A Study of LY3405105 in Participants With Advanced Cancer | NCT03770494

NCT03770494

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
J1F-MC-JZFA	Other Identifier	Eli Lilly and Company
2018-002668-23	EudraCT Number

Status Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
LY3405105	Experimental	This study was designed to be conducted in two phases: Phase 1a: This is a dose-escalation phase with a starting dose of LY3405105 1 milligram (mg) once daily (Part A1) or 2 mg three times per week (Part A2) on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason. Each dose-level will be determined and will have participants enrolled to it based on dose-limiting toxicity rate observed at previous dose-level. Intermediate, alternate, or higher dose levels will be explored if deemed necessary. Phase 1b: This is a dose-expansion phase designed to explore the anti-tumor activity of recommended LY3405105 dose and dosing schedule determined in phase 1a, in participants with multiple tumor types. [Phase 1b was planned but not initiated based on the sponsor's decision and limited efficacy observed in phase 1a]	Drug: LY3405105

Name	Type	Description	Arm Group Labels	Other Names
LY3405105	Drug	Administered orally.	LY3405105

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs)	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.	Cycle 1 (Up To 28 Days)
Phase 1b: Objective Response Rate (ORR): Percentage of Participants With a Confirmed Complete Response (CR) or Partial Response (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.	Baseline through Measured Progressive Disease (Estimated up to 6 Months)

Secondary Outcomes

Measure	Description	Time Frame
Phase 1a (Part A1): Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY3405105	AUC(0-24) of LY3405105	Cycle 1 Day 1 (Predose, 1, 2, 4, 6, 8, 24 hours post-dose)
Phase 1a (Part A1): PK: Area Under the Concentration Versus Time Curve During One Dosing Interval [AUC(Tau)] of LY3405105

Eligibility Module

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Highlands Oncology Group		Fayetteville	Arkansas	72703	United States
Smilow Cancer Hospital at Yale-New Haven

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37531083	Derived	Garralda E, Schram AM, Bedard PL, Schwartz GK, Yuen E, McNeely SC, Ribeiro S, Cunningham J, Wang Y, Urunuela A, Xu X, LoRusso P. A Phase I Dose-Escalation Study of LY3405105, a Covalent Inhibitor of Cyclin-Dependent Kinase 7, Administered to Patients With Advanced Solid Tumors. Oncologist. 2024 Jan 5;29(1):e131-e140. doi: 10.1093/oncolo/oyad215.
32385714

Label	URL
A Study of LY3405105 in Participants With Advanced Cancer	View source

Arm/Group Information

ID	Title	Description
FG000	Part A1 Cohort 1 (1 mg, QD)	Participants received 1 mg LY3405105 once daily (QD) orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG001	Part A1 Cohort 2 (2 mg, QD)	Participants received 2 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG002	Part A1 Cohort 3 (4 mg, QD)	Participants received 3 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG003	Part A1 Cohort 4 (8 mg, QD)	Participants received 8 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG004	Part A1 Cohort 5 (15 mg, QD)	Participants received 15 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG005	Part A1 Cohort 6 (30 mg, QD)	Participants received 30 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG006	Part A1 Cohort 7 (45 mg, QD)	Participants received 45 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG007	Part A1 Cohort 8 (35 mg, QD)	Participants received 35 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG008	Part A1 Cohort 9 (25 mg, QD)	Participants received 25 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG009	Part A1 Cohort 10 (20 mg, QD)	Participants received 20 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG010	Part A2 Cohort 1 (2 mg, TIW)	Participants received 2 mg LY3405105 three times per week (TIW) orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG011	Part A2 Cohort 2 (4 mg, TIW)	Participants received 4 mg LY3405105 TIW orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG012	Part A2 Cohort 3 (8 mg, TIW)	Participants received 8 mg LY3405105 TIW orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
FG013	Phase 1b	This is a dose-expansion phase designed to explore the anti-tumor activity of recommended LY3405105 dose and dosing schedule determined in phase 1a, in participants with multiple tumor types.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0004 subjects FG0014 subjects FG0024 subjects FG0034 subjects FG0045 subjects FG0055 subjects FG0065 subjects FG0073 subjects FG0083 subjects FG0096 subjects FG0104 subjects FG0114 subjects FG0123 subjects FG0130 subjects
Received At Least 1 Dose of Study Drug		FG0004 subjects FG0014 subjects FG0024 subjects FG0034 subjects
COMPLETED		FG0002 subjects FG0011 subjects FG0022 subjects FG0032 subjects FG004
NOT COMPLETED		FG0002 subjects FG0013 subjects FG0022 subjects FG0032 subjects FG004

Type	Comment	Reasons
Lost to Follow-up		FG0000 subjects FG0010 subjects FG0021 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Part A1 Cohort 1 (1 mg, QD)	Participants received 1 mg LY3405105 once daily (QD) orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
BG001	Part A1 Cohort 2 (2 mg, QD)

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase 1a: Number of Participants With Dose Limiting Toxicities (DLTs)

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.

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

Posted

Count of Participants

Participants

Cycle 1 (Up To 28 Days)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part A1 Cohort 1 (1 mg, QD)	Participants received 1 mg LY3405105 once daily (QD) orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 13, 2020	Nov 11, 2021	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jul 20, 2020	Nov 11, 2021	SAP_001.pdf

OG000	Part A1 Cohort 1 (1 mg, QD)	Participants received 1 mg LY3405105 once daily (QD) orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG001	Part A1 Cohort 2 (2 mg, QD)	Participants received 2 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG002	Part A1 Cohort 3 (4 mg, QD)	Participants received 3 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG003	Part A1 Cohort 4 (8 mg, QD)	Participants received 8 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG004	Part A1 Cohort 5 (15 mg, QD)	Participants received 15 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG005	Part A1 Cohort 6 (30 mg, QD)	Participants received 30 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG006	Part A1 Cohort 7 (45 mg, QD)	Participants received 45 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG007	Part A1 Cohort 8 (35 mg, QD)	Participants received 35 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG008	Part A1 Cohort 9 (25 mg, QD)	Participants received 25 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG009	Part A1 Cohort 10 (20 mg, QD)	Participants received 20 mg LY3405105 QD orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG010	Part A2 Cohort 1 (2 mg, TIW)	Participants received 2 mg LY3405105 TIW orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG011	Part A2 Cohort 2 (4 mg, TIW)	Participants received 4 mg LY3405105 TIW orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.
OG012	Part A2 Cohort 3 (8 mg, TIW)	Participants received 8 mg LY3405105 TIW orally on a 28-day cycle until confirmed progressive disease, unacceptable toxicity, or discontinuation for any other reason.