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Juliann Dziubinski



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    P1.12 - Small Cell Lung Cancer/NET (Not CME Accredited Session) (ID 944)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.12-06a - Rovalpituzumab Tesirine Maintenance Therapy Following 1st Line Platinum‑Based Chemotherapy in Small Cell Lung Cancer (ID 13432)

      16:45 - 18:00  |  Author(s): Juliann Dziubinski

      • Abstract
      • Slides

      Background

      Small Cell Lung Cancer (SCLC) embodies 15-20% of lung cancers. Patients are staged with either limited or extensive disease (ED); the standard front-line treatment for the latter is chemotherapy with carbo- or cisplatin combined with etoposide or irinotecan. Response rates are high with limited duration. Recurrence may be attributable to chemo-resistant tumor initiating cells (TICs). Delta-like protein 3 (DLL3) is an inhibitory Notch receptor ligand identified as a novel target in SCLC TICs. DLL3 is highly expressed in SCLC but not normal tissue. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate composed of a DLL3-targeting IgG1 monoclonal antibody tethered to a DNA cross-linking toxin. Rova-T has shown activity in recurrent/relapsed ED SCLC patients1. Given DLL3 expression in TICs, exploration of Rova-T front-line maintenance strategies in ED SCLC is warranted. The postulated mechanism of action of Rova-T and its clinical activity indicate potential to improve progression-free and overall survival in this setting.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a Phase 3, randomized, double-blind, placebo-controlled, international study (NCT03033511, no patients enrolled yet as of 7 February 2017). Approximately 740 ED SCLC patients will be enrolled to include ~480 patients with high DLL3 expression. Eligibility: patients ≥ 18 years; histologically or cytologically confirmed ED SCLC with ongoing clinical benefit (complete/partial response or stable disease) after 4 cycles of 1st line platinum-based therapy; definitively treated CNS metastases allowed; > 3 but ≤ 9 wks between the administration of the last cycle of platinum-based chemotherapy and randomization; available tumor tissue for DLL3 expression testing; ECOG performance score 0-1. Patients will be randomly assigned 1:1 to receive 0.3 mg/kg Rova-T or placebo on Day 1 of each 6-wk cycle, omitting every 3rd cycle. Primary objectives: determine if Rova-T improves progression-free and overall survival. Secondary objectives: assess Rova-T antitumor activity by determining objective response rate, clinical benefit rate, duration of response, and changes in patient reported outcomes.

      1. Rudin et al., Lancet Oncol, 2016.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

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      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P1.12-06b - Rovalpituzumab Tesirine vs Topotecan in Patients with Advanced Small Cell Lung Cancer Following 1<sup>st</sup> Line Chemotherapy (ID 13438)

      16:45 - 18:00  |  Author(s): Juliann Dziubinski

      • Abstract
      • Slides

      Background

      Small cell lung cancer (SCLC) represents ~15% of lung cancers. Standard therapy most often consists of a platinum-based therapy + a second agent (etoposide). Initial response rates are high but not durable. Treatment for relapsed patients is limited, but includes topotecan. However, efficacy of topotecan is suboptimal and there is a high unmet need in this population. Delta-like protein 3 (DLL3) is an atypical Notch receptor family ligand identified as a target in SCLC and neuroendocrine carcinomas (NECs). DLL3 is highly expressed in SCLC and NECs but not normal tissue. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate composed of a DLL3-targeting IgG1 monoclonal antibody tethered to a toxic DNA crosslinker. Rova-T has antitumor activity in relapsed SCLC patients, and was well-tolerated1. Thus, we are investigating Rova-T vs topotecan as a 2nd line therapy in advanced SCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a Phase 3, randomized, open-label, multicenter study (NCT03061812) to assess efficacy, safety, and tolerability of Rova-T vs topotecan. Approximately 411 patients will be enrolled and randomized 2:1 between 2 arms. Arm A regimen: 0.3 mg/kg Rova-T intravenous (IV) on Day 1 + 8 mg dexamethasone orally, twice daily on Day -1, 1 and 2 of a 42-day cycle; administered for 2 cycles with up to 2 additional cycles permitted. Arm B: 1.5 mg/m2 topotecan (or per local label) IV on Days 1-5 of each 21-day cycle; administered until disease progression. Patient eligibility: ≥ 18 years; confirmed, advanced/metastatic SCLC with first disease progression following frontline standard therapy; DLL3-high tumor expression; ECOG 0-1; no prior exposure to a pyrrolobenzodiazepine-based drug or topotecan, irinotecan, or other topoisomerase I inhibitor. Efficacy endpoints include progression free survival, overall survival, objective response rate, duration of response, and patient-reported outcomes.

      1. Rudin et al., Lancet Oncol, 2016.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

      6f8b794f3246b0c1e1780bb4d4d5dc53

      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.