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| ID | Type | Description | Link |
|---|---|---|---|
| I6F-JE-JJCC | Other Identifier | Eli Lilly and Company |
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The purpose of this study is to evaluate the tolerability of the study drug LY3039478 in Japanese participants with advanced solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 25 mg LY3039478 | Experimental | Participants received 25 milligrams (mg) of LY3039478, administered orally three times per week (TIW) in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
|
| 50 mg LY3039478 | Experimental | Participants received 50 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY3039478 | Drug | Administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With LY3039478 Dose-Limiting Toxicities (DLTs) | DLT was defined as an adverse event (AE) that occurred during Cycle 1 (first 28 days) related to the study drug and met one of the following criteria per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. These criteria included: CTCAE Grade greater than or equal to (≥) 3 non-hematological toxicity, with exceptions for nausea, vomiting, or constipation, and asymptomatic electrolyte disturbances that can be controlled with standard treatment; Grade 4 hematological toxicity of greater than (>) 5 days duration; Grade ≥ 3 anemia requiring transfusion; any febrile neutropenia; neutropenia needing granulocyte-colony stimulating factors (GCSFs); Grade 3 thrombocytopenia with bleeding or requiring platelet transfusion; Grade 4 thrombocytopenia. | Cycle 1 (Up to 28 Days) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR): Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) |
|
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Inclusion Criteria:
Exclusion Criteria:
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| 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 |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kashiwa | Chiba | 277 8577 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32939607 | Derived | Doi T, Tajimi M, Mori J, Asou H, Inoue K, Benhadji KA, Naito Y. A phase 1 study of crenigacestat (LY3039478), the Notch inhibitor, in Japanese patients with advanced solid tumors. Invest New Drugs. 2021 Apr;39(2):469-476. doi: 10.1007/s10637-020-01001-5. Epub 2020 Sep 16. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 25 mg LY3039478 | Participants received 25 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
| FG001 | 50 mg LY3039478 | Participants received 50 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | 25 mg LY3039478 | Participants received 25 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
| BG001 | 50 mg LY3039478 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Number of Participants With LY3039478 Dose-Limiting Toxicities (DLTs) | DLT was defined as an adverse event (AE) that occurred during Cycle 1 (first 28 days) related to the study drug and met one of the following criteria per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. These criteria included: CTCAE Grade greater than or equal to (≥) 3 non-hematological toxicity, with exceptions for nausea, vomiting, or constipation, and asymptomatic electrolyte disturbances that can be controlled with standard treatment; Grade 4 hematological toxicity of greater than (>) 5 days duration; Grade ≥ 3 anemia requiring transfusion; any febrile neutropenia; neutropenia needing granulocyte-colony stimulating factors (GCSFs); Grade 3 thrombocytopenia with bleeding or requiring platelet transfusion; Grade 4 thrombocytopenia. | All participants with evaluable DLT data in Cycle 1 (the first 28 days) had received greater than or equal to (≥) 75% of the assigned dose during Cycle 1 or had experienced a DLT during Cycle 1. | Posted | Count of Participants | Participants | No | Cycle 1 (Up to 28 Days) |
|
Baseline to end of the follow-up (Up To 100 Weeks)
All enrolled participants who received at least one dose of LY3039478.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 25 mg LY3039478 | Participants received 25 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 | ClinicalTrials.gov@lilly.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 12, 2019 | May 30, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 2, 2019 | May 30, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| C000654634 | crenigacestat |
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| Baseline through Measured Progressive Disease (Up To 100 Weeks) |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3039478 | PK: Cmax of LY3039478 was reported. | Cycle 1, Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose); Cycle 1 Day 22 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose) |
| PK: Area Under the Plasma Concentration-Time Curve (AUC) From 0 to 24 Hours (AUC (0-24)) of LY3039478 | PK: AUC (0-24) of LY3039478 was reported. | Cycle 1, Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose); Cycle 1 Day 22 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose) |
| Japan |
Participants received 50 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Region of Enrollment | Count of Participants | Participants | No |
|
| Description |
|---|
| OG000 | 25 mg LY3039478 | Participants received 25 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
| OG001 | 50 mg LY3039478 | Participants received 50 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
|
|
| Secondary | Overall Response Rate (ORR): Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) |
| All enrolled participants who received at least one dose of LY3039478. | Posted | Number | percentage of participants | Baseline through Measured Progressive Disease (Up To 100 Weeks) |
|
|
|
| Secondary | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3039478 | PK: Cmax of LY3039478 was reported. | All enrolled participants who received at least one dose of LY3039478 and had at least one evaluable PK data. Number analyzed refer to participants evaluable at specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | Cycle 1, Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose); Cycle 1 Day 22 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose) |
|
|
|
| Secondary | PK: Area Under the Plasma Concentration-Time Curve (AUC) From 0 to 24 Hours (AUC (0-24)) of LY3039478 | PK: AUC (0-24) of LY3039478 was reported. | All enrolled participants who received at least one dose of LY3039478 and had at least one evaluable PK data. Number analyzed refer to participants evaluable at specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours per milliliter(ng*h/mL) | Cycle 1, Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose); Cycle 1 Day 22 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose) |
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|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 4 |
| 4 |
| EG001 | 50 mg LY3039478 | Participants received 50 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. | 1 | 7 | 0 | 7 | 6 | 7 |
| Supraventricular tachycardia | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
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| Visual impairment | Eye disorders | MedDRA 22.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Lung infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Tinea pedis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Lipase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
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| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Hemiplegia | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Delirium | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Hair colour changes | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Cycle 1, Day 22 |
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| Cycle 1, Day 22 |
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