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

NCT05017025 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2021-0240NCI-2021-08752
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Stage III Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8; Stage IIIA Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Advanced Lung Non-Squamous Non-Small Cell Carcinoma; Metastatic Lung Non-Squamous Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity and recommended phase 2 dose

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

  Up to 30 days after last dose

Secondary Outcomes (3)

• Progression-free survival

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

• Best objective response rate

  Within 6 months after treatment

• Overall survival

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

Study Arms (1)

Treatment (osimertinib, aurora A kinase inhibitor LY3295668)

EXPERIMENTAL

Patients 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.

Drug: Aurora A Kinase Inhibitor LY3295668; Drug: Osimertinib

Interventions

Aurora A Kinase Inhibitor LY3295668 DRUG

Given PO

Also known as: AK 01, AK-01, LY 3295668, LY-3295668, LY3295668

Treatment (osimertinib, aurora A kinase inhibitor LY3295668)

Osimertinib DRUG

Given PO

Also known as: AZD-9291, AZD9291, Mereletinib, Tagrisso

Treatment (osimertinib, aurora A kinase inhibitor LY3295668)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Lung Neoplasms

Interventions

LY3295668 erbumine; osimertinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Xiuning Le

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: August 23, 2021
• Study Start: February 17, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)