Clinical trial NCT03092934: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neoplasms
Neoplasm Metastasis
Triple Negative Breast Neoplasms
Head and Neck Neoplasms
Breast Neoplasms
Solid Tumor, Adult
Small Cell Lung Carcinoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: AurKa Pharma Inc.
First posted: 2017-03-28
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Phase 1: Maximum Tolerated Dose
timeFrame: Cycle 1 (21 days)
measure: Phase 2: Percentage of Participants Who Achieved Partial Response (PR) or Complete Response (CR) [Objective Response Rate (ORR)]
timeFrame: Baseline to Objective Disease Progression (Up to 11 months)
Secondary outcomes:
measure: Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events
timeFrame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
measure: Phase 2: Number of Participants With One or More Treatment-Emergent Adverse Events
timeFrame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
measure: Phase 2: Pharmacokinetic (PK): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose (AUC[0-12]) (Phase 2)
timeFrame: 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
measure: Phase 2: PK: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours Post-dose (AUC[0-24])
timeFrame: 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
measure: Phase 2: PK: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose
measure: Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose
measure: Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2)
timeFrame: 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
measure: Phase 2: PK: Apparent Total Plasma Clearance (CL/F)
timeFrame: 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
measure: Phase 2: PK: Apparent Volume of Distribution (Vz/F)
timeFrame: 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
measure: Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 White Blood Cell Count (WBC)
timeFrame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
measure: Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Neutrophils (Segmented and Blended)
timeFrame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
measure: Phase 1: Number of Participants With Worst Post-Baseline Grade >=3 Lymphocytes
timeFrame: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
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.