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C.K. Obasaju
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OA23 - EGFR Targeted Therapies in Advanced NSCLC (ID 410)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:O.T. Brustugun, S. Lu
- Coordinates: 12/07/2016, 14:20 - 15:50, Stolz 2
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OA23.02 - Efficacy and Safety of Necitumumab Continuation Monotherapy in Patients with EGFR-Expressing Tumors in SQUIRE, a Phase 3 Study (ID 4283)
14:30 - 14:40 | Author(s): C.K. Obasaju
- Abstract
- Presentation
Background:
SQUIRE (NCT00981058) demonstrated adding necitumumab (N) to gemcitabine/cisplatin (GC) improved survival in patients with Stage IV squamous NSCLC (SQ-NSCLC). Retrospective analysis revealed consistent treatment effect in favor of patients receiving N monotherapy as continuation after chemotherapy (CT) (GC+N continuation patients) versus continuation therapy-eligible GC arm patients (GC non-progressors). In the EU, N is approved for patients with EGFR-expressing tumors. We repeated the analysis in this patient population.
Methods:
Patients with Stage IV SQ-NSCLC were randomized 1:1 for ≤6 cycles of G (1250 mg/m[2] iv, Days [d] 1,8) and C (75 mg/m[2] iv, d1) either with or without N (800 mg iv, d1,8). Patients in GC+N without progression continued N until progressive disease (PD). SQUIRE included mandatory tissue collection. EGFR protein expression was assessed by IHC in a central lab (Dako EGFR PharmDx kit). Analyses were done in EGFR-expressing patients (EGFR >0). Patients who received ≥4 cycles of CT without PD were included. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. 95% CIs and hazard ratios estimated using stratified Cox proportional hazards model.
Results:
Of 1093 patients (ITT population), 982 patients (89.8%) had evaluable IHC assay results; 935/982 (95.2%) had EGFR>0. GC+N arm continuation therapy patients included 228 patients with EGFR>0 and 194 patients (EGFR>0) were GC arm non-progressors. Baseline characteristics were similar except gender (Males: 81% in GC+N vs 91% in GC arm). CT exposure was balanced. Median OS from randomization in GC+N vs GC was 16.1 vs 14.9 months; HR 0.76 (95% CI, 0.61, 0.95). Median PFS in GC+N vs GC was 7.4 vs 6.9 months; HR 0.81 (95% CI, 0.66, 1.00). Figure 1
Conclusion:
In patients with EGFR-expressing tumors, a consistent treatment effect in favor of GC+N continuation maintenance compared to GC non-progressors was observed, similar to ITT population with no unexpected increases in AEs.
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-065 - Lack of Drug-Drug Interaction (DDI) between Necitumumab and Gemcitabine or Cisplatin: A Phase 2, Open-Label, Nonrandomized Study (ID 6195)
14:30 - 14:30 | Author(s): C.K. Obasaju
- Abstract
Background:
Necitumumab is a recombinant human immunoglobulin G1 monoclonal antibody that blocks the ligand-binding site of EGFR. This study evaluated the effects of necitumumab on the pharmacokinetics (PK) of gemcitabine and cisplatin, and compared the PK of 2 necitumumab drug products manufactured by 2 different processes: Process C and Process D.
Methods:
Study participants included adult patients with advanced or metastatic malignant solid tumors (except colorectal tumors with KRAS mutation) that were resistant to standard therapy or for which no standard therapy was available. Patients enrolled in 2 cohorts received intravenous (IV) infusions of necitumumab 800 mg (cohort 1: Process C drug product; cohort 2: Process D drug product) on Day 3 of the PK run-in period following IV infusions of gemcitabine 1250 mg/m[2] and cisplatin 75 mg/m[2] on Day 1 of the PK run-in period, and subsequent infusions (same doses) of gemcitabine on Days 1 and 8, cisplatin on Day 1, and necitumumab on Days 1 and 8 of each 3‑week cycle. The effect of necitumumab on the PK of gemcitabine and cisplatin was evaluated in the PK run-in period and cycle 1 of cohort 1, and the PK of Process C and D necitumumab drug products were compared in PK run-in periods of cohorts 1 and 2. Blood was drawn immediately before and at regular intervals after each infusion in the PK run-in period to determine concentrations of necitumumab, gemcitabine, and cisplatin for PK parameter computation. Study treatment could continue up to 6 cycles and was discontinued for disease progression, unacceptable toxicity, or other withdrawal criteria. Patients who had not progressed had an option to continue necitumumab monotherapy until withdrawal criteria were met.
Results:
Eighteen and 20 patients were enrolled in cohort 1 and cohort 2, respectively. Coadministration of necitumumab did not alter dose-normalized area under the plasma concentration curves (AUCs) of gemcitabine and cisplatin (geometric least squares mean [GLSM] ratios: 90% CI;1.184: 0.960‑1.459 and 1.105: 1.063-1.148, respectively). Similarly, coadministration of gemcitabine and cisplatin with necitumumab did not alter AUC of necitumumab (GLSM ratio:90% CI; 1.077: 0.988-1.174). PK exposure parameters for both Process C and Process D drug products were similar, with GLSM ratios for AUC close to 1 and 90% CIs within the range of 80‑125%. No new safety signals were reported.
Conclusion:
No clinically relevant DDIs between necitumumab and gemcitabine or cisplatin were observed. Process C and Process D drug products had similar PK profiles. ClinicalTrials.gov Identifier:NCT01606748; Funding: Eli Lilly.
