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A. Ko
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-077 - First-Line Nivolumab + Nab-Paclitaxel + Carboplatin (C) in Advanced NSCLC (ID 1565)
09:30 - 09:30 | Author(s): A. Ko
- Abstract
Background:
Nivolumab, an anti-PD-1 inhibitor, has demonstrated anti-tumor activity in several solid tumors and is approved for unresectable/metastatic melanoma and disease progression following ipilimumab, and if BRAF V600 mutation positive, a BRAF inhibitor; and for metastatic squamous NSCLC in patients with progression on/after platinum-based chemotherapy. Combining a taxane, which can act as a cytotoxic and an immunomodulator, with an immune checkpoint inhibitor has demonstrated improved outcomes over chemotherapy alone in NSCLC. First-line nivolumab and solvent-based paclitaxel plus C (sb-P/C) resulted in a 43% overall response rate and a median progression-free survival of 31 weeks in an interim analyses from a phase I trial in patients with advanced NSCLC (Antonia et al. Presented at ASCO 2014 [Abstract 8113]). nab-Paclitaxel (nab-P) based therapy has demonstrated improved efficacy over standard treatment in pancreatic and breast cancers, and nab-P plus carboplatin (nab-P/C) significantly improved the primary endpoint (ORR) vs sb-P/C in a phase III trial of patients with advanced NSCLC (Socinski et al. J Clin Oncol. 2012;30:2055-2062) and does not requires immunosuppressive premedication. This phase I, open-label, 6-arm, multicenter trial, will evaluate safety of nivolumab with nab-P in 3 cancer types: advanced NSCLC (+ C), advanced pancreatic cancer (± gemcitabine), and metastatic breast cancer; 2 arms in each disease. The study design for the NSCLC portion is described below.
Methods:
Eligibility criteria include histologically/cytologically confirmed stage IIIB/IV NSCLC, no prior chemotherapy for metastatic disease, prior adjuvant chemotherapy allowed providing completion >12 months before study entry, ECOG PS 0-1, adequate organ function, and preexisting peripheral neuropathy grade <2. NSCLC patients will be treated in 2 arms: 4 cycles of nab-P 100 mg/m[2] on days 1, 8, and 15 plus C AUC 6 on day 1 of a 21 day cycle with nivolumab 5 mg/kg on day 15 starting at cycle 1 or the same nab-P/C regimen with nivolumab 5 mg/kg on day 15 starting at cycle 3. In both arms, nivolumab monotherapy will begin at cycle 5. Part 1 will assess the dose-limiting toxicities (DLTs) of the nivolumab dose with nab-P/C (≈ 6 patients/arm). If deemed safe, the treatment arms may be expanded using the recommended part 2 dose with an additional ≈ 14 patients/arm (total of 20 nivolumab-treated patients/arm) to further assess safety and tolerability as well as anti-tumor activity. Patients will be allowed to continue nivolumab treatment beyond RECIST 1.1 disease progression (physician discretion). ClinicalTrials.gov number NCT02309177. Figure 1 .
Results:
Not applicable
Conclusion:
Not applicable
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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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P2.01-099 - nab-Paclitaxel as Maintenance Therapy in Patients with Squamous Cell NSCLC (ABOUND.sqm) (ID 3122)
09:30 - 09:30 | Author(s): A. Ko
- Abstract
Background:
Patients with squamous cell (SCC) non-small cell lung cancer (NSCLC) may be at risk of poorer outcomes and have fewer treatment options than those with other histologies. Furthermore, no randomized studies have demonstrated the benefit of maintenance therapy in these patients. In a phase III trial, first-line treatment with nab-paclitaxel plus carboplatin (nab-P/C) demonstrated a 68% improvement in the overall response rate (ORR; 41% vs 24%; P < 0.001) and a trend toward improved overall survival (OS; median, 10.7 vs 9.5 months; HR 0.890; P = 0.310) compared with solvent-based paclitaxel plus C in a subset of patients with advanced SCC NSCLC (Socinski et al. Ann Oncol. 2013;24:2390-2396). An exploratory analysis of the phase III trial demonstrated that therapy with nab-P/C beyond 4 cycles of first-line treatment was effective in the subset of patients with SCC NSCLC who did not progress (from the time of randomization, median progression-free survival [PFS] and OS were 6.8 and 13.8 months, respectively), and no new safety signals were noted (Socinski et al. IASLC 2013 [abstract 3438]). In the open-label, multicenter phase III ABOUND.sqm trial, the efficacy and safety of nab-P maintenance therapy after nab-P/C induction therapy will be evaluated in patients with advanced SCC NSCLC.
Methods:
During the induction part of the study, approximately 540 patients will be treated with 4 cycles of nab-P 100 mg/m[2] intravenously (IV; 30-minute infusion) on days 1, 8, and 15 plus IV C AUC 6 on day 1 every 21 days. Patients with a complete response (CR), a partial response (PR), or stable disease (SD) will be eligible for maintenance. In the maintenance part of the study, approximately 260 patients will be randomized 2:1 to nab-P 100 mg/m[2] on days 1 and 8 every 21 days plus best supportive care (BSC) or BSC alone until disease progression. Patients will be stratified by disease stage (IIIB vs IV), response to induction therapy (CR/PR vs SD), and ECOG performance status at the end of induction (0 vs 1). Key eligibility criteria include histologically or cytologically confirmed stage IIIB/IV SCC NSCLC, no prior chemotherapy for metastatic disease, ECOG performance status ≤ 1, adequate organ function, no active brain metastases, and preexisting peripheral neuropathy grade < 2. ClinicalTrials.gov identifier NCT02027428.Key Endpoints Primary PFS from randomization into the maintenance part of the study Secondary Safety OS from randomization into the maintenance part of the study ORR during the induction and maintenance parts of the study Exploratory Correlation between pretreatment tumor characteristics and response to treatment Association between changes in tumor characteristics and acquisition of resistance to therapy at the time of treatment failure during maintenance Correlation between genetic polymorphisms and treatment efficacy and/or toxicity Healthcare resource utilization during the maintenance part of the study Changes in quality of life
Results:
Not applicable.
Conclusion:
Not applicable.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-089 - Nab-Paclitaxel with or without CC-486 as Second-Line Therapy for NSCLC (ABOUND.2L) (ID 719)
09:30 - 09:30 | Author(s): A. Ko
- Abstract
Background:
Many patients with advanced non-small cell lung cancer (NSCLC) will experience disease progression during first-line chemotherapy. Effective and well-tolerated second-line treatment options for this patient population are limited. In a multicenter phase III trial, first-line treatment with nab-paclitaxel plus carboplatin (nab-P/C) significantly improved the primary endpoint of overall response rate (ORR) compared with solvent-based paclitaxel plus C in patients with advanced NSCLC (33% vs 25%; P = 0.005; Socinski et al. J Clin Oncol. 2012;30:2055-2062). nab-P combined with CC-486, an oral formulation of azacitidine, resulted in promising outcomes in a phase I trial of patients with relapsed/refractory solid tumors (LoRusso et al. Mol Cancer Ther. 2013;12(11 Suppl):Abstract A120). In the open-label, multicenter phase II ABOUND.2L trial, the safety and efficacy of nab-P with or without CC-486 will be evaluated in the second-line treatment of patients with advanced nonsquamous NSCLC.
Methods:
Approximately 160 patients who have received 1 platinum-containing chemotherapy regimen for treatment of advanced disease will be randomized 1:1 to CC-486 200 mg/day on days 1 to 14 every 21 days plus nab-P 100 mg/m[2] intravenously (IV; 30-minute infusion) on days 8 and 15 every 21 days or nab-P 100 mg/m[2] IV (30-minute infusion) on days 1 and 8 every 21 days. Key eligibility criteria include histologically or cytologically confirmed advanced nonsquamous NSCLC, ECOG performance status ≤ 1, adequate organ function, no active brain metastases, no prior taxane therapy, no known EGFR mutation or EML4-ALK translocation, and peripheral neuropathy grade < 2. Randomization will be stratified by ECOG performance status (0 vs 1), sex, and smoking status (yes vs no). ClinicalTrials.gov identifier NCT02250326.Key Endpoints
Primary -Progression-free Survival Secondary -Disease control rate -Overall Survival -ORR -Safety Exploratory -Changes in quality of life -Healthcare resource utilization throughout the study -Correlation between pretreatment tumor characteristics and response to treatment
Results:
Not applicable
Conclusion:
Not applicable
