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Charles M. Rudin



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    ES26 - Future Horizons in the Management of Small Cell Lung Cancer (ID 225)

    • Event: WCLC 2020
    • Type: Educational Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
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      ES26.02 - Antibody Drug Conjugates and T-cell Engagers (ID 4064)

      14:15 - 15:15  |  Presenting Author(s): Charles M. Rudin

      • Abstract

      Abstract not provided

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    FP03 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) (ID 151)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • 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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      FP03.03 - Clinical Activity of BMS-986012, an Anti–Fucosyl-GM1 Monoclonal Antibody, Plus Nivolumab in Small Cell Lung Cancer (ID 3396)

      00:00 - 00:00  |  Author(s): Charles M. Rudin

      • Abstract

      Introduction

      In patients with extensive-stage small cell lung cancer (ES-SCLC), the addition of an anti–PD-L1 regimen to chemotherapy demonstrated limited benefit, with an increase in survival by 2 months (Horn et al. N Engl J Med. 2018;379:2220–2229). Therefore, future prospects for better outcomes in SCLC lie in novel medicines and new treatment combinations. Fucosyl-GM1 is a monosialoganglioside expressed in 50%–70% of SCLC with limited expression in normal tissues (Brezicka et al. APMIS. 1991;99:797–802; Brezicka et al. Tumour Biol. 1992;13:308–315). BMS-986012 is a nonfucosylated, fully human monoclonal antibody with high binding specificity for fucosyl-GM1 engineered to enhance antibody-dependent, cell-mediated cytotoxicity (Ponath et al. Clin Cancer Res. 2018;24:5178–5189). We previously reported that the combination of BMS-986012 and nivolumab in patients with relapsed/refractory SCLC was well tolerated and demonstrated preliminary antitumor activity (Chu et al. Ann Oncol. 2017;28(suppl 5). Abstract 1528PD). Here, we report updated safety and antitumor activity results from the phase 1/2 trial of the combination of BMS-986012 and nivolumab in patients with relapsed/refractory SCLC (NCT02247349).

      Methods

      Patients with relapsed/refractory SCLC who had not received prior checkpoint inhibitor (CPI) therapy received BMS-986012 400 or 1000 mg with nivolumab 360 mg intravenously every 3 weeks. The primary endpoint was safety. Secondary endpoints included investigator-assessed objective response rate (ORR), median duration of response (mDOR), median progression-free survival (mPFS), and pharmacokinetics. Median overall survival (mOS) was an exploratory endpoint.

      Results

      As of July 22, 2020, 29 patients received BMS-986012 (400 mg, n=21; 1000 mg, n=8) with nivolumab, with a follow-up of 18.6 months (range, 0.6–41.1 months). Median age of patients was 65 years (range, 46–79 years) and 52% were male; ECOG performance status was 0 (38%) or 1 (62%). The combination was well tolerated, with manageable adverse effects. The most common all-grade/grade ≥3 treatment-related adverse events were pruritus (93%/21%), fatigue (28%/0%), dry skin (28%/0%), and hypothyroidism (17%/0%). In most patients, pruritus diminished over time and was managed with antihistamines and low-dose corticosteroids. Confirmed ORR with BMS-986012 plus nivolumab was 38% (CR, n=1 [3%]; PR, n=10 [35%]), with 3 additional patients (10%) having SD, for an overall disease control rate of 48%. At data cutoff, mDOR was 26.4 months (95% CI, 4.4 months–NR); 4 patients were still on therapy. mPFS was 2.1 months (95% CI, 1.4–9.9 months) and mOS was 18.7 months (95% CI, 8.2 months–NR). No differences in response were noted between platinum-sensitive and refractory populations.

      Conclusion

      The results presented here suggest that BMS-986012 plus nivolumab is a promising therapeutic combination for the treatment of patients with relapsed/refractory SCLC not previously treated with CPI therapy, irrespective of whether their cancers were platinum sensitive or refractory. The safety profile was manageable, and although based on a small number of patients, responses were clinically meaningful and durable. These updated data warrant further investigation of this combination in patients with SCLC.

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    IS02 - Industry Symposium Sponsored by AstraZeneca: Evolving the Role of Immunotherapy in Lung Cancer: ES-SCLC and Unresectable Stage III NSCLC (ID 278)

    • Event: WCLC 2020
    • Type: Industry Symposium
    • Track:
    • Presentations: 1
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      IS02.05 - Emerging Biomarkers in SCLC (ID 4313)

      10:30 - 11:30  |  Presenting Author(s): Charles M. Rudin

      • Abstract

      Abstract not provided

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    P47 - Small Cell Lung Cancer/NET - Biology / Translational (ID 234)

    • 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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      P47.06 - Delta-Radiomics Features for Assessment of Individualized Therapeutic Response in Small Cell Lung Cancer – A Pilot Study (ID 3340)

      00:00 - 00:00  |  Author(s): Charles M. Rudin

      • Abstract

      Introduction

      The difficulty of assessment of treatment response by current RECIST (Response Evaluation Criteria in Solid Tumors) criteria, limited by interobserver agreement and tumoral heterogeneity, may hinder personalized-medicine strategies in small cell lung cancer (SCLC). Our purpose is to evaluate computed tomography (CT) radiomic features before and after platinum-based chemotherapy in SCLC patients and to investigate how therapy-induced changes in these features, called delta-radiomics (DR) features, are related to treatment response as assessed by RECIST v 1.1.

      Methods

      18 patients with limited (2/18) or extensive (16/18) stage SCLC were retrospectively enrolled and CT scans immediately before and after platinum-based chemotherapy were analyzed. Patients were dichotomized into a group of responders [R] (partial response) and nonresponders [NR] groups (meaning stable or progressive disease) according RECIST v 1.1 criteria. Six patients were excluded for lack of standardization (acquisition protocol, intravenous contrast or image quality) between scans. Tumors were manually segmented (ITK SNAP v 3.8) and 101 radiomics features were extracted from both pre- and post-treatment images. A delta-radiomics signature was constructed using LASSO regression, a support vector machine and 5-fold cross-validation algorithms. ROC analysis to evaluate diagnostic accuracy for R vs NR differentiation was performed with a DeLong confidence interval for Area Under Curve (AUC).

      Results

      The delta-radiomics signature showed higher AUC than single-CT based radiomics signatures. Significant differences were noted for 12 radiomics features, between R and NR groups (P < 0.05). After LASSO regression 3 parameters were advanced to modelling. The accuracy of the final delta-radiomics model was 92%, sensitivity 86%, specificity 100.0%, positive predictive value 100%, negative predictive value 83.3% and area under ROC curve of 0.89.

      Conclusion

      Preliminary results showed a potential role of a delta-radiomics CT model in the individualized assessment of platinum-based chemotherapy response in SCLC. Larger sample studies are required to validate the reliability and reproducibility of our proposed radiomics model.