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A Study of AK-01 (LY3295668) in Solid Tumors

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ClinicalTrials.gov Identifier: NCT03092934
Recruitment Status : Completed
First Posted : March 28, 2017
Results First Posted : July 2, 2021
Last Update Posted : July 2, 2021
Sponsor:
Collaborator:
AurKa Pharma Inc.
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Neoplasms Neoplasm Metastasis Triple Negative Breast Neoplasms Head and Neck Neoplasms Breast Neoplasms Solid Tumor, Adult Small Cell Lung Carcinoma Drug: LY3295668 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: Open-Label
Primary Purpose: Treatment
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
Actual Study Start Date : May 29, 2017
Actual Primary Completion Date : April 20, 2020
Actual Study Completion Date : April 20, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 25 milligrams (mg) LY3295668 (Phase 1)
25 milligrams (mg) LY3295668 twice daily (BID) administered orally in 21-day cycles.
Drug: LY3295668
Oral capsules
Other Names:
  • AK-01
  • Erbumine

Experimental: 50 mg LY3295668 (Phase 1)
50 mg LY3295668 BID administered orally in 21-day cycles.
Drug: LY3295668
Oral capsules
Other Names:
  • AK-01
  • Erbumine

Experimental: 75 mg LY3295668 (Phase 1)
75 mg LY3295668 BID administered orally in 21-day cycles.
Drug: LY3295668
Oral capsules
Other Names:
  • AK-01
  • Erbumine

Experimental: 25 mg LY3295668 (Phase 2)
25 mg LY3295668 BID administered orally in 21-day cycles.
Drug: LY3295668
Oral capsules
Other Names:
  • AK-01
  • Erbumine




Primary Outcome Measures :
  1. Phase 1: Maximum Tolerated Dose [ Time Frame: Cycle 1 (21 days) ]
    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.

  2. Phase 2: Percentage of Participants Who Achieved Partial Response (PR) or Complete Response (CR) [Objective Response Rate (ORR)] [ Time Frame: Baseline to Objective Disease Progression (Up to 11 months) ]
    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 :
  1. Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events [ Time Frame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months) ]
    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.

  2. Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events [ Time Frame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months) ]
    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.

  3. Phase 2: Pharmacokinetic (PK): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC[0-12]) (Phase 2) [ 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 ]
    Area under the plasma concentration-time curve for LY3295668 from time zero to 12 hours.

  4. Phase 2: PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC[0-24]) [ 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 ]
    Area under the plasma concentration-time curve for LY3295668 from time zero to 24 hours.

  5. Phase 2: PK: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose ]
    Maximum observed plasma concentration for LY3295668.

  6. Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose ]
    Time of maximum observed plasma concentration of LY3295668.

  7. Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2) [ 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 ]
    Apparent terminal elimination half-life of LY3295668.

  8. Phase 2: PK: Apparent Total Plasma Clearance (CL/F) [ 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 ]
    Apparent total plasma clearance of LY3295668.

  9. Phase 2: PK: Apparent Volume of Distribution (Vz/F) [ 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 ]
    Apparent volume of distribution of LY3295668.

  10. Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 White Blood Cell Count (WBC) [ Time Frame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months) ]
    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.

  11. Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Neutrophils (Segmented and Blended) [ Time Frame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months) ]
    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.

  12. Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Lymphocytes [ Time Frame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03092934


Locations
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Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
McGill University
Montreal, Quebec, Canada, H4A 3J1
Sponsors and Collaborators
Eli Lilly and Company
AurKa Pharma Inc.
Investigators
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Study Director: 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 Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] April 10, 2018
Statistical Analysis Plan  [PDF] February 6, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03092934    
Other Study ID Numbers: 17228
AURA-001 ( Other Identifier: AurKa Pharma Inc. )
J1O-MC-JZHA ( Other Identifier: Eli Lilly and Company )
First Posted: March 28, 2017    Key Record Dates
Results First Posted: July 2, 2021
Last Update Posted: July 2, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Neoplasm Metastasis
Breast Neoplasms
Head and Neck Neoplasms
Small Cell Lung Carcinoma
Triple Negative Breast Neoplasms
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Breast Diseases
Skin Diseases
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms