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C. Tibor
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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 - 14:30 | Author(s): C. Tibor
- 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
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P3.02c - Poster Session with Presenters Present (ID 472)
- 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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P3.02c-030 - Use of a 200-Mg Fixed Dose of Pembrolizumab for the Treatment of Advanced Non–Small Cell Lung Cancer (NSCLC) (ID 6129)
14:30 - 14:30 | Author(s): C. Tibor
- Abstract
Background:
Previous analyses showed no clinically significant exposure-efficacy relationship for pembrolizumab doses of 2-10 mg/kg. Population pharmacokinetics (popPK) modeling suggested weight-based or fixed pembrolizumab doses could maintain exposures within the established safety/efficacy bounds. Fixed dose advantages include increased convenience, reduced dosing error risk, and less discarded product. Pembrolizumab 200 mg Q3W was evaluated in the KEYNOTE-024 study of pembrolizumab versus platinum-doublet chemotherapy for treatment-naive advanced NSCLC with PD-L1 TPS ≥50% (NCT02142738).
Methods:
Pembrolizumab serum concentration was quantified with an electrochemiluminescence-based immunoassay (lower limit of quantitation, 10 ng/mL). The existing 2-compartment popPK model derived from studies of weight-based pembrolizumab dosing was extended with KEYNOTE-024 concentration-time data. Correlation between pembrolizumab exposure (ie, area under the serum-concentration curve over 6 weeks [AUC~ss-6weeks~]) and efficacy was assessed.
Results:
Median (range) weight was 69.7 kg (38-110) in KEYNOTE-024 and 75 kg (35.7-210) in the existing popPK model studies. In treatment-naive advanced NSCLC, there was a flat relationship between pembrolizumab exposure and efficacy for the 200-mg fixed dose and weight-based doses (linear regression P>0.05). Observed pembrolizumab concentrations for 200 mg (median 1976 μg·d/mL, 90% CI 1124-3322) were consistent with predictions (median 1751 μg·d/mL, 90% prediction interval 955-3136) and fell within the previously observed therapeutic window for 2 and 10 mg/kg (Figure). There was considerable overlap in exposures for 2 mg/kg and 200 mg, regardless of whether weight was >90 or <90 kg for 200 mg (Figure). Figure 1
Conclusion:
Pembrolizumab exposure at 200 mg Q3W is similar to that of 2 mg/kg Q3W. Including data from patients with advanced NSCLC treated with 200 mg did not change the flat exposure-efficacy relationship. Along with the superior PFS and OS provided by pembrolizumab over platinum-doublet chemotherapy as first-line therapy for advanced NSCLC with TPS ≥50%, these data support 200 mg Q3W as an alternative to the approved 2-mg/kg Q3W dose.
