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R.G. Martins
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MA09 - Immunotherapy Combinations (ID 390)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:M. Sebastian, E.B. Garon
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 2
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MA09.02 - Pembrolizumab + Carboplatin and Pemetrexed as 1st-Line Therapy for Advanced Non–Small Cell Lung Cancer: KEYNOTE-021 Cohort G (ID 5787)
14:26 - 14:32 | Author(s): R.G. Martins
- Abstract
- Presentation
Background:
Platinum doublet chemotherapy ± bevacizumab is standard first-line therapy for patients with advanced non–small cell lung cancer (NSCLC) without genetic aberrations. Single-agent pembrolizumab exhibits robust antitumor activity in PD-L1–positive advanced NSCLC. Cohort G of the multicenter, open-label, phase 1/2 multicohort KEYNOTE-021 study (ClinicalTrials.gov, NCT02039674) evaluated the efficacy and safety of pembrolizumab + carboplatin and pemetrexed compared with carboplatin and pemetrexed in patients with treatment-naive advanced nonsquamous NSCLC with any PD-L1 expression.
Methods:
Cohort G enrollment criteria included patients with stage IIIB/IV nonsquamous NSCLC, no activating EGFR mutation or ALK translocation, no prior systemic therapy, measurable disease, ECOG performance status 0-1, and adequate tumor sample for assessment of PD-L1 status, regardless of PD-L1 expression. Patients were randomized 1:1 to 4 cycles of pembrolizumab 200 mg Q3W + carboplatin AUC 5 (5 mg/mL/min) + pemetrexed 500 mg/m[2] Q3W or carboplatin AUC 5 (5 mg/mL/min) + pemetrexed 500 mg/m[2] Q3W alone, followed by maintenance pemetrexed ± pembrolizumab. Pembrolizumab was given for ≤35 cycles. Randomization was stratified by PD-L1 expression (positive [tumor proportion score, or TPS, ≥1%] vs negative [TPS <1%]). Crossover to pembrolizumab monotherapy was allowed for eligible patients who experienced disease progression (RECIST v1.1) on chemotherapy. Response was assessed by central imaging vendor review every 6 weeks for first 18 weeks, every 9 weeks through year 1, and every 12 weeks in year 2. The primary end point was objective response rate (ORR); secondary end points included progression-free survival (PFS), duration of response, and overall survival (OS). Comparison between arms was assessed using the stratified Miettinen and Nurminen method (ORR) and stratified log-rank test (PFS, OS).
Results:
As of January 2016, 123 patients (60 in the pembrolizumab + chemotherapy arm, 63 in the chemotherapy arm) had been enrolled in cohort G. Data on ORR, duration of response, safety, and preliminary PFS and OS results will be available by August 2016.
Conclusion:
The conclusion will be updated at the late-breaking submission stage.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-001 - Phase 1 Dose Escalation of PF-06747775 (EGFR-T790M Inhibitor) in Patients with Advanced EGFRm (Del 19 or L858R+/-T790M) NSCLC (ID 4747)
14:30 - 14:30 | Author(s): R.G. Martins
- Abstract
Background:
PF-06747775 (PF-7775) is a highly potent, selective third generation irreversible EGFR-TKI, effective against EGFR-TKI sensitizing and resistance (T790M) mutations in NSCLC cell lines; IC50s between 3-12 nM and 26X greater selectivity toward mutant vs. wild-type (WT)EGFR. This is the first report from an ongoing phase I, first in human multicenter study (NCT02349633) of PF-7775 in patients with metastatic EGFRm+ NSCLC.
Methods:
EGFRm+ NSCLC pts, with acquired resistance to EGFR-TKIs enrolled into dose escalation cohorts of PF-7775, orally once daily, beginning at 25 mg. Stable brain metastases were allowed. All pts were assessed for pharmacokinetics (PK), response to therapy, and adverse events (AEs). Prospective central T790M testing was optional for dose escalation cohorts, but is required in subsequent expansion cohorts. Plasma samples were collected from all patients for ctDNA analysis of EGFR mutations.
Results:
Dose escalation is complete. 26 patients enrolled in 7 dose levels (25-600 mg): 58% female, mean age 63.5 years, Asian/Caucasian 61%/34%, 14/25 T790M+. Dosing reached 600 mg and then was expanded at a lower dose for better long term tolerability. RECIST responses were observed at all dose levels. BOR is PR 11(42.3%; 5 T790M+), stable disease 6(23.1%; 4 T790M+), PD 2(7.7%: 1 T790M+), symptomatic deterioration 1(3.8%; 1 T790M+), and indeterminate 6(23.1%; 3 T790M+). The AE profile is very favorable as predicted from the large WT margin. No DLTs were observed. Grade 3 AEs were noted at > 150 mg (diarrhea {n=4, 15.4%} and skin toxicities {n=8, 30.8%}). Figure 1. Best Change from Baseline in Tumor Size (%) Figure 1 PK were generally dose-proportional at doses of 25-600 mg, with a median apparent t~1/2~ of 6 h (range 4-30).
Conclusion:
PF-7775 has demonstrated early signals of clinical activity and is well tolerated in EGFRm+ NSCLC pts with acquired resistance to EGFR-TKIs.
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P3.02b-061 - A Phase II Study of Nab-Paclitaxel (Nab-P) in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with EGFR Mutations (ID 4337)
14:30 - 14:30 | Author(s): R.G. Martins
- Abstract
Background:
Patients with NSCLC harboring a sensitizing EGFR mutation have effective targeted therapy options initially but most patients eventually need to receive cytotoxic chemotherapy. We previously reported our institutional experience with taxane based therapy in this patient population and this provided the rationale for the currently ongoing phase II study (NCT01620190).
Methods:
Patients with EGFR mutation positive NSCLC who were refractory to tyrosine kinase inhibitor (TKI) therapy and chemotherapy naive received nab-P at 125mg/m2 on days 1, 8 and 15 in a 28-day cycle. The primary endpoint was response rate which was assessed using RECIST v1.1.
Results:
As of data cut-off of March 14 2016, 22 patients were enrolled and received therapy (19 evaluable, 2 not yet evaluable, 1 patient excluded due to not being eligible). Median age was 65 (range 54-77), 75% of patients were women, 40% did not have a smoking history and majority (65%) of patients had an ECOG performance status of 1. Tumor histology consisted mostly of adenocarcinoma (90%); 55% of patients harbored exon 21 L858R and 45% harbored exon deletion 19 mutations. Confirmed partial response was documented in 8 of 19 (42%) patients with a median duration of response of 4.3 months (range 3.3-9.5) and stable disease was documented in 4 of 19 (21%) patients with a disease control rate of 63%. Median progression free survival was 4.4 months (95% CI 1.8-5.5 months). The most common grade 3 treatment-related adverse events (AE) were peripheral neuropathy (10%), fatigue (10%) and neutropenia (15%). There were no treatment-related grade 4 AEs.
Conclusion:
Single agent nab-P has promising activity in patients with EGFR mutation positive NSCLC. The AE profile was consistent with previously reported AEs in the literature. Accrual of patients continues and updated data will be presented Figure 1
