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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Breast Neoplasms; Head and Neck Neoplasms; Small Cell Lung Carcinoma; Neoplasm Metastasis; Triple Negative Breast Neoplasms; Solid Tumor, Adult
• Intervention / Treatment: Drug: LY3295668

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Cycle 1 (21 days)
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.	Baseline to Objective Disease Progression (Up to 11 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
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.	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
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.	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
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.	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
Phase 2: PK: Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration for LY3295668.	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose
Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax)	Time of maximum observed plasma concentration of LY3295668.	Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose
Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2)	Apparent terminal elimination half-life of LY3295668.	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
Phase 2: PK: Apparent Total Plasma Clearance (CL/F)	Apparent total plasma clearance of LY3295668.	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
Phase 2: PK: Apparent Volume of Distribution (Vz/F)	Apparent volume of distribution of LY3295668.	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
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.	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
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.	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
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.	Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: AurKa Pharma Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 29, 2017
• Primary Completion (ACTUAL): April 20, 2020
• Study Completion (ACTUAL): April 20, 2020

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: March 22, 2017
• First Posted (ACTUAL): March 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 2, 2021
• Last Update Submitted That Met QC Criteria: June 29, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Breast Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Lung Neoplasms; Neoplasms; Breast Neoplasms; Head and Neck Neoplasms; Neoplasm Metastasis; Small Cell Lung Carcinoma; Triple Negative Breast Neoplasms
• Other Study ID Numbers: 17228; AURA-001 (OTHER: AurKa Pharma Inc.); J1O-MC-JZHA (OTHER: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No