Abstract 2777
Background
Abemaciclib, a selective CDK4 & 6 inhibitor, demonstrated single-agent activity in NSCLC and melanoma (Patnaik et al., 2016). Clinical data demonstrate abemaciclib penetrates the blood brain barrier resulting in comparable concentrations in tissues and plasma (Sahebjam et al., 2016).
Methods
Study JPBO is a Simon 2-stage trial evaluating abemaciclib in 6 pt cohorts with BM secondary to HR+ breast cancer, NSCLC, or melanoma. Here, we report NSCLC and melanoma cohorts. Pts with ≥1 new or not previously irradiated BM ≥ 10mm or a progressive BM previously irradiated were eligible. Abemaciclib was orally administered BID on a continuous dosing schedule. Primary endpoint was objective intracranial response rate (OIRR; [confirmed CR+PR]) based on Response Assessment in Neuro-Oncology BM response assessment criteria (RANO-BM). Secondary endpoints included intracranial clinical benefit rate, PFS, OS, and safety.
Results
28 (NSCLC) and 23 (MEL) pts were enrolled and 23 (NSCLC) and 22 (MEL) were evaluable. Pts had a median of 2 prior systemic therapies in the metastatic setting. 35% (NSCLC) and 46% (MEL) of pts had prior whole brain radiotherapy. 35% (NSCLC) and 27% (MEL) pts had stereotactic radiotherapy. Median time from radiation to study enrollment was 4.8 (NSCLC) to 5.6 (MEL) months. No confirmed intracranial response was observed (OIRR 0% for both cohorts). 21.7% (NSCLC) and 13.6% (MEL) of pts showed a decrease in the sum of their intracranial target lesions. ICBR (CR+PR+SD persisting for > 6 months) was 26.1% (NSCLC) and 9.1% (MEL). Median PFS was 1.5 months (95% CI, 1.4-2.8) for NSCLC and 1.2 months (95% CI, 1.0-1.6) for MEL. Median OS was 7.1 months (95% CI, 3.7-9.4) for NSCLC and 2.9 months (95% CI, 1.2-4.3) for MEL. Based on efficacy results, enrollment closed at end of stage 1. Safety and tolerability were similar as previously reported for abemaciclib.
Conclusions
There was limited intracranial clinical activity for abemaciclib monotherapy in NSCLC and MEL pts in this study; OIRR and short median PFS suggest that no further studies for abemaciclib monotherapy are warranted in this pt population.
Clinical trial identification
NCT02308020.
Editorial acknowledgement
Medical writing assistance was provided by Kristi Gruver, employee of Eli Lilly and Company.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
E. Le Rhun: Advisory / Consultancy, Research grant / Funding (institution), Oscar Lambert Center, Lille, FR: Mundipharma; Research grant / Funding (institution), University Hospital, Lille, FR: Amgen; Advisory / Consultancy, personal fees: Novartis; Advisory / Consultancy, personal fees: Daiichi Sankyo; Advisory / Consultancy, personal fees: Abbvie. G. Jerusalem: Advisory / Consultancy, Non-remunerated activity/ies, per patient investigator fee: Eli Lilly and Company; Research grant / Funding (self), Non-remunerated activity/ies, personal fees: Novartis; Research grant / Funding (self), Non-remunerated activity/ies, personal fees: Roche; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: Pfizer; Advisory / Consultancy, personal fees: Celgene; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: Amgen; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: BMS; Advisory / Consultancy, personal fees: Puma Technology; Advisory / Consultancy, Non-remunerated activity/ies, personal fees: AstraZeneca; Advisory / Consultancy, personal fees: Daiichi Sankyo; Advisory / Consultancy, personal fees: Abbvie. D. Subramaniam: Advisory / Consultancy, personal fees: AstraZeneca; Advisory / Consultancy, personal fees: Takeda Oncology; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech. Y. Chen: Shareholder / Stockholder / Stock options, Full / Part-time employment, employee and stock options: Eli Lilly and Company. P.F. Conte: Research grant / Funding (self): Novartis; Travel / Accommodation / Expenses, travel grant: Eli Lilly and Company; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Travel / Accommodation / Expenses, travel grant: Celgene; Travel / Accommodation / Expenses, travel grant: Tesaro. All other authors have declared no conflicts of interest.
Resources from the same session
5658 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Early Diagnosis of Colorectal Cancer
Presenter: Tianyu Liu
Session: Poster Display session 2
Resources:
Abstract
5779 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Prediction of The Efficacy of Conversion Therapy for Colorectal Cancer Liver Metastases
Presenter: Wenju Chang
Session: Poster Display session 2
Resources:
Abstract
4672 - mCRC gene profiling using the Idylla platform
Presenter: Christopher Bricogne
Session: Poster Display session 2
Resources:
Abstract
3393 - PIK3CA mutation in metastatic colorectal cancer (mCRC): association with clinico-pathological features and outcome
Presenter: Valentina Fanotto
Session: Poster Display session 2
Resources:
Abstract
1317 - Patient-Derived Xenografts (PDX) Identifies JMJD6 Inhibitor as an Effective Therapeutic Medicine in Colorectal Cancer.
Presenter: Feng Ye
Session: Poster Display session 2
Resources:
Abstract
1228 - DACH1 induced stemness of intestinal organoids by directly suppressing BMP signaling and contributes to intestinal tumorigenesis
Presenter: Xiang Hu
Session: Poster Display session 2
Resources:
Abstract
1147 - miR-148a inhibits early relapsed colorectal cancers and the secretion of VEGF by indirectly targeting HIF-1α under non-hypoxia/hypoxia conditions
Presenter: Hsiang-lin Tsai
Session: Poster Display session 2
Resources:
Abstract
1158 - Long noncoding RNA CASC21 promotes cell proliferation and metastasis in colon cancer.
Presenter: Qun Zhang
Session: Poster Display session 2
Resources:
Abstract
1259 - Prognostic and Predictive Impact On FMS-like Tyrosine Kinase 3 (FLT3) Amplification In Patients With Metastatic Colorectal Cancer
Presenter: Hiroko Hasegawa
Session: Poster Display session 2
Resources:
Abstract
1452 - RBP-Jκ in colon cancer cells facilitates tumor associated macrophages (TAMs)-induced cell metastasis by secreting CXCL11
Presenter: Meng jie Liu
Session: Poster Display session 2
Resources:
Abstract