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S. Kim
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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-005 - Phase Ib Trial of Afatinib and BI 836845 in Advanced NSCLC: Dose Escalation and Safety Results (ID 4719)
14:30 - 14:30 | Author(s): S. Kim
- Abstract
Background:
Insulin-like growth factor (IGF) signaling is implicated in acquired resistance to EGFR TKIs in NSCLC. BI 836845 is an IGF ligand-neutralizing antibody that binds to IGF-1 and IGF-2, and inhibits their growth-promoting activities. This Phase Ib trial evaluates BI 836845 in combination with afatinib in patients with NSCLC progressing following prior treatment with EGFR TKIs or platinum-based chemotherapy (NCT02191891).
Methods:
The trial consists of two sequential parts: a dose confirmation part (Part A, reported here) and an expansion part (Part B). In Part A, eligible patients were aged ≥18 years with advanced and/or metastatic NSCLC progressing on EGFR TKIs (patients with EGFR mutations) or platinum-based chemotherapy. Patients receiving prior afatinib therapy below the assigned dose level or <30mg/day, or with progression on an insufficient dose of EGFR TKI prior to the study, were excluded. Part A used a 3+3 dose-escalation design with a starting dose of BI 836845 1,000mg/week (1-hour intravenous infusion) plus oral afatinib 30mg/day, in 4-week cycles. Primary endpoints were the maximum tolerated dose (MTD) of BI 836845 in combination with afatinib, and the occurrence of dose-limiting toxicities (DLTs) during Cycle 1.
Results:
At data cut-off (18 April 2016), 16 patients were treated (BI 836845 1,000mg/afatinib 30mg [n=4]; BI 836845 1,000mg/afatinib 40mg [n=12]). Median age (range) was 60 (48–77) years. Fourteen (88%) patients had activating EGFR mutations. Nine (56%) patients discontinued treatment, mostly due to progressive disease (one patient discontinued BI 836845 for other reasons); seven patients remain on treatment. During Cycle 1, 0/3 patients (afatinib 30mg) and 0/12 patients (afatinib 40mg) had a DLT (one patient [afatinib 30mg] was replaced during Cycle 1 due to a non-DLT adverse event [AE]). Therefore, the MTD and recommended Phase II dose (RP2D) was determined to be BI 836845 1,000mg/week in combination with afatinib 40mg/day. All patients experienced at least one drug-related AE; the most common were diarrhea (n=12; 75%), paronychia (n=11; 69%) and rash (n=10; 63%). Drug-related AEs were mostly grade 1/2 (one patient [afatinib 30mg] had grade 3 stomatitis). No drug-related AEs led to discontinuation and no dose reductions were required for BI 836845 or afatinib.
Conclusion:
The MTD and RP2D of BI 836845 was determined as 1000mg/week in combination with afatinib 40mg/day in patients who have failed prior EGFR TKIs or chemotherapy. This combination demonstrated a clinically manageable safety profile, consisting of AEs commonly associated with afatinib. The expansion part (Part B) is ongoing.
