Advanced NSCLC Patients Research Articles

C-MET Inhibitors as New Members of the NSCLC Treatment Armamentarium—A Pooled Analysis

Objective: Capmatinib and tepotinib, two recently FDA-approved and highly specific small-molecule inhibitors of c-MET exon 14 skipping mutations are new and important therapeutic options for the treatment of NSCLC patients harbouring c-MET alterations. However, the precise role of these molecules as a new treatment option is still not fully defined. Methods: In an attempt to further evaluate the contributions of c-MET inhibitors to the armamentarium of treatment options for advanced and metastatic NSCLCs, relevant phase II and III studies were retrospectively analyzed in terms of ORR and mPFS (mOS numbers are still not available for current c-MET trials and therefore not considered for statistical purposes). Results: Treatment of advanced and metastatic NSCLC patients harbouring c-MET exon 14 skipping mutations with the novel and highly selective c-MET inhibitors is significantly superior (p < 0.0001) when compared with standard chemotherapy. However, when c-MET inhibitors are compared with immunotherapy or the combination of immunotherapy and chemotherapy, no significant differences in terms of ORR and PFS were found, but treatment with c-MET reported be much more tolerable. Conclusion: The novel and highly selective c-MET inhibitors capmatinib and tepotinib are promising novel treatment options for patients with c-MET-dysregulated NSCLC primarily in the first-line setting, albeit a clear mOS benefit has not yet been established. Since immunotherapy did not appear to be particularly effective in NSCLC patients harbouring c-MET alterations, the vast majority of these patients are treated with immunotherapy plus chemotherapy. C-Met inhibitors appear to be equally effective and thereby sparing patients from the toxic effects of the chemotherapy. The routine testing of c-MET exon 14 skipping mutations should be performed as the GEOMETRY mono-1 data clearly showed higher response rates with capmatinib in treatment-naive than in pretreated patients, indicating that c-MET exon 14 skipping mutations should preferably be molecularly assessed at baseline. C-MET exon 14 skipping mutations are, therefore, clear biomarkers of response to c-MET inhibitors.

Machine Learning Based on Blood Test Biomarkers Predicts Fast Progression in Advanced NSCLC Patients Treated with Immunotherapy

Machine Learning Based on Blood Test Biomarkers Predicts Fast Progression in Advanced NSCLC Patients Treated with Immunotherapy

Front-Line Therapy in EGFR Exon 19 Deletion and 21 Leu858Arg Mutations in Advanced Non-Small Cell Lung Cancer: A Network Meta-Analysis

Objective This study aimed to compare the efficacy of different first-line strategies based on different EGFR mutation types (19 deletion and 21 Leu858Arg mutations). Methods We conducted a systematic review and network meta-analysis (NMA) by searching and analyzing RCTs on PubMed, Embase, Cochrane Library, ASCO.org, and ESMO.org, from inception to September 30th, 2020. Results Nineteen RCTs involving 5450 patients were finally included in this study, covering 10 different treatment strategies. The Bayesian ranking results suggested that, in terms of PFS, in the overall population and in patients with 19del mutation, osimertinib was most likely to rank the first, with the cumulative probabilities of 41.89% and 45.73%, respectively, while for patients with 21 Leu858Arg mutation, standard of care (SoC, represents first-generation EGFR-TKIs in this NMA) + chemotherapy was most likely to rank the first, with the cumulative probabilities of 30.81% in PFS. Moreover, SoC + chemotherapy provided the best overall survival benefit for the overall population and patients with 19del, with the cumulative probabilities of 57.85% and 33.51%, respectively. In contrast, for patients with 21 Leu858Arg mutation, dacomitinib showed the most favorable overall survival, with the cumulative probabilities of 36.73%. Conclusions In this NMA, osimertinib and SoC combined with chemotherapy would be the optimal first-line treatment options for advanced NSCLC patients harboring EGFR 19 deletion mutation and 21 Leu858Arg mutation, respectively. This finding is likely to be adopted in clinical practice and provide guidance for future clinical study design. Systematic review registration: INPLASY2020100059.

17P Dynamic changes of CT-radiomic and systemic immune-inflammatory features predict the response to immune checkpoint inhibitors in advanced NSCLC patients

Clinically suitable biomarkers to foresee the response to immune checkpoint inhibitors (ICIs) can be achieved by decoding tumor heterogeneity and its evolution during treatment. Thus, we determine whether the longitudinal assessment of radiomic features (RFs) and blood hallmarks of systemic inflammation (SI) may predict ICI efficacy in advanced NSCLC.

96P US real-world immunotherapy-based treatment patterns and clinical outcomes of advanced NSCLC (aNSCLC) patients in the first-line setting

Immunotherapy (IO) in the first-line (1L) setting has improved outcomes in patients (pts) with aNSCLC in clinical trials and is now a standard of care. To understand IO use in the real world (RW), we assessed treatment patterns and clinical outcomes of US aNSCLC pts receiving 1L IO treatment.

148P A phase II study of tislelizumab plus chemotherapy in EGFR mutated advanced non-squamous NSCLC patients failed to EGFR TKI therapies: First analysis

BackgroundAlthough EGFR tyrosine kinase inhibitors (TKI) have improved the survival of EGFR mutated NSCLC pts, drug resistance inevitably develops in almost all pts. Tislelizumab (tis), an anti-PD-1 mAb, has shown improved efficacy when combined with chemotherapy in pts with advanced EGFR-wt NSCLC with a tolerable safety profile. This study aims to evaluate the efficacy and safety of tis plus chemotherapy in EGFR-mut nsq-NSCLC pts failed to EGFR TKI therapies.MethodsThis multicenter, single-arm, phase II study enrolled pts with EGFR sensitizing mutations who have failed prior EGFR-TKI therapies. Pts were treated with tis plus carboplatin and nab-paclitaxel Q3W for up to 4 cycles, followed by tis plus pemetrexed maintenance therapy. Primary endpoint was 1-year PFS rate, and secondary endpoints included ORR, DCR and safety, etc. First analysis is planned at 7 weeks after 50% planned enrollment (33 pts) for early efficacy and safety.ResultsTable: 148PResponseTotal (N=32)EGFR mutation#Prior EGFR TKI treatmentprior anti-angiogenesis treatmentExon 19del (N=17)Exon 21 L858R (N=14)1/2nd and 3rd TKI (N=17)1/2nd or 3rd TKI (N=15)Yes (N=10)No (N=22)BoR, n (%)PR19 (59.4%)∗12 (70.6%)6 (42.9%)10 (58.8%)9 (60.0%)7 (70.0%)12 (54.6%)SD10 (31.3%)3 (17.7%)7 (33.3%)5 (29.4%)5 (33.3%)1 (10.0%)9 (40.9%)PD3 (9.4%)2 (11.8%)1 (7.1%)2 (11.8%)1 (6.7%)2 (20.0%)1 (4.6%)ORR19 (59.4%)12 (70.6%)6 (42.9%)10 (58.8%)9 (60.0%)7 (70.0%)12 (54.6%)DCR29 (90.6%)15 (88.2%)13 (92.9%)15 (88.2%)14 (93.3%)8 (80.0%)21 (95.5%)BOR, best overall response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate*Including 4 unconfirmed PR;#1 pts with exon 18 G719X was PR. Open table in a new tab ConclusionsTislelizumab plus chemotherapy has preliminarily shown a promising anti-tumor efficacy with manageable safety profile for EGFR TKI failure pts. Efficacy and safety of the combination will be continuously monitored.Clinical trial identificationNCT04405674.Legal entity responsible for the studyThe authors.FundingBeiGene (Beijing), Co. Ltd.DisclosureAll authors have declared no conflicts of interest. BackgroundAlthough EGFR tyrosine kinase inhibitors (TKI) have improved the survival of EGFR mutated NSCLC pts, drug resistance inevitably develops in almost all pts. Tislelizumab (tis), an anti-PD-1 mAb, has shown improved efficacy when combined with chemotherapy in pts with advanced EGFR-wt NSCLC with a tolerable safety profile. This study aims to evaluate the efficacy and safety of tis plus chemotherapy in EGFR-mut nsq-NSCLC pts failed to EGFR TKI therapies. Although EGFR tyrosine kinase inhibitors (TKI) have improved the survival of EGFR mutated NSCLC pts, drug resistance inevitably develops in almost all pts. Tislelizumab (tis), an anti-PD-1 mAb, has shown improved efficacy when combined with chemotherapy in pts with advanced EGFR-wt NSCLC with a tolerable safety profile. This study aims to evaluate the efficacy and safety of tis plus chemotherapy in EGFR-mut nsq-NSCLC pts failed to EGFR TKI therapies. MethodsThis multicenter, single-arm, phase II study enrolled pts with EGFR sensitizing mutations who have failed prior EGFR-TKI therapies. Pts were treated with tis plus carboplatin and nab-paclitaxel Q3W for up to 4 cycles, followed by tis plus pemetrexed maintenance therapy. Primary endpoint was 1-year PFS rate, and secondary endpoints included ORR, DCR and safety, etc. First analysis is planned at 7 weeks after 50% planned enrollment (33 pts) for early efficacy and safety. This multicenter, single-arm, phase II study enrolled pts with EGFR sensitizing mutations who have failed prior EGFR-TKI therapies. Pts were treated with tis plus carboplatin and nab-paclitaxel Q3W for up to 4 cycles, followed by tis plus pemetrexed maintenance therapy. Primary endpoint was 1-year PFS rate, and secondary endpoints included ORR, DCR and safety, etc. First analysis is planned at 7 weeks after 50% planned enrollment (33 pts) for early efficacy and safety. ResultsTable: 148PResponseTotal (N=32)EGFR mutation#Prior EGFR TKI treatmentprior anti-angiogenesis treatmentExon 19del (N=17)Exon 21 L858R (N=14)1/2nd and 3rd TKI (N=17)1/2nd or 3rd TKI (N=15)Yes (N=10)No (N=22)BoR, n (%)PR19 (59.4%)∗12 (70.6%)6 (42.9%)10 (58.8%)9 (60.0%)7 (70.0%)12 (54.6%)SD10 (31.3%)3 (17.7%)7 (33.3%)5 (29.4%)5 (33.3%)1 (10.0%)9 (40.9%)PD3 (9.4%)2 (11.8%)1 (7.1%)2 (11.8%)1 (6.7%)2 (20.0%)1 (4.6%)ORR19 (59.4%)12 (70.6%)6 (42.9%)10 (58.8%)9 (60.0%)7 (70.0%)12 (54.6%)DCR29 (90.6%)15 (88.2%)13 (92.9%)15 (88.2%)14 (93.3%)8 (80.0%)21 (95.5%)BOR, best overall response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate*Including 4 unconfirmed PR;#1 pts with exon 18 G719X was PR. Open table in a new tab BOR, best overall response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate *Including 4 unconfirmed PR; #1 pts with exon 18 G719X was PR. ConclusionsTislelizumab plus chemotherapy has preliminarily shown a promising anti-tumor efficacy with manageable safety profile for EGFR TKI failure pts. Efficacy and safety of the combination will be continuously monitored. Tislelizumab plus chemotherapy has preliminarily shown a promising anti-tumor efficacy with manageable safety profile for EGFR TKI failure pts. Efficacy and safety of the combination will be continuously monitored.

Tailoring maintenance chemotherapy upon response to induction chemotherapy as compared with pemetrexed continuation maintenance in advanced non-squamous NSCLC patients: Results of the IFCT-GFPC-1101 multicenter randomized phase III trial

BackgroundBenefit from maintenance in advanced non-squamous non-small cell lung cancer (NS-NSCLC) might favor switch maintenance after disease stabilization (SD) and continuation after objective response (OR). This trial assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG) with G continuation for patients with OR or switch to pemetrexed (P) for patients with SD as compared with a control arm based on the Paramount regimen. MethodsEligibility criteria: age 18–70 years, ECOG PS 0–1, untreated stage IV NS-NSCLC without EGFR or ALK alteration, ineligibility to bevacizumab. Patients were randomized 1:1 to receive either CG (4 cycles) followed by G maintenance in case of OR followed by P at progression, or switch to P for patients with SD, or 4 cycles of CP followed by P (control arm). Primary endpoint: overall Survival. ResultsBetween 2012 and 2016, 932 patients were randomized (CG: 467, CP: 465) with well-balanced characteristics. 257 patients (56.7%) in the CG arm received maintenance (G: 142, P: 113) versus 277 patients (59.7%) in the CP arm. Median number of maintenance cycles was 5 for G and P (CG induction) and 4 for P (CP induction). OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p = 0.71) with a median of 10.9 months (CG) versus 10.4 (CP). HR for PFS was 0.95 (95% CI 0.83, 1.09; p = 0.45) with a median of 4.8 months for CG versus 4.5 for CP. Safety profile was as expected. ConclusionsAdapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome. Clinical trial information: NCT01631136.

Fully Automated Workflows Quantify and Report Key T-Cell and B-Cell Receptor Biomarkers Relevant to Immuno-Oncology and Heme-Oncology Research

BackgroundT-cell and B-cell repertoire analysis is used in oncology research, to understand the etiology of complex disease phenotypes, for the identification of biomarkers predictive of disease burden, outcome, and response to treatment, and for research in diagnosis and recurrence monitoring. Key predictors include secondary and tertiary repertoire features not reported by existing sequencing software solutions. For example, due to ongoing somatic hypermutation in mature B-cell receptors, the underlying sequence of a given clone can accumulate base differences and appear as several distinct clones with smaller frequencies, thereby hampering the ability of analysis software to detect its presence as a single dominant clone with the highest frequency. This has particularly detrimental implications for research in disorders such as follicular lymphoma and may require clonal lineage analysis for proper mitigation. Therefore, to aid the downstream analytics of biomarker identification and the study of complex disease, we developed fully automated analysis solutions that directly compute and report several key features (clonal lineage, amongst several others described below) pertinent to this area of research.ResultsWe developed the Oncomine™ TCR Beta-SR, TCR Gamma-SR, BCR IGH-SR and BCR IGKL-SR workflows on Ion Reporter™ to characterize T-cell (β, γ chains) and B-cell (heavy and light (κ, δ) chains) repertoires. These workflows generate output tables and visualizations for primary repertoire features such as detected clones (viz., unique rearrangements in the receptor DNA sequence), their frequencies, as well as their somatic hypermutation levels in the case of B-cells (Figure 1a & 1b) for clonality assessment and rare clone detection. The software also quantifies and reports several secondary and tertiary repertoire features in a sample, such as clonal diversity, evenness of the clonal population, and B-cell lineage groupings useful in identifying related sub-clones. It includes spectratyping format plots to simultaneously assess the above features as a function of v-gene usage and CDR3 length combinations (Figure 1c & 1d), thereby providing users a complete snapshot of the repertoire, and also the capability to quickly determine CDR3 lengths and V-gene usage of highly expanded or mutated clones. A separate CDR3 lengths histogram is included, as well as a heatmap that depicts the distributions/intensity of Variable-Joining gene combinations (Figure 1e & 1f).Furthermore, the TCR workflows also report (i) convergence frequencies (fraction of clones with different nucleotide sequences, but identical amino acid sequences), and (ii) haplotype grouping for an analyzed sample, based on V-gene allele genotyping and clustering (Figure 1g). In addition, the long read Oncomine™ BCR IGH-LR workflow uniquely reports the isotype class for every detected clone, and includes a visualization of total reads, clones and lineages in the sample represented by isotype (Figure 1h).ConclusionThe Oncomine™ immune repertoire workflows for T-cell and B-cell receptor sequencing were designed to be of high utility in distinct areas of malignancy research, and we expect them to greatly simplify complex downstream analyses. The unique capabilities of the workflows to automatically report secondary and tertiary repertoire features such as (i) clonal lineages for improved dominant clone detection in blood cancers, (ii) TCR clone convergence for prediction of response to immune checkpoint inhibitors [1,2], (iii) TCR haplotype grouping for evaluation of risk factors for autoimmunity and immune-related adverse events [3], and (iv) isotype classification in BCRs for studying pan-cancer immune evasion mechanisms, demonstrate the clear advantages of using these automated workflows over other existing solutions.For research use only.References1) Looney TJ et al. (2020) TCR Convergence in Individuals Treated With Immune Checkpoint Inhibition for Cancer. Front. Immunol. 10:2985.2) Naidus et al. (2021) Early changes in the circulating T cells are associated with clinical outcomes after PD-L1 blockade by durvalumab in advanced NSCLC patients. Cancer Immunology, Immunotherapy 70:2095-21023) Looney TJ et al. (2019) Haplotype Analysis of the T-Cell Receptor Beta (TCRB) Locus by Long-amplicon TCRB Repertoire Sequencing. Journal of Immunotherapy and Precision Oncology. 2 (4): 137-143. [Display omitted] DisclosuresSarda: Thermo Fisher Scientific: Current Employment. Lowman: Thermo Fisher Scientific: Current Employment. Toro: Thermo Fisher Scientific: Current Employment. Pickle: Thermo Fisher Scientific: Current Employment. Looney: Thermo Fisher Scientific: Ended employment in the past 24 months; Singular Genomics: Current Employment. Hyland: Thermo Fisher Scientific: Current Employment.

O13‐2: Two year follow‐up data of first‐line pembrolizumab for advanced NSCLC patients with PD‐L1 TPS of 50% or greater

O13‐2: Two year follow‐up data of first‐line pembrolizumab for advanced NSCLC patients with PD‐L1 TPS of 50% or greater

To Evaluate the Efficiency and Safety of Nab-paclitaxel Plus Cisplatin and Concomitant Thoracic Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> To evaluate the efficiency and safety of Nab-paclitaxel plus cisplatin and concomitant thoracic radiotherapy in locally advanced non-small-cell lung cancer. <h3>Materials/Methods</h3> A total of 68 cases locally advanced NSCLC patients were enrolled in this study, and 38 cases were enrolled so far (1:1 in the experimental group and the control group, 19 cases in each group, 1 case in each group did not complete the treatment, a total of 36 cases were available for statistical analysis). The control group received paclitaxel combined with cisplatin regimen chemotherapy (paclitaxel 175mg/m² on day 1, cisplatin 75mg/m² on day 2; every 3-4 weeks for 2 consecutive cycles. Experimental group: nab-paclitaxel weekly at a dose of 40mg/m², Cisplatin 75mg/m² and repeated every 3-4 weeks for 2 consecutive cycles. Both groups received concomitant aggressive radical three-dimensional thoracic radiotherapy with continuously accelerated hyperfractionation. The primary endpoint was ORR and safety (including treatment-induced bone marrow suppression, the toxicity of liver and kidney function, cardiotoxicity, radiation pneumonia, and other toxic side effects). Secondary endpoints were local progression-free survival rate, the local recurrence rate of the primary tumor, and the local control rate of the primary tumor. <h3>Results</h3> 38 patients completed concomitant chemoradiotherapy. The effective rates ORR of experimental group and control group were 89.6% and 68.5%, respectively. The short-term efficacy was CR (0 cases 0%, 1 case 5.2%), PR (17 cases 89.6%, 12 cases 63.3%), SD (1 case 5.2%, 5 cases 26.3%), PD (1 case 5.2%, 1 case 5.2%) <i>P</i> = 0.001. Grade 3/4 leukopenia 2 (10.5%), 14 (73.7%), <i>P</i> = 0.001; grade 3/4 neutropenia 2 (10.5%), 14 (73.7%), <i>P</i> = 0.001; grade 3/4 anemia 1 (5.3%) and 2 (10.5%), <i>P</i> = 0.547; grade 3/4 thrombocytopenia 0(0%) and 2 (10.5%) of, <i>P</i> = 0.146. There were 11 (57.9%) and 6 (31.6%) of grade I radiation esophagitis, and 8 (42.1%) and 13 (68.4%) of grade II esophagitis respectively. No grade III-IV esophagitis was found. <h3>Conclusion</h3> The ORR and short-term efficiency of nab-paclitaxel plus cisplatin concomitant radiotherapy are better than the control group, and the hematological toxicity is lower than the control group.

Association Between Changes in Myocardial F-18 Fluorodeoxyglucose Uptake and Cardiac Toxicity or Overall Survival for Inoperable NSCLC Patients Receiving Chemoradiation

<h3>Purpose/Objective(s)</h3> Previous studies have shown that increased cardiac uptake of 18F-fluorodeoxyglucose (FDG) on positron emission tomography (PET) may be an indicator of myocardial injury after radiotherapy. Our study aimed to investigate the predictive value of changes in myocardial ¹⁸F-FDG uptake for cardiotoxicity and overall survival (OS) in patients with inoperable NSCLC receiving definitive chemoradiation. <h3>Materials/Methods</h3> One hundred and fifty unresectable locally advanced NSCLC patients enrolled in a retrospective study who had undergone pre- and post-chemoradiation FDG-PET imaging were evaluated. Our primary endpoint was grade ≥ 3 cardiac toxicity. Patient clinicopathologic factors, dosimetric parameters for the whole heart and cardiac substructures, and myocardial changes within the irradiated fields on 18F-FDG PET were utilized to seek the best predictive model for cardiotoxicity. Competing risk analysis and Cox regressions analysis were performed. <h3>Results</h3> At a median follow-up interval of 35 months, twenty-six patients (17.3%) developed grade ≥ 3 cardiac everts. Twenty-nine patients (19.3%) showed increased myocardial FDG uptake within the irradiated fields associated with the heart dosimetric parameters. The best multivariable model based on the lowest Akaike information criterion for predicting grade ≥ 3 cardiotoxicity included the following covariates: pre-existing cardiac disease, changes in pre- and post-chemoradiation myocardial SUV_mean (∆SUV_mean), and mean heart dose. Subanalysis showed that pre-existing cardiac disease, ∆SUV_mean, and mean left anterior descending dose were significantly associated with grade ≥ 3 acute coronary syndrome/congestive heart failure events. ∆SUV_mean and grade ≥ 3 cardiac toxicity were independent indicators of OS. <h3>Conclusion</h3> ∆SUV_mean was an independent indicator of grade ≥ 3 cardiac toxicity and OS in unresectable locally advanced NSCLC patients receiving definitive chemoradiation. Changes in myocardial uptake of FDG is a promising biomaker for predicting radiation-induced cardiotoxicity.

PD-L1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer in PD-L1 Positive Patients: A Safety Data Network Meta-Analysis.

This network meta-analysis (NMA) evaluates the safety of first-line programmed death-ligand 1 (PD-L1) inhibitor monotherapy in advanced NSCLC patients compared to platinum-based chemotherapy. We also compared the risk of adverse events (AEs) according to programmed cell death-1 receptor (PD-1) or PD-L1 inhibitors therapy. To that end, we conducted a series of metanalyses (MAs) using data from six phase III clinical trials, including 4053 patients. Our results show a reduced risk of any grade treatment-related AEs (risk ratio (RR) = 0.722 95% CI: 0.667–0.783, p = 0.002), and grade 3–5 AEs (RR = 0.406 95% CI: 0.340–0.485, p = 0.023) in immunotherapy as compared to chemotherapy. In contrast, a higher risk of immune-related AEs (irAEs) was estimated for immunotherapy versus chemotherapy. The subgroup MAs comparing PD-L1 to PD-1 inhibitors, determined a lower risk of AEs leading to treatment discontinuation in the anti-PD-L1 subgroup (RR = 0.47 95% CI: 0.29–0.75, p = 0.001); however, this statistically significant difference between anti-PD-L1 and anti-PD-1 subgroups was not reached for other safety outcomes analyzed. In conclusion, our findings show that PD-L1 inhibitor monotherapy improves safety outcomes in the 1L treatment of advanced NSCLC patients as compared to chemotherapy except for irAEs.

P19.02 Sintilimab Plus Docetaxel in Previously Treated Advanced NSCLC, Updates on Progression-Free and Overall Survival

Background: Our phase single-arm phase 2 study previously showed favorable efficacy of sintilimab plus docetaxel as second line therapy for advanced Chinese NSCLC patients. Here we presented the updated survival and safety data. Eligible patients were standard platinum doublet failure advanced NSCLC patients, who had not received any ICIs before. EGFR/ALK positive patients must be TKIs failure or intolerable. Participants would receive docetaxel (75mg/m2, day 1) plus sintilimab (200mg, day 3) every 3 weeks for 4-6 cycles followed by sintilimab maintenance until disease progression, unacceptable toxicity, or up to 2 years. The primary end point is progression-free survival (PFS) per RECIST v1.1. Secondary end points included overall response rate (ORR), duration of response (DOR), overall survival (OS), and safety. From 10/2019 to 11/2020, 40 patients were enrolled. Most were male (77.5%) and adenocarcinoma (87.5%). 25% (10/40) patients and 12.5% (5/40) had brain and liver metastasis at baseline, separately. Median follow-up was 9.0 months (range 1.6-16.2) as of data cut-off (2/19/2021). 13 patients temporarily suspended study treatment due to COVID-19, while 11 patients resumed treatment after documented progression-free. Among all, 9 patients were still on study treatment until data cut-off. Median PFS was 5.78 months (95%CI 4.3-8.28), and PFS rates at 6 months and 12 months were 47% and 23%. Median OS was 12.45 months (95%CI 5.82-12.62). 12 months OS rates was 64%. Of the 37 evaluable patients, ORR is 32.43% (95%CI 18.01%, 49.79%), DCR is 89.19% (95%CI 74.58%, 96.97%). Median DOR was 6.46 months (95% 1.28, NA). Median TTR (Time to Response) was 3.89 months (95% 1.61, 4.99). Efficacy of key subgroups are presented in Table 1.Table 1Selected subgroup analysis of Sintilimab Plus Docetaxel efficacy in Treated NSCLCSubgroupCategoryNORR%(95%CI)mPFS months(95%CI)Histological typeAdenocarcinoma3533.33(17.96,51.83)5.78(4.14,8.28)Squamous cell carcinoma525(0.63,80.59)8.46(2.3,NA)Smoking statusYES2230(11.89,54.28)5.72(3.02,6.51)NO1835.29(14.21,61.67)8.28(4.14,9.36)Brain/meningeal metastasisNO3031.03(15.28,50.83)5.78(3.55,8.77)YES1037.5(8.52,75.51)6.51(1.58,NA)Driver gene mutationKRAS +625(0.63,80.59)6.51(2.96,NA)EGFR-and TP53+1937.5(15.2,64.57)5.78(3.55,9.36)Best overall response of first-line treatmentPR640(5.27,85.34)5.22(2.3,NA)SD1341.67(15.17,72.33)8.77(4.3,NA)PD1145.45(16.75,76.62)8.28(1.58,NA)First-line treatment (EGFR wild type)Chemotherapy2436.36(17.2,59.34)8.28(4.3,12.62)Chemotherapy +Bevacizumab1236.36(10.93,69.21)5.72(1.77,6.01)Best overall response of study treatmentPR11-NA(5.52,NA)SD21-4.86(3.55,6.01)Maximum change of target lesions from baseline≤ 20%19-8.77(5.78,NA)≤0%29-8.28(5.52,12.62)>0%8-2.37(1.02,NA) Open table in a new tab Median treatment duration was 4.4 months (range 0.1-13.9). Overall, 72.5% (29/40) patients had experienced treatment-related adverse events (TRAEs), including 15% (6/40) grade ≥3 TRAEs. No AEs led to treatment discontinuation or death. The most common TRAEs were leukopenia (32.5%), neutropenia (17.5%), alopecia (12.5%), lymphopenia (7.5%), fatigue (7.5%) and diarrhea (7.5%). 27.5% (11/40) patients experienced potential immune related AEs (irAEs), including 1 grade 3 gamma-glutamyltransferase increase, 1 grade 2 hypothyroidism and 3 grade 2 pneumonitis. This is the first study of a PD-1 inhibitor plus chemotherapy in advanced Chinese NSCLC patients who had failed first-line standard therapy. The encouraging efficacy and tolerable safety profile suggest a potential role of this combination in second-line setting. Clinical trial information: ChiCTR1900027634.

P40.14 Efficacy and Safety of Endostar Combined With Camrelizumab and Chemotherapy in Treatment of Advanced NSCLC: A Multi-Center Retrospective Study

Both Recombinant human endostatin (Endostar) and Camrelizumab have been approved in combination with chemotherapy in treatment of NSCLC in China. This study aims to observe the efficacy and safety of endostar plus Camrelizumab and chemotherapy in treatment of advanced NSCLC. This is periodic result. This is a multi-center, retrospective study. Advanced NSCLC patients (pts) who received endostar plus Camrelizumab and chemotherapy at least 2 courses were collected from December 2019. After two courses, the follow-up therapy will be decided by investigators. Baseline characteristics, efficacy evaluation and safety data were analyzed. Tumor response was evaluated according to RECIST 1.1. Adverse events (AEs) were graded according to NCI-CTC AE 4.0. The primary endpoint was progress-free survival (PFS), overall response rate (ORR), duration of response (DOR), overall survival (OS) and safety were included among secondary endpoint. Untill Mar. 2021, 21 pts were enrolled, and 17 pts were analyzed. The median age of pts was 55 years. 71% was male, 90% was diagnosed at stage IV. 76% was adenocarcinoma and 19% was squamous cell carcinoma. 67% received endostar combined with Camrelizumab and chemotherapy as first-line. The ORR and DCR is 71% and 100% respectively, with one CR patient. The treatment of 52% (11) pts is ongoing and the median PFS was not reach. In the safety-evaluable population, the most common AEs is thrombocytopenia (24%，>3 grade 10%), nausea and vomiting(24%，>3 grade 5%) and liver damage (19%). One pt was considered as immune-related hepatitis. Reactive cutaneous capillary endothelial proliferation (RCCEP) caused by Camrelizumab is 10% and none in >3 grade AEs.View Large Image Figure ViewerDownload Hi-res image Download (PPT) This retrospective study showed a promising efficacy and a good tolerance in advanced NSCLC pts with Endostar plus Camrelizumab and chemotherapy. This combined treatment maybe a new choice and we look forward to prospective study in furture.

P42.03 Predictive Factors of Response to PD-(L)1 Inhibitors in Patients With Advanced Non-Small Cell Lung and High PD-L1 Expression

Tumor PD-L1 expression is the only validated predictive biomarker in advanced NSCLC patients (pts) treated with PD-(L)1 inhibitors. Analysis of PD-L1 expression by immunohistochemistry has been validated in histological samples. Smoking and overweight have been described as predictive factors of better outcome, whereas bone metastases, antibiotics, corticosteroids and proton pump inhibitors as possible negative predictive factors. The aim of our study was to analyze different potential predictive factors to PD-(L)1 inhibitors in pts with advanced NSCLC and high PD-L1 expression. This retrospective study was carried out in pts with advanced NSCLC and high PD-L1 expression treated with PD-(L)1 inhibitors with median follow-up of 12.8 months [3.6-73.9]. Clinical and histological variables of interest were registered. Kaplan-Meier estimations were used to calculate survival, while the log-rank test was implemented to make comparisons. The impact of variables on survival was assessed through univariate and bivariate analysis. We included 86 pts, the mean age was 66 y [36-84], 24.4% were females, 73.3% were former smokers and 22.1% current smokers, 38,4% presented normal Body Mass Index, 79% pts had non-squamous NSCLC, and 12% pts had cytological sample for PD-L1 determination. 72 (83.7%) pts received monotherapy with PD-(L)1 inhibitor, 4 (4.7%) pts chemotherapy plus PD-(L)1 inhibitor and 10 (11.6%) pts received PD-(L)1 inhibitors with other immunotherapy drug. The median OS and PFS were 23.0 months (95% CI, 13.7 to 32.4) and 9.5 months (95% CI, 2.3 to 16.7), respectively. ORR and DCR in overall patients were 55.6% and 71.5%, respectively. The median OS in complete/partial response vs. stable disease vs. progression disease was not reached vs. 14.0 months (95% CI, 8.1 to 19.8) vs. 4.2 months (95% CI, 2.6 to 8.0), respectively (P<0,001). The median OS in patients receiving treatment beyond progression was not reached vs. 10.4 months (95% CI, 8.2 to 12.6) in patients that stopped treatment (P<0,001). A trend to better results were observed in patients with overweight or smokers, and a trend to worse OS was observed in pts with bone metastasis. No differences in OS were observed according to the tumor sample (cytological vs histological samples). Response to immunotherapy and treatment beyond progression were predictive of better outcome in pts with advanced NSCLC and high PD-L1 expression. No significant differences in survival were observed according to the type of tumor sample or clinical characteristics.

MA13.02 Phase II Study of Nivolumab and Ipilimumab Combined With Nintedanib in Recurrent Non-Small Cell Lung Cancer

Cancer-associated fibroblasts (CAFs) are a key immunosuppressive component of the tumor microenvironment (TME). Nintedanib is an oral triple kinase inhibitor that suppresses CAFs. Modulating the TME through inhibition of CAFs may represent an important synergistic approach in overcoming resistance to immune checkpoint inhibitors (ICIs). Based on these observations, we initiated a phase IB/II trial to evaluate the combination of nintedanib, nivolumab, and ipilimumab in advanced NSCLC patients. The phase IB dose-escalation results were presented at WCLC 2019 and the combination of nivolumab at 3mg/kg every 2 weeks, ipilimumab 1 mg/kg every 6 weeks, and nintedanib 150 mg once daily was declared as the recommended phase II dose (RP2D). Here we present the 1st interim analysis of phase II of the combination regimen in the ICI pre-treated patients. This is a single institution, investigational, non-randomized, parallel assignment phase I/II clinical trial of patients with locally advanced or metastatic NSCLC. Eligible patients can be immunotherapy naïve (Arm A) or with disease progression following immunotherapy (Arm B). Enrollment into phase II of the trial is being performed by the Bayesian two-stage design method with the primary objective of determining the efficacy of the combination regimen in NSCLC. Key secondary objectives are overall survival (OS) and progression-free survival (PFS). Descriptive statistics were used to summarize demographic and safety data. The Kaplan–Meier method with log-rank test was used for survival analysis. 20 patients received therapy with the combination of nivolumab, ipilimumab, and nintedanib at the RP2D in the ICI pretreated cohort (Arm B). The majority of patients were female (60%) with a current or prior history of tobacco use (84%) and an ECOG performance score of 1 (90%). Adenocarcinoma was the most common histology (75%). The most common treatment-related adverse event of any grade were transaminitis, diarrhea, and pruritis, each observed in 20% (4/20) of patients. Of the 18 patients evaluable for response, 4 (22%) had a partial response (2 confirmed), 7 (39%) had stable disease and 7(39%) developed progressive disease for a disease control rate of 61%. Survival analysis showed a median PFS of 2.7 months (1.4, N.E.) and OS of 7.7 months (5, N.E.). Clinical trial information: NCT03377023. The combination of nivolumab, ipilimumab and nintedanib was well tolerated and demonstrated antitumor activity despite tumor progression on prior ICI therapy. The ICI pretreated cohort has met the predefined response criteria for the 1st interim analysis ( > or = 2 responses) and will continue enrollment (with 20 additional patients) in the second stage.

P70.12 NTRK Gene Fusion in Advanced Non Small Cell Lung Cancer at Pham Ngoc Thach Hospital - Viet Nam

The NTRK gene fusion in lung cancer has been reported in more recent years, although this is a rare genetic alternation. We have conducted research for the following goals: 1. Investigation of the rate of NTRK gene fusion in advanced NSCLC patients. 2. Evaluate the ability to diagnose NTRK gen fusion by IHC compared to NGS. Retrospective research, cross-sectional descriptive statistics. General data: - Total number of research cases: 497 cases advanced NSCLC in 2020 - All researched cases have been diagnosed at hospital admission have not received specific treatment (chemotherapy, targeted therapy, immunotherapy ect.) - Male: 283 cases (56.94%) - Female: 214 cases (43.06%) - Average age: 58.35 ± 6.89 years - Patients with smoking: 207 cases (41.65%) - Number of cases with NTRK gene fusion, those have been diagnosed: IHC: 18 cases (3,62%) - NGS: 18 cases (3,62%) Histological distribution in NSCLC and associated expression of NTRK genes: - Adenocarcinoma: 386 cases [11 cases NTRK (+)] - Squamous cell carcinoma: 59 cases [3 cases NTRK (+)] - Adonosquamous carcinoma: 28 cases [1 case NTRK (+)] - Large cell carcinoma: 15 cases [2 cases NTRK (+)] - Carcinoma is not classified as NOS: 9 cases [1 case NTRK (+)] Distribution of NTRK gene fusion have expressioned on adenocarcinoma type: - Leipidic adenocarcinoma: 2 cases - Papillary adenocarcinoma: 1 case - Acinar adenocarcinoma: 4 cases - Micro-papillary adenocarcinoma: 1 case - Solid adenocarcinoma: 2 cases - Adenocarcinoma, poorly differentiated: 1 case Comments: - The rate of expression of the NTRK gene fusion in NSCLC at PNTH: 3.62% (Equivalent to other researches on the world (P = 0.0589 - 0.1564 > 0.05) - The rate of expression of NTRK gene fusion on adenocarcinoma is highest (11/18 cases # 61.11%), similar to other researches on the world (P = 0.0775 - 0.2513 > 0, 05) - Distribution of NTRK gene fusion on adenocarcinoma has differenced among histological types: acinar adenocarcinoma has the highest rate (4/11 cases # 36.36%) - Similarity between diagnosis with IHC & NGS: 100% (No false positives or false positives) Currently in NSCLC, the diagnostic NTRK gene fusion has many methods: IHC, FISH, RT-PCR, NGS in which NGS is the most supported technique due to detection of most NTRK lines. However, there are still difficulties in diagnosis due to many factors: professional experience, equipment, Test-Kit ect. IHC with specific markers shows high similarity to NGS. So in the future, can it be used this diagnostic method to indicate NTRK TKIs or not? Feasibility studies are still waiting for diagnostic tests and drugs to treat NTRK Gene Fusion.

P29.02 Early GLS Changes Detection After Chemoradiation in Locally Advanced NSCLC

Chemoradiation is the standard treatment in locally advanced NSCLC (LA-NSCLC) patients and thanks to recent combination with immunotherapy, median survival has reached unexpected improvements. In this new scenario, survivorship questions have become unmet needs, preventing toxicity a clear goal of the most current research. Cardiotoxicity is linked to thoracic irradiation with clinical manifestations such as pericardial disease, ischemic heart disease, nonischemic cardiomyopathy, valvular disease, conduction abnormalities, and arrhythmias.

P17.03 Sintilimab With Two Cycles Nab-Paclitaxel / Platinum as First Line Therapy for Advanced Squamous Non–Small-Cell Lung Cancer

Although immune checkpoint inhibitors (ICIs) in combination with chemotherapy has become the new stand of care in NSCLC, the optimal treatment cycles of chemotherapy is still debating. Chemotherapy is able to sensitize immune response in combination with ICIs via inducing tumor cell apoptosis and releasing neoantigen in initial combining cycles. In contrast, increasing cycles of chemotherapy might play negative roles of toxicity rather than synergetic effects. Therefore, this open-lable, multi-center, phase II study is to investigate the efficacy and safety of sintilimab in combination with short-course (two cycles) nab-paclitaxel / platinum in treatment naïve advanced squamous NSCLC patients.

P57.02 Integration of Systemic / Tumor PD-L1 as a Predictive Biomarker of Clinical Outcome in Advanced NSCLC Patients Treated With Anti-PD-(L)1 Agents

Tumor PD-L1 expression is a predictive biomarker for NSCLC patients (pts) receiving anti-PD-(L)1 agents. However, clinical benefit has been observed regardless of tumor PD-L1 expression, suggesting the existence of other PD-L1 sources. The aim of our study was to analyze whether integrating systemic and tumor PD-L1 is more predictive of outcome in advanced NSCLC pts receiving PD-(L)1 blockade agents. Pretreatment blood samples were collected to evaluate PD-L1 levels on circulating immune cells, platelets (PLTs), platelet microparticles (PMPs) and plasmatic concentrations of soluble PD-L1 (sPD-L1). Tumor PD-L1 status was assessed by immunohistochemistry. The percentages of circulating PD-L1+ leukocytes, PLTs, sPD-L1 levels and tumor PD-L1 expression were correlated with clinical outcome. 29 healthy donors and 119 advanced NSCLC pts treated with anti-PD-(L)1 were prospectively included. Median follow-up: 10.97 months [IQR: 6.06-21.87]. Median age of NSCLC patients was 65 (36-84), 78.1% were male and the most common histology was non-squamous (61.3%). Tumor PD-L1 expression (IHC 22C3 pharmDx) : <1% 30 pts (25.2%), 1-49% 35 (29.4%), ≥50% 37 (31.1%), not evaluable 17 (14.3%). PD-(L)1 inhibitors were given in 1st line in 37 pts (31.1%) and in ≥2nd line in 82 (68.9%), and given as monotherapy in 104 pts (87.4%), combination with chemotherapy in 11 pts (9.2%), or with other immunotherapy in 4 pts (3.4%) pts. Significantly longer progression free survival was observed in pts with higher percentage of PD-L1+ CD14+, PD-L1+ neutrophils, PD-L1+ PLTs and PD-L1+ PMPs and significantly longer overall survival was observed in pts with higher percentages of PD-L1+ CD14+ and high tumor PD-L1 expression (Table 1). Higher levels of integrated PD-L1 data of circulating and tumor PD-L1 results significantly stratified patients according to efficacy of PD-(L1) blockade agents (PFS: HR 0.29; 95% CI: 0.16-0.54, p<0.0001; OS: HR 0.28; 95% CI: 0.14-0.54, p=0.0002), even when tumor PD-L1 expression was excluded.Table 1PFSOSVariablesHR95% CIPHR95% CIP% PD-L1+ CD4+0.760.44-1.320.330.790.45-1.390.42% PD-L1+ CD8+0.690.41-1.160.160.810.47 – 1.390.45% PD-L1+ NK1.170.69-1.990.551.10.63 – 1.90.72% PD-L1+ CD14+0.360.22-0.58<0.0010.580.37- 0.930.02% PD-L1+ Neutrophils0.510.32-0.8<0.010.680.43–1.070.09% PD-L1+ PLTs0.480.26-0.880.020.970.51-1.960.93% PD-L1+ PMPs0.490.28-0.870.020.570.29-1.10.09pg/ml sPD-L11.260.81-1.970.291.240.78-1.970.34% TPS ≥50% vs <1% ≥50% vs 1-49%0.65 0.610.36-1.18 0.32 - 1.150.23 0.230.47 0.590.24-0.91 0.31-1.120.02 0.02 Open table in a new tab Our results suggest that the integration of circulating PD-L1+ leukocytes, PLT, PMPs and sPD-L1 and tumor PD-L1 expression could be helpful to decide the best treatment strategy in advanced NSCLC pts candidates for anti-PD-(L)1 agents.