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A. Szczęsna
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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)
14:20 - 15:50 | Author(s): A. Szczęsna
- 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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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-006 - Phase I/II Dose Escalation Study of L-DOS47 as a Monotherapy in Non-Squamous Non-Small Cell Lung Cancer Patients (ID 4455)
14:30 - 15:45 | Author(s): A. Szczęsna
- Abstract
Background:
L DOS47, a cancer therapeutic designed to exploit the acidic tumour extracellular environment, is a protein conjugate consisting of a urease conjugated to a camelid monoclonal antibody (AFAIKL2) that is targeted to the CEACAM6 antigenic tumour marker. The AFAIKL2 antibody serves as a targeting agent to deliver the enzyme to the tumor sites while the urease enzyme converts urea, an abundant natural metabolite, into ammonia and generates a local pH increase. The combined effect of ammonia toxicity and pH increase is cytotoxic to cancer cells in culture and in xenograft models. This first in human study of L DOS47 was designed to define the maximum tolerated dose of multiple doses of L-DOS47 administered intravenously to patients with non-squamous NSCLC when given as a monotherapy.
Methods:
Stage IIIb or IV histologically confirmed non-squamous NSCLC patients (aged ≥18 yrs, ECOG PS ≤2) receive multiple cycles of L-DOS47 during the study treatment period. L-DOS47 is administered once weekly over 14 days followed by 7 days rest in each treatment cycle. Patients are recruited into cohorts and received the same dose of L-DOS47 on Days 1 and 8 of each treatment cycle. Dose levels of L-DOS47 are escalated in further cohorts following a review of safety data by the Trial Steering Committee.
Results:
Fifty-five (55) pts (median age 61, 53% male) were enrolled in sixteen cohorts (dose levels: 0.12 to 13.55 µg/kg) in four Polish centers. L-DOS47 was well tolerated at the dose levels reviewed. One (1) DLT was reported in a cohort 13 patient (spinal pain). None of the patients treated to date have had a partial or complete response as defined by RECIST v1.1. Thirty-two (32) patients had an overall response of stable disease after completing two cycles of L-DOS47. Thirteen (13) of the 32 patients had a decrease in the sum of diameters of target lesions. One (1) patient in cohort 9 was dosed for 10 cycles without disease progression.
Conclusion:
L-DOS47 monotherapy is well tolerated at dose levels up to 13.55µg/kg.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-045 - Patritumab plus Erlotinib in EGFR Wild-Type Advanced Non–Small Cell Lung Cancer (NSCLC): Part a Results of HER3-Lung Study (ID 5473)
14:30 - 15:45 | Author(s): A. Szczęsna
- Abstract
Background:
Patritumab is a fully human monoclonal antibody that inhibits human epidermal growth factor receptor 3. In a subgroup analysis of the phase 2 HERALD study, addition of patritumab to erlotinib increased progression-free survival (PFS) in advanced NSCLC patients with high tumor expression of heregulin mRNA (HRG-High); a similar safety profile was seen with patritumab+erlotinib versus erlotinib. This 2-part, phase 3 study (HER3-Lung) investigated erlotinib±patritumab in advanced, EGFR wild-type NSCLC patients previously treated with a platinum doublet. The primary objective of Part A was to confirm PFS improvement in HRG-High subjects.
Methods:
HER3-Lung was a 2-part, randomized, placebo-controlled, double-blind study. Subjects aged ≥20 years with known HRG expression, advanced NSCLC previously treated with 1–2 systemic therapies including a platinum doublet, and EGFR wild-type (if adenocarcinoma histology) were eligible. Subjects were stratified by HRG expression, histology subtype (adenocarcinoma, squamous-cell carcinoma/NOS), ECOG performance status (0–1), and best response to most recent therapy (CR/PR/SD, PD). Within each stratum, subjects were randomized 1:1 to erlotinib+patritumab or erlotinib+placebo.
Results:
One-hundred forty-five subjects were randomized, and 125 had discontinued study treatment prior to the data cutoff date. Most common reason for discontinuation was progressive disease (n=70). In the erlotinib+patritumab and erlotinib+placebo arms, respectively, treatment-emergent adverse events (TEAEs) grade ≥3 were reported in 40.5% and 46.5% and any grade serious TEAEs in 35.1% and 36.6% of subjects. Most common TEAEs (by subject) in the erlotinib+patritumab and erlotinib+placebo arms, respectively, were diarrhea (51.4%, 31%) and rash (37.8%, 36.6%). Patritumab did not increase erlotinib efficacy in the intent-to-treat group or HRG subgroups (Table). The study was stopped at the end of Part A because efficacy criteria to proceed into Part B were not reached.
Conclusion:
HER-3Lung did not confirm patritumab efficacy in the HRG-High subgroup. Safety of patritumab in combination with erlotinib was acceptable.Figure 1
