The primary purpose of this study is to assess the safety and tolerability of LY2940680 up to the global recommended dose in Japanese participants with advanced solid cancers.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Administered orally
For additional information regarding investigative sites for this trial, contact 1-858-255-5959 Mon - Fri from 9 AM to 5 PM Pacific Time (PST), or speak with your personal physician.
Shizuoka, Japan
For additional information regarding investigative sites for this trial, contact 1-858-255-5959 Mon - Fri from 9 AM to 5 PM Pacific Time (PST), or speak with your personal physician.
Tokyo, Japan
Number of Participants With LY2940680 Dose-Limiting Toxicities (DLT)
DLT was defined as an AE during Cycle 1 that is possibly related to the study drug and meets any one of the following criteria based on NCI CTCAE,version 4.0): Grade(Gr) 3 nonhematological toxicity(tox) with exceptions for made for nausea(ns),vomiting(vm),constipation(cp),diarrhea(dr),fatigue(ft),anorexia(an),alopecia or electrolyte-abnormality(eab) that is manageable with appropriate care.If \>Gr 3 ns,vm,cp,dr,ft,an,or eab persists for\>2 days with maximal supportive intervention,the event was declared a DLT.Transient(≤5 days) Gr 3 liver enzyme elevations,without evidence of other hepatic injury.Gr 3 thrombocytopenia(throm) requiring platelet transfusion or Gr 4 throm.Gr 4 neutropenia of \>5 days duration.Febrile neutropenia(ANC\<1,000/mm3 with a single temperature(temp) of \>38.3 degrees C or a sustained temp of ≥38 degrees C for more than one hour).Tox requiring dose omissions of \>5 days or significant \& deemed by the primary investigator(PI) \& sponsor(sp) to be dose limiting .
Time frame: Cycle 1 (28 Days)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680 and a Major Metabolite of LY2940680 (LSN3185556)
Maximum Concentration (Cmax) of LY2940680 and a Major Metabolite of LY2940680 (LSN3185556).
Time frame: Cycle1 Day1: Predose, 0.5,1,2,4, 6, 8, 10-12 hours; Cycle 1 Day15: Predose, 0.5,1,2,4, 6, 8, 10-12 hours
Pharmacokinetics (PK): Area Under the Concentration Time Curve From 0 to 24 Hours (AUC[0-24]) of LY2940680 and a Major Metabolite of LSN3185556
Pharmacokinetics (PK): Area Under the Concentration time Curve From 0 to 24 Hours (AUC\[0-24\]) of LY2940680 and a Major Metabolite of LSN3185556.
Time frame: Cycle1 Day1: Predose, 0.5,1,2,4, 6, 8, 10-12 hours; Cycle 1 Day15: Predose, 0.5,1,2,4, 6, 8, 10-12 hours
Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR])
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size (\<10 millimeter \[mm\] short axis). PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameters. ORR calculated as: (sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100.
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Time frame: Baseline Until Disease Progression or Death Due to Any Cause (Up to 29 Months)
Pharmacodynamic (PD): Percentage Change From Baseline in Gene Expression Level of Hedgehog (Hh) Regulated Genes (Gli1) in Skin
Percentage Change From Baseline in Gene Expression Level of Hedgehog (Hh) Regulated Genes (Gli1) in Skin.
Time frame: Baseline, Cycle 1 Day15