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NCT Number: NCT03092934

A Study of AK-01 (LY3295668) in 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.

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Key information

Conditions

Neoplasms Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Head and Neck Neoplasms Lung Diseases Lung Neoplasms Neoplasm Metastasis Neoplasms by Site Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin and Connective Tissue Diseases Small Cell Lung Carcinoma Solid Tumor, Adult Thoracic Neoplasms Triple Negative Breast Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Cross Cancer Institute, Edmonton, Alberta, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

LY3295668

Drug

Oral capsules

Other names: AK-01, Erbumine

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Collaborators

  • AurKa Pharma Inc.

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Mar 28, 2017
Registry last updated
Jul 2, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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