Back to resultsA Study of AK-01 (LY3295668) in Solid Tumors
Primary Purpose
Neoplasms, Neoplasm Metastasis, Triple Negative Breast Neoplasms
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
LY3295668
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms
Eligibility Criteria
Inclusion Criteria:
- Have received at least 1 but no more than 4 prior systemic therapies
- Have adequate organ function
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- Have estimated life expectancy greater than or equal to (≥)12 weeks
- Have fully recovered from radiation therapy or surgery, and are recovering from any acute adverse effects of other cancer therapies
- Have discontinued all chemotherapy, investigational therapy, molecularly-targeted therapy, and cancer-related hormonal therapy at least 14 days prior, biologic or immunotherapeutic therapy at least 21 days prior, or mitomycin-C or nitrosoureas at least 6 weeks prior
- Female participants with reproductive potential agree to use 2 forms of highly effective contraception during the study and for the following 3 months
- Male participants must use a barrier method of contraception during the study and for the following 3 months
Phase 1
- Have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor)
Phase 2
- Have disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
Have evidence of a solid tumor that is locally advanced and/or metastatic, and in:
- Small Cell Lung Cancer (SCLC), must have failed platinum-containing therapy
- Breast Cancer, be Estrogen Receptor positive and/or Progesterone Receptor positive, but Human Epidermal Growth Factor Receptor 2 (HER2) negative, and must have failed a hormone therapy and a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor
- Triple negative breast cancer (TNBC) and failed standard therapy
- Squamous cell cancers of the head neck associated with the human papilloma virus (HPV), and have failed standard therapy
- Other solid tumor type that has been approved by the sponsor
Exclusion Criteria:
- Have symptomatic central nervous system (CNS) metastasis (unless asymptomatic and not current receiving corticosteroids) or a primary tumor of the CNS
- Have a medical condition that precludes participation (swallowing disorder, organ transplant, pregnant or nursing, HIV, active Hepatitis B or C, cardiac disease, history of major surgery in upper gastrointestinal (GI) tract or GI disease, hypokalemia, hypomagnesaemia or hypocalcaemia that cannot be controlled)
Sites / Locations
- Cross Cancer Institute
- Jewish General Hospital
- McGill University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
25 milligrams (mg) LY3295668 (Phase 1)
50 mg LY3295668 (Phase 1)
75 mg LY3295668 (Phase 1)
25 mg LY3295668 (Phase 2)
Arm Description
25 milligrams (mg) LY3295668 twice daily (BID) administered orally in 21-day cycles.
50 mg LY3295668 BID administered orally in 21-day cycles.
75 mg LY3295668 BID administered orally in 21-day cycles.
25 mg LY3295668 BID administered orally in 21-day cycles.
Outcomes
Primary Outcome Measures
Phase 1: Maximum Tolerated Dose
Maximum Tolerated Dose (MTD) was defined as the dose immediately below the dose at which ≥2/3, ≥2/6, or ≥3/9 participants in a cohort experienced a dose limiting toxicity (DLT) during the first 21 days of treatment (Cycle 1) in Phase 1.
Phase 2: Percentage of Participants Who Achieved Partial Response (PR) or Complete Response (CR) [Objective Response Rate (ORR)]
Objective response rate (ORR) was defined as a percentage of responders who achieved complete response or partial response (CR+PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Complete response (CR) is defined as disappearance of all target (and non-target) lesions, and no appearance of new lesion. Partial response (PR) was defined as at least a 30% decrease in the sum of longest diameters (LD) of target lesions, taking as reference the baseline sum of LD, no progression of non-target lesions, and no appearance of new lesions.
Secondary Outcome Measures
Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events
A treatment-emergent adverse event (AE) is an AE that started or worsened (increased in severity) from the treatment start date to 30 days after the treatment end date. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events
A treatment-emergent adverse event (AE) is an AE that started or worsened (increased in severity) from the treatment start date to 30 days after the treatment end date. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
Phase 2: Pharmacokinetic (PK): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC[0-12]) (Phase 2)
Area under the plasma concentration-time curve for LY3295668 from time zero to 12 hours.
Phase 2: PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC[0-24])
Area under the plasma concentration-time curve for LY3295668 from time zero to 24 hours.
Phase 2: PK: Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration for LY3295668.
Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax)
Time of maximum observed plasma concentration of LY3295668.
Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2)
Apparent terminal elimination half-life of LY3295668.
Phase 2: PK: Apparent Total Plasma Clearance (CL/F)
Apparent total plasma clearance of LY3295668.
Phase 2: PK: Apparent Volume of Distribution (Vz/F)
Apparent volume of distribution of LY3295668.
Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 White Blood Cell Count (WBC)
Presented are participants with the worst post-baseline WBC Grade >= 3 using the National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events version 4.03 (CTCAE v4.03). where Grade 1: < Lower Limit Normal (LLN) - 3000/mm3; <LLN - 3.0 x10e9/L, Grade 2: <3000 - 2000/mm3; <3.0 - 2.0 x10e9/L, Grade 3: <2000 - 1000/mm3; <2.0 1.0 x10e9/L, Grade 4: <1000/mm3; <1.0 x10e9/L.
Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Neutrophils (Segmented and Blended)
Presented are participants with the worst post-baseline neutrophils Grade >=3 using the NCI-CTCAE v4.03 where Grade 1: < LLN - 1500/mm3; <LLN - 1.5 x10e9/L, Grade 2: <1500 - 1000/mm3; <1.5 - 1.0 x10e9/L, Grade 3: <1000 - 500/mm3; <1.0 - 0.5 x10e9/L, Grade 4: <500/mm3; <0.5 x 10e9/L.
Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Lymphocytes
Presented are participants with the worst post-baseline lymphocytes Grade >=3 using the NCI-CTCAE version 4.03 where Grade 1: <LLN - <800/mm3, <LLN - 0.8 x 10e9/L, Grade 2: <800 - 500/mm3; <0.8 - 0.5 x 10e9/L, Grade 3: <500 - 200/mm3; <0.5 - 0.2 x 10e9/L, <200mm3; <0.2 x 10e9/L.
Full Information
NCT ID
NCT03092934
First Posted
March 22, 2017
Last Updated
June 29, 2021
Sponsor
Eli Lilly and Company
Collaborators
AurKa Pharma Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03092934
Brief Title
A Study of AK-01 (LY3295668) in Solid Tumors
Official Title
A Phase I/II Open-Label Multicenter Study to Evaluate the Safety and Efficacy of AK-01 as Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
May 29, 2017 (Actual)
Primary Completion Date
April 20, 2020 (Actual)
Study Completion Date
April 20, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
Collaborators
AurKa Pharma Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This two-part study consists of a phase 1 dose escalation study in participants with locally advanced or metastatic solid tumors, and a phase 2 portion in up to 3 groups with either small cell lung cancer, breast cancer and/or one other solid tumor type.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Neoplasm Metastasis, Triple Negative Breast Neoplasms, Head and Neck Neoplasms, Breast Neoplasms, Solid Tumor, Adult, Small Cell Lung Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Open-Label
Allocation
Non-Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
25 milligrams (mg) LY3295668 (Phase 1)
Arm Type
Experimental
Arm Description
25 milligrams (mg) LY3295668 twice daily (BID) administered orally in 21-day cycles.
Arm Title
50 mg LY3295668 (Phase 1)
Arm Type
Experimental
Arm Description
50 mg LY3295668 BID administered orally in 21-day cycles.
Arm Title
75 mg LY3295668 (Phase 1)
Arm Type
Experimental
Arm Description
75 mg LY3295668 BID administered orally in 21-day cycles.
Arm Title
25 mg LY3295668 (Phase 2)
Arm Type
Experimental
Arm Description
25 mg LY3295668 BID administered orally in 21-day cycles.
Intervention Type
Drug
Intervention Name(s)
LY3295668
Other Intervention Name(s)
AK-01, Erbumine
Intervention Description
Oral capsules
Primary Outcome Measure Information:
Title
Phase 1: Maximum Tolerated Dose
Description
Maximum Tolerated Dose (MTD) was defined as the dose immediately below the dose at which ≥2/3, ≥2/6, or ≥3/9 participants in a cohort experienced a dose limiting toxicity (DLT) during the first 21 days of treatment (Cycle 1) in Phase 1.
Time Frame
Cycle 1 (21 days)
Title
Phase 2: Percentage of Participants Who Achieved Partial Response (PR) or Complete Response (CR) [Objective Response Rate (ORR)]
Description
Objective response rate (ORR) was defined as a percentage of responders who achieved complete response or partial response (CR+PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1). Complete response (CR) is defined as disappearance of all target (and non-target) lesions, and no appearance of new lesion. Partial response (PR) was defined as at least a 30% decrease in the sum of longest diameters (LD) of target lesions, taking as reference the baseline sum of LD, no progression of non-target lesions, and no appearance of new lesions.
Time Frame
Baseline to Objective Disease Progression (Up to 11 months)
Secondary Outcome Measure Information:
Title
Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events
Description
A treatment-emergent adverse event (AE) is an AE that started or worsened (increased in severity) from the treatment start date to 30 days after the treatment end date. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
Time Frame
Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
Title
Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events
Description
A treatment-emergent adverse event (AE) is an AE that started or worsened (increased in severity) from the treatment start date to 30 days after the treatment end date. A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
Time Frame
Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
Title
Phase 2: Pharmacokinetic (PK): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC[0-12]) (Phase 2)
Description
Area under the plasma concentration-time curve for LY3295668 from time zero to 12 hours.
Time Frame
Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 - 12 hours postdose; Cycle 1: Day 2 and Day 8 predose
Title
Phase 2: PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC[0-24])
Description
Area under the plasma concentration-time curve for LY3295668 from time zero to 24 hours.
Time Frame
Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8-12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose
Title
Phase 2: PK: Maximum Observed Plasma Concentration (Cmax)
Description
Maximum observed plasma concentration for LY3295668.
Time Frame
Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose
Title
Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax)
Description
Time of maximum observed plasma concentration of LY3295668.
Time Frame
Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose
Title
Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2)
Description
Apparent terminal elimination half-life of LY3295668.
Time Frame
Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8-12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose
Title
Phase 2: PK: Apparent Total Plasma Clearance (CL/F)
Description
Apparent total plasma clearance of LY3295668.
Time Frame
Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 -12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose
Title
Phase 2: PK: Apparent Volume of Distribution (Vz/F)
Description
Apparent volume of distribution of LY3295668.
Time Frame
Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 -12 hours post-dose; Cycle 1: Day 2 and Day 8 Predose
Title
Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 White Blood Cell Count (WBC)
Description
Presented are participants with the worst post-baseline WBC Grade >= 3 using the National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events version 4.03 (CTCAE v4.03). where Grade 1: < Lower Limit Normal (LLN) - 3000/mm3; <LLN - 3.0 x10e9/L, Grade 2: <3000 - 2000/mm3; <3.0 - 2.0 x10e9/L, Grade 3: <2000 - 1000/mm3; <2.0 1.0 x10e9/L, Grade 4: <1000/mm3; <1.0 x10e9/L.
Time Frame
Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
Title
Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Neutrophils (Segmented and Blended)
Description
Presented are participants with the worst post-baseline neutrophils Grade >=3 using the NCI-CTCAE v4.03 where Grade 1: < LLN - 1500/mm3; <LLN - 1.5 x10e9/L, Grade 2: <1500 - 1000/mm3; <1.5 - 1.0 x10e9/L, Grade 3: <1000 - 500/mm3; <1.0 - 0.5 x10e9/L, Grade 4: <500/mm3; <0.5 x 10e9/L.
Time Frame
Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
Title
Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Lymphocytes
Description
Presented are participants with the worst post-baseline lymphocytes Grade >=3 using the NCI-CTCAE version 4.03 where Grade 1: <LLN - <800/mm3, <LLN - 0.8 x 10e9/L, Grade 2: <800 - 500/mm3; <0.8 - 0.5 x 10e9/L, Grade 3: <500 - 200/mm3; <0.5 - 0.2 x 10e9/L, <200mm3; <0.2 x 10e9/L.
Time Frame
Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have received at least 1 but no more than 4 prior systemic therapies
Have adequate organ function
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
Have estimated life expectancy greater than or equal to (≥)12 weeks
Have fully recovered from radiation therapy or surgery, and are recovering from any acute adverse effects of other cancer therapies
Have discontinued all chemotherapy, investigational therapy, molecularly-targeted therapy, and cancer-related hormonal therapy at least 14 days prior, biologic or immunotherapeutic therapy at least 21 days prior, or mitomycin-C or nitrosoureas at least 6 weeks prior
Female participants with reproductive potential agree to use 2 forms of highly effective contraception during the study and for the following 3 months
Male participants must use a barrier method of contraception during the study and for the following 3 months
Phase 1
Have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor)
Phase 2
Have disease measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1
Have evidence of a solid tumor that is locally advanced and/or metastatic, and in:
Small Cell Lung Cancer (SCLC), must have failed platinum-containing therapy
Breast Cancer, be Estrogen Receptor positive and/or Progesterone Receptor positive, but Human Epidermal Growth Factor Receptor 2 (HER2) negative, and must have failed a hormone therapy and a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor
Triple negative breast cancer (TNBC) and failed standard therapy
Squamous cell cancers of the head neck associated with the human papilloma virus (HPV), and have failed standard therapy
Other solid tumor type that has been approved by the sponsor
Exclusion Criteria:
Have symptomatic central nervous system (CNS) metastasis (unless asymptomatic and not current receiving corticosteroids) or a primary tumor of the CNS
Have a medical condition that precludes participation (swallowing disorder, organ transplant, pregnant or nursing, HIV, active Hepatitis B or C, cardiac disease, history of major surgery in upper gastrointestinal (GI) tract or GI disease, hypokalemia, hypomagnesaemia or hypocalcaemia that cannot be controlled)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
McGill University
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
IPD Sharing Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing URL
https://vivli.org/
Citations:
PubMed Identifier
33479856
Citation
Chu QS, Bouganim N, Fortier C, Zaknoen S, Stille JR, Kremer JD, Yuen E, Hui YH, de la Pena A, Lithio A, Smith PS, Batist G. Aurora kinase A inhibitor, LY3295668 erbumine: a phase 1 monotherapy safety study in patients with locally advanced or metastatic solid tumors. Invest New Drugs. 2021 Aug;39(4):1001-1010. doi: 10.1007/s10637-020-01049-3. Epub 2021 Jan 22.
Results Reference
derived
Learn more about this trial
A Study of AK-01 (LY3295668) in Solid Tumors
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