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T. Bogenrieder
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-100 - Phase Ib Trial of Afatinib and BI 836845 in Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 1767)
09:30 - 09:30 | Author(s): T. Bogenrieder
- Abstract
Background:
Patients harboring epidermal growth factor receptor (EGFR)-mutated NSCLC treated with EGFR tyrosine kinase inhibitors (TKIs) invariably develop acquired resistance (AR). The mechanisms of AR are unknown in 30–40% of patients. In pre-clinical studies, insulin-like growth factor (IGF) signaling has been implicated in AR to EGFR TKIs in the absence of other known mechanisms including T790M mutation. It is hypothesized that an EGFR TKI combined with an IGF inhibitor can overcome this resistance. BI 836845 is a fully human, affinity-optimized, IGF ligand-neutralizing antibody. BI 836845 binds to IGF-1 and IGF-2 and neutralizes growth-promoting signaling. Preliminary results from two Phase I studies have shown a tolerable safety profile. This trial was designed to evaluate the safety and anti-tumor activity of BI 836845 combined with afatinib in patients with EGFR-mutated NSCLC progressing following prior treatment with reversible or irreversible EGFR TKIs.
Methods:
This is an open-label, dose-escalation trial in Korea, Taiwan and Singapore (NCT02191891; Study 1280.16) consisting of a dose confirmation part (Part A) followed by an expansion part (Part B). Eligible patients are aged ≥18 years with advanced and/or metastatic NSCLC progressing during continuous treatment with single-agent EGFR TKI ≤30 days immediately prior to study treatment, with documented presence of an activating EGFR mutation and lacking an EGFR T790M mutation (confirmed by central testing in Part B). Patients with prior afatinib treatment at a dose below the assigned dose level (Part A only) or <30 mg/day (Parts A and B), or disease progression on an insufficient dose of EGFR TKI immediately prior to study in the investigator’s opinion, or >2 (Part A) or >1 (Part B) prior EGFR TKI treatment regimens for relapsed or metastatic NSCLC are excluded. Part A follows a 3+3 design to determine the MTD and/or recommended Phase 2 dose (RP2D) of BI 836845 combined with afatinib (starting dose: BI 836845 1000 mg/week intravenous infusion over 60 minutes plus oral afatinib 30 mg/day administered in 4-week courses). Patients receive continuous treatment until disease progression, intolerable adverse events (AEs), consent withdrawal or non-compliance with the study protocol. Patients are entered sequentially into escalating/de-escalating dose tiers to determine the MTD based on the occurrence of dose-limiting toxicities (DLTs) during Course 1 (3–6 patients per cohort); 6 additional patients will be enrolled in an extension cohort at the R2PD. Part B consists of two separate expansion cohorts of patients previously treated with irreversible EGFR TKIs (e.g. afatinib, dacomitinib; Cohort 1) and those previously treated with reversible EGFR TKIs (gefitinib or erlotinib; Cohort 2). In each cohort, 18 patients will be treated with the RP2D determined in Part A. Primary endpoints are the MTD and DLTs during Course 1 (Part A) and the objective response assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Part B). Secondary endpoints include disease control, time to objective response, duration of objective response, and pharmacokinetic parameters. AEs are evaluated according to Common Terminology Criteria for AEs (CTCAE) v4.03. All analyses will be descriptive and exploratory.
Results:
Not applicable.
Conclusion:
Not applicable.
