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NeoplasmsPhase 1/2NCT03092934

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

A Phase 1/2 study testing LY3295668 in people with Neoplasms and Neoplasm Metastasis, run by Eli Lilly and Company at 3 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LY3295668
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
3 sitesCanada
Study dates
29 May 2017to 20 Apr 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 18Show fewer
  • 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

Who cannot join

  • 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)

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • McGill University

    Montreal, Quebec, H4A 3J1

Other trials in Canada

About this study

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

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.

Being tested
LY3295668
Medical subject headings
Neoplasms, Neoplasm Metastasis, Triple Negative Breast Neoplasms, Head and Neck Neoplasms, Breast Neoplasms, Small Cell Lung Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LY3295668Drug

    Also called AK-01, Erbumine

    Oral capsules

Study groups in NCT03092934
Study groupRoleWhat they receive
25 milligrams (mg) LY3295668 (Phase 1)Experimental25 milligrams (mg) LY3295668 twice daily (BID) administered orally in 21-day cycles.
Receives: Drug: LY3295668
50 mg LY3295668 (Phase 1)Experimental50 mg LY3295668 BID administered orally in 21-day cycles.
Receives: Drug: LY3295668
75 mg LY3295668 (Phase 1)Experimental75 mg LY3295668 BID administered orally in 21-day cycles.
Receives: Drug: LY3295668
25 mg LY3295668 (Phase 2)Experimental25 mg LY3295668 BID administered orally in 21-day cycles.
Receives: Drug: LY3295668

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Cycle 1 (21 days)

  2. 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.

    Measured: Baseline to Objective Disease Progression (Up to 11 months)

Secondary outcomes (12)

  1. 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.

    Measured: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

  2. 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.

    Measured: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

  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)

    Area under the plasma concentration-time curve for LY3295668 from time zero to 12 hours.

    Measured: 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

  4. 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.

    Measured: 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

  5. Phase 2: PK: Maximum Observed Plasma Concentration (Cmax)

    Maximum observed plasma concentration for LY3295668.

    Measured: Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose

  6. Phase 2: PK: Time of Maximum Observed Plasma Concentration (Tmax)

    Time of maximum observed plasma concentration of LY3295668.

    Measured: Cycle 1: Day 1 and Day 15: Predose, 1, 2, 4, 6, and 8 hours post-dose

  7. Phase 2: PK: Apparent Terminal Elimination Half-life (t1/2)

    Apparent terminal elimination half-life of LY3295668.

    Measured: 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

  8. Phase 2: PK: Apparent Total Plasma Clearance (CL/F)

    Apparent total plasma clearance of LY3295668.

    Measured: 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

  9. Phase 2: PK: Apparent Volume of Distribution (Vz/F)

    Apparent volume of distribution of LY3295668.

    Measured: 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

  10. 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.

    Measured: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

  11. 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.

    Measured: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

  12. 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.

    Measured: Cycle 1 Day 1 through 30 Days After Treatment End Date (Up to 29 Months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2017
  2. Study start29 May 2017
  3. Primary completion20 Apr 2020
  4. Study completion20 Apr 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03092934
Sponsor's protocol ID
17228
Other IDs
AURA-001, J1O-MC-JZHA
Status last verified
Jun 2021
First submitted
22 Mar 2017
Last updated
2 Jul 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

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.

    PubMed 33479856

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LY3295668 in people with Neoplasms and Neoplasm Metastasis, run by Eli Lilly and Company at 3 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Maximum Tolerated Dose (time frame: Cycle 1 (21 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03092934, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2021.

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