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M. Shah
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P1.04 - Clinical Design, Statistics and Clinical Trials (ID 690)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.04-006 - Rovalpituzumab Tesirine vs Topotecan in Patients with Advanced Small Cell Lung Cancer Following 1<sup>st</sup> Line Chemotherapy (ID 8393)
09:30 - 09:30 | Author(s): M. Shah
- Abstract
Background:
Small cell lung cancer (SCLC) represents ~15% of lung cancers. Patients (pts) are staged with limited or extensive stage disease (ES). ES standard therapy consists of a platinum-based therapy + a second agent (etoposide). Initial response rates are high but not durable. Treatment for relapsed pts 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 ES SCLC pts, and was well-tolerated[1]. Thus, we are investigating Rova-T vs topotecan as a 2[nd] line therapy in advanced SCLC.
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 pts 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/m[2] topotecan (or per local label) IV on Days 1-5 of each 21-day cycle; administered until disease progression. Pt 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. Primary objectives: to determine if Rova-T improves objective response rate and overall survival vs topotecan. Secondary objectives: to assess if Rova-T improves progression-free survival vs topotecan; to compare duration of objective response between arms; and to assess effect on patient-reported outcomes. 1. Rudin et al., Lancet Oncol, 2016.
Result:
Section not applicable
Conclusion:
Section not applicable
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P1.04-007 - Rovalpituzumab Tesirine Maintenance Therapy Following 1st Line Platinum-Based Chemotherapy Small Cell Lung Cancer (ID 8396)
09:30 - 09:30 | Author(s): M. Shah
- Abstract
Background:
SCLC embodies 15-20% of lung cancers. Patients (pts) are staged with either limited or extensive disease; 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 patients[1]. 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.
Method:
This is a Phase 3, randomized, double-blind, placebo-controlled, international study (NCT03033511, no pts enrolled yet as of 7 February 2017). Approximately 740 ED SCLC pts will be enrolled to include ~480 pts with high DLL3 expression. Eligibility: pts ≥ 18 years; histologically or cytologically confirmed ED SCLC with ongoing clinical benefit (complete/partial response or stable disease) after 4 cycles of 1[st] 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. Pts 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 3[rd] 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 pt reported outcomes. 1. Rudin et al., Lancet Oncol, 2016.
Result:
Section not applicable
Conclusion:
Section not applicable
