A Study of LY3405105 in Participants With Advanced Cancer

A DLT is a clinically significant adverse event that is possibly related to the study drug and fulfils any one of the following criteria using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v4.0: 1\) Nonhematologic Grade ≥3 toxicity, except nausea, constipation, diarrhoea, vomiting or electrolyte disturbance lasting for \<72 hours and can be controlled with treatment, fatigue/anorexia lasting for \<5 days, transient grade 3 elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST), without evidence of other hepatic injury; 2) Total bilirubin \>2×upper limit of normal (ULN) with ALT/AST \>3×ULN in the absence of cholestasis (alkaline phosphatase \<2×ULN); 3) Grade 4 neutropenia \>5 days duration, Any febrile neutropenia, Grade 4 thrombocytopenia of any duration, Grade 3 thrombocytopenia with clinically significant bleeding, Grade 3/4 anemia or any other significant toxicity deemed to be dose limiting by investigators.

Time frame: Cycle 1 (Up To 28 Days)

Population: All phase 1a participants who received at least one dose of LY3405105 in Cycle 1.

ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.

Time frame: Baseline through Measured Progressive Disease (Estimated up to 6 Months)

Population: ORR is phase 1b primary outcome measure. Phase 1b of the study is not conducted and no participant enrolled, thus no data collected.

DCR is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Time frame: Baseline through Measured Progressive Disease (Up To 349 Days)

Population: All phase 1a participants who received at least one dose of LY3405105.

DoR will be calculated only for responders. It is measured from the date of first evidence of a confirmed CR or PR response to the date of first progression of disease or the date of death due to any cause, whichever is earlier.

Time frame: Date of Confirmed CR or PR to Date of Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)

Population: Zero participants analysed. DoR was not evaluable as there were no participants with CR or PR.

ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.

Time frame: Baseline through Measured Progressive Disease (Up To 349 Days)

Population: All phase 1a participants who received at least one dose of LY3405105.

AUC(0-24) of LY3405105

Time frame: Cycle 1 Day 1 (Predose, 1, 2, 4, 6, 8, 24 hours post-dose)

Population: All part A1 participants of phase 1a who received at least one dose of LY3405105 and had evaluable PK data.

AUC of LY3405105 during one dosing interval of 24 hours \[tau = 24 hours\].

Time frame: Cycle 1 Day 15 (Predose, 1, 2, 4, 6, 8, 24 hours post-dose)

Population: All part A1 participants of phase 1a who received at least one dose of LY3405105 and had evaluable PK data. For Part A1 Cohort 7 (45 mg, QD) and Cohort 9 (25 mg, QD), day 15 PK data was not collected for any participants as study was terminated prior to data collection; thus, zero participants were analysed.

AUC of LY3405105 during one dosing interval of 48 hours \[tau = 48 hours\].

Time frame: Cycle 1 Day 15 (Predose, 1, 2, 4, 6, 8, 24, 48 hours post-dose)

Population: All part A2 participants of phase 1a who received at least one dose of LY3405105 and had evaluable PK data.

AUC(0-∞) of LY3405105.

Time frame: Cycle 1 Day 1 (Predose, 1, 2, 4, 6, 8, 24, 48 hours post-dose)

Population: All part A2 participants of phase 1a who received at least one dose of LY3405105 and had evaluable PK data.

TTR is defined as the time from the date of start of treatment to the date measurement criteria for confirmed CR or PR (whichever is first recorded) are first met.

Time frame: Baseline to Date of Confirmed CR or PR (Estimated up to 6 Months)

Population: Zero participants analysed. TTR was not evaluable as there were no participants with CR or PR.

OS is defined as the time from the date of start of treatment to the date of death due to any cause.

Time frame: Baseline to Date of Death from Any Cause (Estimated up to 12 Months)

Population: OS is a phase 1b outcome measure. Phase 1b of the study is not conducted and no participant enrolled, thus no data collected.

PFS is defined as the time from the date of start of treatment to the first date of radiologically documented progressive disease or the date of death due to any cause, whichever occurs first.

Time frame: Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)

Population: PFS is a phase 1b outcome measure. Phase 1b of the study is not conducted and no participant enrolled, thus no data collected.