Virtual Library
Start Your Search
A. Szczęsna
Author of
-
+
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
-
+
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): 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.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
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)
-
+
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 - 14:30 | 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.
-
+
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)
-
+
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 - 14:30 | 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
