Virtual Library

Start Your Search

Zhang Bao



Author of

  • +

    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • +

      MA11.06 - A PII Study of Toripalimab, a PD-1 mAb, in Combination with Chemotherapy in EGFR+ Advanced NSCLC Patients Failed to Prior EGFR TKI Therapies (Now Available) (ID 1160)

      14:00 - 15:30  |  Author(s): Zhang Bao

      • Abstract
      • Presentation
      • Slides

      Background

      EGFR TKI is the standard 1st line therapy for the patients (pts) with advanced NSCLC harboring EGFR mutations. While PD-1 checkpoint blockade has become an integral component of disease management for EGFR wild type NSCLC pts at various settings, platinum-based chemotherapy is still the standard of care for EGFR mutated NSCLC pts who progress after EGFR targeting therapy. Early attempts to combine EGFR TKI with checkpoint blockade had resulted in exacerbated immune related toxicity in the lung. Here we aimed to prospectively evaluate toripalimab, a humanized PD-1 mAb approved for 2nd line treatment of melanoma, in combination with chemotherapy to treat EGFR mutated NSCLC pts after failure of EGFR targeting therapy.

      Method

      This is a phase II, multicenter, open-label, single-arm study for pts with EGFR activating mutations who have failed prior EGFR-TKI therapies without T790M mutation or failed osimertinib treatment. Pts were treated with 240mg or 360mg fixed dose toripalimab once every 3 weeks in combination with carboplatin and pemetrexed for up to 6 cycles, followed by toripalimab plus pemetrexed maintenance therapy until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) at week 12 as assessed by investigator per RECIST v1.1 once every 6 weeks. Secondary endpoints were safety, ORR, DOR, DCR, TTR, PFS, OS, PK and immunogenicity.

      Result

      f14_2_1_3_pub.png

      Forty pts were enrolled from Apr 25, 2018 to March 22, 2019 with 52.5% female pts and a median age of 57.5. 57.5% pts harbored EGFR exon19 deletion while 42.5% pts had exon21 L858R mutation. Only 1 pt had T790M mutation who progressed after osimertinib treatment. In ITT population, 13 confirmed partial response (PR) and 22 stable disease (SD) were observed at week 12 for a 32.5% ORR. As of Jul 25 2019, among 40 pts, 20 confirmed PR and 15 SD were observed for a 50% ORR (95% CI, 33.8% to 66.2%) and an 87.5% DCR (95% CI, 73.2% to 95.8%). Median progression free survival (PFS) was 7.0 months, and median duration of response (DOR) was 7.0 months. Treatment emergent adverse events (TEAE) occurred in 39 (97.5%) of the pts, grade 3 or higher events occurred in 25 (62.5%) of pts including two deaths. Most common AE included leukopenia, neutropenia, thrombocytopenia, anemia, nausea, and loss of appetite. Treatment discontinuation due to AE occurred in 4 (10%) of the pts.

      Conclusion

      Anti-PD-1 mAb, toripalimab in combination with carboplatin and pemetrexed has shown a promising anti-tumor efficacy with a tolerable safety profile for advanced NSCLC patients with EGFR mutated who progressed after EGFR TKI therapies. Pts will be continuously monitored for safety and efficacy readouts (DOR, PFS and OS). A phase III registration study will be initiated in May 2019.

      (Clinical trial information: NCT03513666)

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.01-106 - Clinical Features and Tumor Immune Microenvironment Related to Acquired Resistance to EGFR-TKI in NSCLC Patients with EGFR Mutation (ID 2343)

      09:45 - 18:00  |  Author(s): Zhang Bao

      • Abstract

      Background

      First generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide significant clinical benefit in advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, patients with initial response to EGFR-TKI ultimately develop acquired resistance to EGFR-TKI treatment, which approximately 50% resistant patients develop second EGFR T790M mutation. New treatment strategy for NSCLC patients harboring EGFR T790M mutation has been available. For those EGFR T790M negative patients, chemotherapy is currently the standard treatment. However, the efficacy of immunotherapy in EGFR T790M mutation NSCLC patients is unknown. Our study focused on the relationship between the clinical features and EGFR T790M mutation status, and the tumor immune microenvironment change before and after acquired resistance to EGFR-TKI in NSCLC patients with EGFR mutation.

      Method

      In this study, we retrospectively evaluated 89 patients with EGFR mutation who received first generation EGFR-TKIs treatment at the First Affiliated Hospital of Zhejiang University between February 2012 and July 2018. All patients were performed second biopsy after acquired resistance to EGFR-TKI. EGFR T790M mutation, epithelial-mesenchymal transition (EMT) and tumor-infiltrating CD4 and CD8 lymphocytes (TILs) in 13 patients with paired biopsy specimens before and after resistance to EGFR-TKI were measured by next generation sequencing (NGS) and immunohistochemistry analyses respectively.

      Result

      Among the 89 eligible patients, EGFR T790M mutation rate was 59.6% (53/89). EGFR T790M mutation was not related with age, gender, smoking status, tumor stage, performance status, but related to the initial EGFR mutation type (EGFR exon 19 deletion or exon 21 L858R mutation). Patients with EGFR exon 19 deletion had significantly higher T790M mutation rate than that with exon 21 L858R mutation (p=0.025). Interestingly, among 11 patients with family cancer history, 10 patients acquired T790M mutation. Furthermore, patients with T790M mutation had longer progression-free survival (PFS) compared to T790M-negative patients (75.5% vs 63.9%, P<0.05). In the small cohort of 13 patients, 6 patients developed EMT after acquired resistance. TILs according to the CD4+ and CD8+ lymphocyte density were not significantly changed in all 13 patients before and after acquired resistance.

      Conclusion

      Our findings indicate that patients with EGFR exon 19 deletion、longer PFS or family cancer history may have higher possibility to develop second EGFR T790M mutation after resistance to EGFR-TKI treatment. The incidence of EMT was higher than we expected, providing further research and clinical treatment ideas. There is no change in TILs after resistance to EGFR-TKI in patients with or without EGFR T790M mutation, but this need further study due to the limited samples in this study.

    • +

      P1.01-36 - Clinical Potential of Tissue Tumor Mutational Burden (tTMB) and Blood TMB (bTMB) as a Biomarker in Non-Small Cell Lung Cancer (ID 2045)

      09:45 - 18:00  |  Author(s): Zhang Bao

      • Abstract
      • Slides

      Background

      Higher tissue TMB (tTMB) or blood TMB (bTMB) levels are associated with better response of immunotherapy in patients with non-small cell lung cancer (NSCLC). The clinical utility of bTMB and tTMB for clinical indications remain to be determined.

      Method

      Comprehensive genomic profiling were performed on 28 paired tissue and plasma samples using 520-gene panel, which has been validated to accurately reflect the actual tTMB and bTMB using in-house validation. The max allelic fraction (max.AF) of 5% in tissue and 0.5% in plasma were defined as the detection limit for TMB assessment, and samples with max.AF < 5% (n=1) in tissue and 0.5% in plasma (n=6) were excluded. Union-TMB represents the union of tTMB and bTMB, and union-TMB-class-10 denotes union-TMB of 10 is used as the cutoff for grouping.

      Result

      Correlation analysis revealed that bTMB and tTMB diaplayed significant consistency with each other (R2=0.953). Next, associations of clinical characteristics and TMB status were analyzed. Older patients were significantly associated with higher tTMB (p=0.009) than younger ones, but slightly correlated with TMB-max (p=0.055) and TMB-union (p=0.079). We also found that male patients more commonly had higher tTMB (p=0.001), bTMB (p=0.011), max-TMB (p<0.001), union-TMB (p<0.001) and union-TMB-class-10 (p=0.018) than female ones with statistical significance, while smokers usually had higher tTMB (p=0.003), max-TMB (p=0.011), union-TMB (p=0.004) and union-TMB-class-10 (p=0.044) than non-smokers. Next, the correlation between TMB and clinical response were investigated in 19 patients who received nivolumab treatment. We found patients who had partial response to nivolumab commonly had higher bTMB than those experienced stable disease or progression (p=0.076); patients with bTMB>=10 or bTMB>=16 achieved higher objective response rate (ORR) than that with bTMB<10 (42.9% vs 0.0%) or bTMB<16 (66.7% vs 10.0%); patients with squamous cell carcinoma achieved significantly favorable progression-free survival than those with adenocarcinoma (p=0.019).

      Conclusion

      We revealed that tTMB and bTMB were strongly correlated with each other for TMB assessment. Higher tTMB was strongly correlated with smokers and males compared with non-smokers and females. Higher bTMB predicted better response and ORR to nivolumab, indicating that bTMB could function as a biomarker for prognosis prediction. Prospective studies are necessary to investigate the clinical implications of tTMB and bTMB in a larger cohort of patients.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.