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T. Csoszi
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-096 - Randomized, Double-Blind, Placebo-Controlled Trial of Evofosfamide (TH-302) in Combination with Pemetrexed in Advanced ns-NSCLC (ID 659)
09:30 - 17:00 | Author(s): T. Csoszi
- Abstract
Background:
Tumor hypoxia is associated with chemo- and radioresistance and is a prevalent characteristic in tumors of patients with non-small cell lung cancer (NSCLC). Evofosfamide (previously known as TH-302) is a hypoxia-activated prodrug designed to release the bis-alkylating DNA crosslinker bromo-isophosphoramide mustard (Br-IPM) when reduced in severe hypoxia. In a Phase 1/2 study (NCT00743379) that included a single arm evofosfamide in combination with pemetrexed in 18 patients with relapsed/refractory non-squamous NSCLC, median PFS was 7.0 months and median OS was 14.9 months. Response in 15 evaluable patients: 6 partial responses (4 confirmed), 6 stable disease and 3 progressive disease. The most common adverse events were fatigue, anemia, stomatitis and nausea.
Methods:
An international, multicenter, randomized, double-blind, placebo-controlled trial was initiated to evaluate evofosfamide in combination with pemetrexed versus placebo and pemetrexed as a potential second-line treatment for patients with non-squamous NSCLC (NCT02093962). Approximately 440 patients will be enrolled with histologically confirmed stage IIIB or IV NSCLC with non-squamous histology, measurable disease according to RECIST 1.1, and ECOG performance status 0-1. Eligible patients have recurrent or progressive disease after one prior platinum-based non-pemetrexed chemotherapy treatment for advanced disease with or without maintenance. EGFR-activating and ALK rearrangements status must be known, and if identified, patients must have received a targeted kinase inhibitor. Evofosfamide (400 mg/m[2]) or matched placebo is administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle. Pemetrexed (500 mg/m[2]) is administered by IV infusion 2 to 4 hours after evofosfamide administration on Day 1. Overall survival (OS) is the primary endpoint; secondary endpoints include safety, progression-free survival and RECIST response rate. The study design has 85% power to detect a 40% improvement in OS with a one-sided alpha of 0.025. The first patient was enrolled in June 2014; recruitment is ongoing.
Results:
not applicable
Conclusion:
not applicable
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P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.07-010 - Alisertib (MLN8237)+Paclitaxel versus Placebo+Paclitaxel for Relapsed SCLC (ID 1158)
09:30 - 17:00 | Author(s): T. Csoszi
- Abstract
Background:
Small cell lung cancer (SCLC) is an aggressive malignant disease comprising approximately 14% of all lung cancers, with approximately 31,000 new diagnoses each year in the USA. SCLC has a very poor prognosis, particularly in patients presenting with extensive stage disease. Platinum-based combinations are standard first-line therapy for SCLC; however, relapse is almost universal (≥85%) and patients require further treatment in subsequent lines. Effective new targeted therapies are needed to improve the poor outcomes observed in SCLC. Alisertib is an investigational, orally available, selective inhibitor of Aurora A kinase. Alisertib has shown single-agent antitumor activity in preclinical in vivo models of SCLC and has demonstrated synergism with paclitaxel in this setting. Single-agent alisertib has demonstrated promising efficacy in patients with relapsed/refractory SCLC (Melichar B, et al. Lancet Oncol 2015;16[4]:395–405). Further, phase 1 and 2 evaluation of alisertib+paclitaxel in patients with relapsed ovarian cancer and breast cancer has suggested the antitumor activity of this combination (Falchook G, et al. Int J Gynecol Cancer 2013;23[8] Suppl_1:abstract; Coleman R, et al. Ann Oncol 2014;25[Suppl_4]:abstract 876O). Here we describe the design and objectives of an ongoing phase 2, randomized, double-blind, placebo-controlled study of alisertib+paclitaxel versus placebo+paclitaxel in patients with relapsed SCLC and previously treated with only one line of platinum-based therapy (NCT02038647).
Methods:
Approximately 166 adult patients with relapsed SCLC after standard first-line platinum-based therapy, measurable disease by RECIST v1.1, and Eastern Cooperative Oncology Group performance status 0 or 1 will be enrolled at approximately 80 sites in the USA and Europe. Patients will be randomized 1:1 (stratified by type of relapse [sensitive vs resistant/refractory] and presence of brain metastases) to receive 28-day cycles of either alisertib 40 mg or matched placebo PO twice daily on days 1−3, 8−10, and 15−17, plus paclitaxel 60 or 80 mg/m[2 ]IV, respectively, on days 1, 8, and 15, until disease progression or unacceptable toxicity. The primary endpoint of the trial is progression-free survival (PFS). Assuming a hazard ratio of 0.6 for PFS, a total of 138 progression/death events will be required to provide 85% power (two-sided alpha=0.05). Secondary endpoints include: overall and complete response rates; disease control rate; duration of response; overall survival; safety (NCI-CTCAE v4.03); alisertib pharmacokinetics; and symptom-related endpoints (symptom score, time to symptom relief, time to symptom progression). Evaluation of candidate biomarkers in tumor tissue specimens and in circulating tumor cells (CTC)/circulating tumor DNA, change from baseline in CTC numbers, and health-related quality of life (EORTC QLQ-C30/QLQ-LC13 instruments) are exploratory endpoints. As of 10 April 2015, there are 60 sites open in 6 countries with 90 patients randomized. The study continues to enroll patients.
Results:
not applicable
Conclusion:
not applicable
