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Advanced Lung Non-Squamous Non-Small Cell CarcinomaPhase 1/2NCT05017025

Aurora Kinase Inhibitor LY3295668 in Combination With Osimertinib for the Treatment of Advanced or Metastatic EGFR-Mutant Non-squamous Non-small Cell Lung Cancer

A Phase 1/2 study testing Aurora A Kinase Inhibitor LY3295668 and Osimertinib in people with Advanced Lung Non-Squamous Non-Small Cell Carcinoma and Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

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 phase Ib/II trial studies the side effects and best dose of aurora A kinase inhibitor LY3295668 when given together with osimertinib in patients with EGFR-mutant non-squamous non-small cell lung cancer that has spread to other places in the body (advanced or metastatic). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Aurora A Kinase Inhibitor LY3295668 and Osimertinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
17 Feb 2022to 15 Sep 2026
Phase
Phase 1/2

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

  • Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent.
  • Age ≥ 18 years at the time of consent.
  • Histologically or cytologically confirmed non-squamous, non-small cell lung cancer
  • Locally advanced or metastatic disease.
  • Patients must have one of the following:
  • NSCLC which harbours EGFR Exon 19 deletion.
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  • NSCLC which harbours EGFR L858R mutation. EGFR deletion/mutation must be documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test (either from tissue or ctDNA from blood is allowed)
  • The patient must have received a third-generation EGFR TKI treatment, regardless of the T790M status. The patient must have progressed on osimertinib, or an equivalent third-generation EGFR TKI with regulatory approval.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix A)
  • At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline at equal or greater than 10mm in the longest dimension by RECIST 1.1.
  • Ability to take pills or capsules by mouth
  • Prior treatment with cytotoxic chemotherapy or immunotherapy is allowed. Up to 3 lines of prior therapy is allowed.
  • Patients must have adequate hematologic, coagulation, hepatic, and renal function. All laboratory tests must be obtained less than 4 weeks from study entry. This includes:
  • ANC >/= 1,500/mm3
  • platelet count >/=100,000/mm3
  • HgB ≥ 9 g/dL
  • Creatinine ≤ 1.5x ULN or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is >1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed).
  • Total Serum Bilirubin ≤ 1.5 x ULN (Patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)
  • SGOT, SGPT ≤ 3 X ULN if no liver metastasis present
  • SGOT, SGPT ≤ 5 X ULN if liver metastasis present
  • Females of childbearing potential must not be breast feeding and must have a negative serum or urine pregnancy test within 7 days of starting of treatment. The patient must agree to use adequate contraception for a minimum of two weeks prior to receiving study medication until 3 months after discontinuation of the study medication. Acceptable methods of contraception include total and true sexual abstinence, hormonal contraceptives that are not prone to drug-drug interactions (IUS Levonorgestrel Intra Uterine System (Mirena), Medroxyprogesterone injections (Depo-Provera)), copper-banded intra-uterine devices, and vasectomized partner. All hormonal methods of contraception should be used in combination with the use of a condom by their sexual male partner. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause. The following age-specific requirements must also apply: Women < 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) must also be in the post-menopausal range (as per the institution). Women ≥ 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses > 1 year ago, or have had chemotherapy-induced menopause with >1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy.
  • Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study and 3 months after the last dose of study medication. Adequate contraception methods include: birth control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom plus spermicide, cervical/vault cap or intrauterine device), and abstinence. Patients should not father a child for 6 months after completion of the study medication. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing the study medication. If male patients wish to father children they should be advised to arrange for freezing of sperm samples prior to the start of the study medication.
  • Participants of childbearing potential who are sexually active and their partners must agree to abstain from heterosexual activity or to use 2 forms of effective methods of contraception. Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study and for 3 months after the last dose of study treatment. Patients should not father a child during the study or for 6 months after completion of study treatment. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing the study treatment. Two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. See below for options:
  • Acceptable non-hormonal birth control methods:
  • Total sexual abstinence ie, refrain from any form of sexual intercourse in line with the patients' usual and/or preferred lifestyle. Abstinence must be for the total duration as described above. Periodic abstinence (eg, calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Vasectomised sexual partner PLUS male condom. With participant assurance that partner received post-vasectomy confirmation of azoospermia.
  • Tubal occlusion PLUS male condom
  • Intrauterine Device PLUS male condom. Provided coils are copper-banded.
  • Acceptable hormonal methods:
  • Etonogestrel implants (eg, Implanon®, Norplant®) PLUS male condom
  • Normal and low dose combined oral pills PLUS male condom
  • Hormonal shot or injection (eg, Depo-Provera) PLUS male condom
  • Intrauterine system device (eg, levonorgestrel-releasing intrauterine system - Mirena®) PLUS male condom

Who cannot join

  • Previous treatment with other aurora kinase inhibitors.
  • Spinal cord compression or brain metastases unless asymptomatic or stable for at least 2 weeks prior to start of study treatment.
  • Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the exception of alopecia grade 2) at the time of starting study treatment.
  • Any evidence of severe or uncontrolled systemic diseases. Screening for chronic conditions is not required.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
  • Males and females of reproductive potential who are not using and effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry.
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  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirement.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc using Fridericia's formula) > 470 msec, except in patients with existing bundle block, which artificially prolongs QTc.
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250msec
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval.
  • The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy.
  • The patient has uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase Ib/II Trial to Evaluate Safety, Tolerability and Efficacy of Aurora Kinase Inhibitor LY3295668 in Combination With Osimertinib for Patients With EGFR-Mutant Non-Small Cell Lung Cancer

This phase Ib/II trial studies the side effects and best dose of aurora A kinase inhibitor LY3295668 when given together with osimertinib in patients with EGFR-mutant non-squamous non-small cell lung cancer that has spread to other places in the body (advanced or metastatic). Aurora A kinase inhibitor LY3295668 and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving aurora A kinase inhibitor LY3295668 in combination with osimertinib may help control EGFR-mutant non-squamous non-small cell lung cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate dose-limiting toxicity (DLT) and to establish the recommended phase II dose (RP2D) of aurora A kinase inhibitor LY3295668 (LY3295668) given in combination with osimertinib in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC).

II. To preliminarily assess efficacy of LY3295668 plus osimertinib in advanced EGFR-mutant NSCLC who progressed on prior EGFR tyrosine kinase inhibitor (TKI). The co-primary endpoints are progression-free survival (PFS) at 6 months after treatment and best objective response rate (BRR) within 6 months after treatment.

SECONDARY OBJECTIVES:

  1. Determine the objective response rate (ORR) with osimertinib LY3295668 combination.

II. Determine the overall survival (OS) with osimertinib LY3295668 combination. III. Determine the disease control rate (DCR) with osimertinib LY3295668 combination.

IV. Determine the safety and tolerability with osimertinib LY3295668 combination.

CORRELATIVE/EXPLORATORY OBJECTIVES:

  1. Explore the association of baseline genomic profiles (from tumor, germline deoxyribonucleic acid [DNA], and circulating tumor [ct]DNA) with clinical benefit in patients treated with osimertinib LY3295668 combination.

II. Explore resistance mechanisms to osimertinib LY3295668 combination. III. Determine the immunomodulatory effects of osimertinib LY3295668 combination.

OUTLINE:

Patients receive osimertinib orally (PO) once daily (QD) and aurora A kinase inhibitor LY3295668 PO twice daily (BID) on days 1-28. Treatment repeats every 28 days for 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 4 months thereafter.

Being tested
Aurora A Kinase Inhibitor LY3295668, Osimertinib
Medical subject headings
Lung Neoplasms

What participants receive

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

  • Aurora A Kinase Inhibitor LY3295668Drug

    Also called AK 01, AK-01, LY 3295668, LY-3295668

    Given PO

  • OsimertinibDrug

    Also called AZD-9291, AZD9291, Mereletinib, Tagrisso

    Given PO

Study groups in NCT05017025
Study groupRoleWhat they receive
Treatment (osimertinib, aurora A kinase inhibitor LY3295668)ExperimentalPatients receive osimertinib PO QD and aurora A kinase inhibitor LY3295668 PO BID on days 1-28. Treatment repeats every 28 days for 24 cycles (2 years) in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Aurora A Kinase Inhibitor LY3295668; Drug: Osimertinib

What is being measured

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

  1. Dose-limiting toxicity and recommended phase 2 dose

    Adverse event data will be summarized by type and severity grade.

    Measured: Up to 30 days after last dose

Secondary outcomes (3)

  1. Progression-free survival

    Will be estimated using the method of Kaplan and Meier. Will be provided with 95% confidence intervals.

    Measured: Date of treatment started until the criteria for disease progression is met, assessed at 6 months after treatment

  2. Best objective response rate

    Will be provided with 95% confidence intervals.

    Measured: Within 6 months after treatment

  3. Overall survival

    Measured: Date of treatment started to date of death from any cause, assessed at 6 months after treatment

Timeline

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

  1. First posted23 Aug 2021
  2. Study start17 Feb 2022
  3. Primary completion15 Sep 2026
  4. Study completion15 Sep 2026

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05017025
Sponsor's protocol ID
2021-0240
Other IDs
NCI-2021-08752, 2021-0240
Status last verified
Sep 2026
First submitted
17 Aug 2021
Last updated
18 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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