR expression assay was performed on 122 histopathology-confirmed lung adenocarcinoma patients and 101 healthy volunteers.
Results
The predictive model based on 6-gene panel correctly classified 108 of 122 lung cancer with 88.5% sensitivity, 73.1% accuracy and 0.849 of ROC AUC.
Conclusion
The 6-gene quantitative PCR expression assay can be used as a non-radiative reinforcement of low dose CT for early-stage lung adenocarcinoma screening in an asymptomatic population.
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P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P48.09 - Anlotinib Plus Etoposide and Carboplatin as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer: A Single Arm Phase II Trial (ID 3487)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
Anlotinib is a novel multi-target tyrosine kinase inhibitor approved by NMPA (China National Medical Products Administration) and its anti-tumor vascular targets include VEGFR, PDGFR, c-Kit and FGFR. This phase II study aims to further evaluate the efficacy and safety of anlotinib plus etoposide and carboplatin in treatment-naïve patients with extensive-stage small cell lung cancer (ES-SCLC).
Methods
Treatment-naive pts (WHO PS 0/1) with ES-SCLC received anlotinib( 10 mg p.o, QD d1 to 14 of a 21-day cycle) +etoposide (100mg/m2,iv, d1~3, Q3W)+carboplatin(AUC = 5~6,iv, d1, Q3W) for 6 cycles followed by anlotinib maintenance until disease progression (PD) or intolerable adverse effect. The primary endpoint was PFS. Secondary endpoints are OS, ORR, DCR and safety.
Results
Up to Jul 2020, 20 ES-SCLC patients were enrolled and treated with anlotinib plus EC. Median age was 63 years (range 44-79); 95% male, 5% brain metastasis. 20% received radiotherapy. At data cutoff (Jul, 2020), patients were followed up for a median of 15.48 months. Median PFS was 11.43 months; ORR was 80% (0 CR, 16 PR), DCR was 90% (0 CR, 16 PR, 2 SD) and median OS was NE. Univariate analysis found that smoker achieved a significant longer mPFS than non-smoker (12.27 vs 3.62 months, HR：0.20). The most common Grade 3 AEs were neutropenia 35%, leukopenia 20%, hand-foot syndrome 15%, nausea 10%, fatigue 10%; epistaxis 5%; hemoptysis 5% and there were no grade 5 toxicities.
Conclusion
This study finds that anlotinib plus etoposide and carboplatin can significantly improve PFS compared to standard chemotherapy for treatment-naïve ES-SCLC pts. While with the approval of the immunotherapy in SCLC, further study would focus on the optimal treatment combination choice of ES-SCLC.
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P62 - Tumor Biology and Systems Biology - Basic and Translational Science - Metabolomics (ID 200)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P62.09 - PLGF Regulates Stimulation of Cell Proliferation and Glycolysis of Lung Adenocarcinoma Through Wnt/β-catenin Pathway (ID 3510)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
Angiogenic placental growth factor (PLGF) plays a role in hypoxia-induced angiogenesis. Here, we aimed to investigate the biological roles of PLGF in cell proliferation and glycolysis of lung adenocarcinoma (LUAD) and the underlying molecular mechanisms.
Methods
PLGF was knocked down in H358 and H1975 cells by lentiviruses, which were then cultured under hypoxia (90% N2, 5%CO2 and 5%O2) for 24 h. PLGF was overexpressed in PC9 cells treated with XAV939, inhibitor of Wnt/β-catenin signaling pathway. PLGF-silencing H1975 cells were implanted into mice, and tumor xenografts were harvested and analyzed.
Results
Hypoxia treatment led to up-regulation of PLGF, C-myc, lactate dehydrogenase A (LDHA), and β-catenin, promotion of cell proliferation and glycolysis inH358 and H1975 cells, which were obviously reversed by knocking down PLGF. In tumors, PLGF knockdown significantly prohibited cell proliferation and glycolysis, and decreased expression of C-myc, LDHA, and β-catenin. PLGF overexpression markedly strengthened cell proliferation and glycolysis, and increased β-catenin expressionin PC9 cells, which were abrogated by XAV939.
Conclusion
PLGF knockdown inhibited the stimulatory effect of hypoxia on cell proliferation and glycolysis of LUAD through deactivating Wnt/β-catenin pathway.
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P67 - Tumor Biology and Systems Biology - Basic and Translational Science - Proteomics (ID 206)
- Event: WCLC 2020
- Type: Posters
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P67.01 - Differential Proteomics Analysis on Plasma from Anlotinib-Treated Advanced Non-Small Cell Lung Cancer Patients (ID 1843)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
Anlotinib has been demonstrated to be effective in advanced non-small cell lung cancer (NSCLC) patients. DNA-seq- and RNA-seq-based anlotinib molecular mechanism and biomarker screening have been introduced in previous studies. The underlying value of proteomics for anlotinib study is still unclear.
Methods
In this study, 70 plasma samples were selected from 28 anlotinib-treated NSCLC patients (including 14 responders and 14 non-responders). LC-MS/MS analysis was performed on those samples with different time points including baseline, best response and progression disease. Bioinformatics analysis was performed to understand the underlying value of those differential proteins.
Results
Proteomics analysis suggested the differential proteins from responders after anlotinib administration potential play a role in the molecular mechanism characterization and biomarker screening. The differential proteins between responders and non-responders at baseline mainly contribute to biomarker screening. Integrative analysis indicated 43 proteins could be used as underlying biomarkers for clinical practice. Lastly, we selected ARHGDIB and demonstrated that it has potential predictive value for anlotinib.
Conclusion
This study not only offered the first insight that the proteomic technology potentially be used for anlotinib molecular mechanism characterization, but also provided a basis for anlotinb biomarker screening via proteomics in the future.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.10 - Erlotinib Plus Anlotinib as First-Line Therapy in Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: An Open-Label, Phase 2 Study (ID 1030)
00:00 - 00:00 | Author(s): Baohui Han
- Abstract
Introduction
The combination of erlotinib and bevacizumab significantly improved progression-free survival (PFS) compared with erlotinib monotherapy in NEJ026 and ARTEMIS study for advanced EGFR mutation-positive NSCLC patients. However, data of antiangiogenic multi-target tyrosine kinase inhibitor (TKI) plus EGFR TKI remains unknown. We aimed to firstly evaluate the efficacy and safety of the combination of erlotinib and anlotinib (an antiangiogenic multi-target TKI) in Chinese patients with advanced EGFR-mutated NSCLC.
Methods
In this open-label, phase 2 study, NSCLC patients with previously untreated, EGFR mutation (exon 19 deletion or L858R) received anlotinib (10 mg QD from day 1 to 14 of a 21-day cycle) and erlotinib (at a dose of 150 mg once daily) until disease progression or treatment intolerance. The primary outcome was objective response (ORR) and secondary outcomes were PFS, disease control rate (DCR) and overall survival (OS).
Results
A total of 60 patients were enrolled from October 2018 to November 2019. Among these patients, 35 (58.3%) patients were female. And 14 (23.3%) of them had brain metastasis. Till August 2020, 57 of the patients received at least once tumor assessment. 51 of them achieved partial response, 6 of them had stable disease and no patients had disease progression. The ORR was 89.5%, while the DCR was 100 %. The most common grade 3 adverse event (AE) are rash (15.3 %), oral mucositis (10.2%) and diarrhea (8.5 %). A grade 4 hypertension were observed.
Conclusion
This is the first study of the new combination of anlotinib plus erlotinib. The results suggest that this strategy could be a new first-line therapy in EGFR-mutated NSCLC patients. The long-term outcomes will be revealed in the future.
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P76.59 - Rationale and Design of a Phase II Trial of Dacomitinib in Advanced NSCLC Patients with Uncommon EGFR Mutations (ID 3206)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
Dacomitinib is a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). ARCHER-1050 suggested that dacomitinib can prolong progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer patients with 19del or 21L858R compared to standard first-generation EGFR-TKI. However, it is still unclear whether this agent is effective in patients with uncommon EGFR mutations in exon 18-21.
Methods
This is a single arm, prospective, open label and phase II trial. A total of 30 eligible patients will be recruited. Patients will receive continuous oral therapy with the study drugs (dacomitinib 45 mg) until disease progression, withdrawal of consent, or unacceptable toxicity. The primary endpoint is objective response rate (ORR) per RECIST version 1.1, as determined by investigators’ review. The second endpoint is disease control rate (DCR), PFS, OS, and safety.
The primary endpoint of the study is ORR as determined by investigators’ review. Sample size will be calculated by a minimax two-stage design method based on the following parameters: α=0.075, 1-β=0.9, P0=0.20, P1=0.45. The optimal two-stage design tests the null hypothesis that P ≤ 0.20 versus the alternative that P ≥ 0.45. After testing the drug on 12 patients in the first stage, the trial will be terminated if 2 or fewer patients respond. If the trial goes on to the second stage, a total of 27 patients will be studied. If the total number responding is less than or equal to 8, the drug is considered noneffective. Assuming a dropout rate of 10%, 30 patients will be finally enrolled.
Results
The study has been registered in clinicaltrial.gov and the registration number is NCT04504071. The study will recruit participants in September 2020 and is expected to take 26 months.
Conclusion
We conduct a phase II study to investigate the safety and efficacy of dacomitinib in advanced NSCLC patients with uncommon EGFR mutations.
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P80 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Chemotherapy/ Immunotherapy Plus Targeted Therapy (ID 257)
- Event: WCLC 2020
- Type: Posters
- Track: Immunotherapy (Phase II/III Trials)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P80.01 - A Multicenter, Randomized, Phase 3 Trial of Penpulimab in Combination With Anlotinib or Chemotherapy as First-Line Treatment in Advanced NSCLC (ID 3447)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
Penpulimab, a human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) directed against human programmed cell death-1 (PD-1), was engineered to optimize receptor occupancy by improving duration of drug binding, and to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function. Anlotinib, an antiangiogenic multi-target tyrosine kinase inhibitor. Chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). A combination of the PD-1 checkpoint inhibitor and the antiangiogenic drug may improve clinical response in NSCLC by blocking the accumulation of immunosuppressive cells and promoting influx of effector T cells into tumors. Combining penpulimab with chemotherapy may be synergistic as chemotherapy elicit anticancer immunity through release of potentially immunogenic tumour antigens. Promising early results were reported in a phase 1 study for Anlotinib plus Sintilimab (anti-PD-1) in 1L NSCLC: ORR 72.7%, DCR 100%, a 6-month PFS rate of 93.8%. This study aims to evaluate the efficacy and safety of penpulimab in combination with anlotinib or chemotherapy versus chemotherapy alone in patients with advanced non-squamous NSCLC who have not previously received systemic therapy. As of Aug 20, 2020, 11 patients treated with Penpulimab plus Anlotinib, 6 patients were evaluable for efficacy (4 achieved PR, and 2 achieved SD with tumor shrinkage).
Methods
This is a multicenter, randomized, three groups, phase 3 trial. Patients will be eligible for enrollment if they had histologically or cytologically confirmed diagnosis of stage IIIB/IIIC/IV non-squamous NSCLC without sensitizing mutation of the epidermal growth factor receptor gene(EGFR) or translocation of the anaplastic lymphoma kinase gene(ALK) and received no previous systemic therapy for advanced or metastatic NSCLC. Eligible patients will be randomly assigned, in a 1:1:1 ratio, to receive penpulimab plus anlotinib (AA), penpulimab plus carboplatin plus pemetrexed (ACP), or placebo plus carboplatin plus pemetrexed (PCP) every 3 weeks. Patients with AA will be treated until disease progression or discontinuation of treatment owing to toxic effects or for other reasons. Patients with ACP or PCP will be treated for four cycles, followed by maintenance therapy with penpulimab plus pemetrexed or placebo plus pemetrexed respectively. The primary endpoint is independent radiologic review committee (IRRC)-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). The key second endpoints include overall survival, IRRC-assessed objective response rate (ORR), disease control rate (DCR), response duration (DOR), time to response (TTR) and safety. Approximately 465 pts will be enrolled. clinical trial information: NCT03866980.
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P86 - Targeted Therapy - Clinically Focused - New Target (ID 263)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P86.16 - Rationale of a Phase II Trial of Nivolumab Combined with Anlotinib in Advanced NSCLC Previously Treated with Immunotherapy (ID 3209)
00:00 - 00:00 | Presenting Author(s): Baohui Han
- Abstract
Introduction
Immune check point inhibitors (ICIs) has revolutionized first-line treatment of advanced NSCLC patients. Antiangiogenic agent (e.g. anlotinib, lenvatinib) combined with ICIs have provided a promising therapeutic strategy. Our previous explanatory study suggested that anlotinib has staggering synergetic effect when combined with ICIs. Based on previous studies, we propose our hypothesis that nivolumab combined with anlotinib may confer survival benefit even in patients previously treated with ICIs because of the staggering synergetic effect, and may serve as a better second-line treatment.
Methods
This is a phase Ib/IIa, open-label, single center study, aiming to investigate safety and efficacy of nivolumab (administered intravenously) in combination with anlotinib (administered orally) in immunotherapy-treated advanced NSCLC. The study has been designed to allow an investigation of the optimal combination dose and schedule while ensuring the safety of patients with intensive safety monitoring. There are two main parts to this study; Part A, combination dose finding and Parts B, dose expansion. Part B will either be initiated if recommended phase 2 dose (RP2D) reached in Part A, or not initiated if RP2D was not reached in Part A.
The primary objective in part A is to define the RP2D of nivolumab combined with anlotinib, secondary objective is to investigate the safety and tolerability of nivolumab combined with anlotinib. The primary objective in part B is ORR, secondary objective is progression-free survival (PFS), disease control rate (DCR) and overall survival (OS).
Results
The study has been registered in clinicaltrial.gov and the registration number is NCT04507906. The study will recruit a total of 62 participants in September 2020 and is expected to take 35 months.
Conclusion
We conduct a phase II study to investigate the safety and efficacy of nivolumab combined with anlotinib in advanced non-small cell lung cancer patients previously treated with checkpoint inhibitors.
