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C. Lin
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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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P2.06-012 - Phase 2 Study of Abemaciclib + Pembrolizumab in KRAS Mutation, PD-L1+, Stage IV Non-Small Cell or Squamous Cell Lung Cancer (ID 3762)
14:30 - 14:30 | Author(s): C. Lin
- Abstract
Background:
Stage IV non-small cell lung cancer (NSCLC) harboring KRAS mutations remains a treatment challenge. Abemaciclib, a small molecular inhibitor of both cyclin-dependent kinase (CDK) 4 and CDK6, demonstrated acceptable safety, tolerability, and single-agent activity for patients with different tumors, including NSCLC. Preclinical evidence suggests a lethal interaction between CDK4 inhibition in lung cells and KRAS oncogenes. Pembrolizumab, a humanized monoclonal antibody against PD-1 protein, is approved in the US for patients with metastatic PD-L1+ NSCLC. Both compounds demonstrated manageable toxicities. We thus aim to study the combination of abemaciclib and pembrolizumab in pretreated patients with NSCLC.
Methods:
This open-label phase 2 study will evaluate safety and preliminary efficacy of abemaciclib 150 mg given orally every 12 hours on a continuous schedule on days 1-21 in combination with intravenous pembrolizumab 200 mg on day 1 of a 21-day cycle to patients in 1 of 3 disease cohorts: KRAS mutation, PD-L1+, stage IV NSCLC (Part A); stage IV NSCLC with squamous histology (Part B); or hormone receptor+, HER2- metastatic breast cancer (Part C). Total target accrual is approximately 75 patients (25 per cohort). Only the 2 NSCLC cohorts will be presented here. Patients eligible for Part A have a confirmed KRAS mutation, PD-L1+ expression score of ≥1%, and are chemotherapy-naïve for metastatic NSCLC. Part B includes patients with predominately squamous NSCLC who have received 1 prior platinum-based chemotherapy for advanced NSCLC. Patients must provide tumor tissue before and after treatment (cycle 3, day 1); have measurable disease, adequate organ function, an ECOG PS ≤1, and a life expectancy ≥12 weeks; and be ≥18 years of age and able to swallow oral medications. The primary objective is to characterize the safety profile of abemaciclib plus pembrolizumab. Secondary objectives include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), characterization of pharmacokinetics, and health outcomes. Patients who receive any study drug will be included in the analyses. Analyses of ORR, DCR, DoR, and PFS will be evaluated according to RECIST v.1.1 and irRECIST. Time-to-event variables will be estimated by Kaplan-Meier methodology. An interim analysis of safety and preliminary efficacy may occur after all patients have completed (or discontinued from) approximately 24 weeks of treatment. The final OS analysis will occur based on data collected for approximately 12 months after the last patient receives treatment.
Results:
Section not applicable
Conclusion:
Section not applicable
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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): C. Lin
- 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.
