Phase II Study of Osimertinib (AZD9291) in Advanced NSCLC Patients With Exon 20 Insertion Mutations in EGFR

Plain English Summary

Testing Osimertinib as a Treatment for Lung Cancers With an EGFR Exon 20 Change is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Advanced Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Stage IV Lung Non-Small Cell Cancer AJCC v7. This trial tests a drug called osimertinib for advanced non-small cell lung cancer (NSCLC) with a specific genetic change (EGFR exon 20 insertion). It is for adults with this type of lung cancer who have already received at least one prior treatment for advanced disease. Participation involves taking the study drug, undergoing regular medical tests, and having tumor tissue tested for the specific genetic mutation. Standard chemotherapy or other targeted therapies are current alternatives for this type of lung cancer. The trial aims to enroll 46 participants.

Official Summary

This phase II trial studies how well osimertinib works in treating patients with non-small cell lung cancer with EGFR exon 20 insertion mutation that is stage IIIB-IV or has come back after a period of improvement (recurrent). Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with a confirmed diagnosis of advanced non-small cell lung cancer. Patients must have a specific genetic mutation called an EGFR exon 20 insertion in their tumor. Individuals must have received at least one prior treatment for their advanced lung cancer and not have received osimertinib before. Participants must have good general health, with specific requirements for blood counts, organ function, and no active or symptomatic lung disease. This trial is studying Advanced Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Stage IV Lung Non-Small Cell Cancer AJCC v7, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how well the drug shrinks tumors, which means patients may experience a reduction in cancer size and potentially a slowing of disease progression. The specific primary outcome measures are: Best objective response (Up to 5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for effective treatments for lung cancer patients with EGFR exon 20 insertion mutations, a group for whom current targeted therapies are often less effective. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Advanced Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Stage IV Lung Non-Small Cell Cancer AJCC v7, where improved treatment options are needed.

Investor Insight

This trial targets a niche but important subset of lung cancer patients, indicating potential for a new treatment option in a market with unmet needs, though the specific market size for this mutation Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if your lung cancer has an EGFR exon 20 insertion mutation and if this trial is a good fit for you. Be prepared for regular clinic visits for drug administration, blood tests, imaging scans, and to report any side effects. The study involves taking osimertinib daily and undergoing various medical assessments throughout the trial. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 46 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo collection of blood samples
• PROCEDURE: Computed Tomography with Contrast — Undergo CT with contrast
• PROCEDURE: Echocardiography Test — Undergo ECHO
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI
• PROCEDURE: Multigated Acquisition Scan — Undergo MUGA

Primary Outcomes

• Best objective response (Up to 5 years)

Secondary Outcomes

• Progression-free survival (PFS) (From registration to documented disease progression or death from any cause, whichever occurs first, assessed up to 5 years)
• Overall survival (OS) (From registration to death from any cause, assessed up to 5 years)
• Incidence of adverse events (Up to 5 years)

Full Eligibility Criteria

Inclusion Criteria:

* Participants must have a pathologically-confirmed diagnosis of non-small cell lung cancer (NSCLC)
* Participants must have advanced disease - either stage IV disease, stage IIIB disease not amenable to definitive multi-modality therapy, or recurrent disease after a prior diagnosis of stage I-III disease. All staging is via the American Joint Committee on Cancer (AJCC)/International Association for the Study of Lung Cancer (IASLC) 7th edition staging criteria
* An EGFR exon 20 insertion mutation must be detected in the tumor tissue. Patients may be enrolled in the study based on an exon 20 insertion EGFR mutation detected by any Clinical Laboratory Improvement Act (CLIA)-certified tissue assay

  * NOTE: Testing results are to be submitted via Medidata Rave and the study chair or delegate will review the reports
* Patients must have measurable disease; baseline measurements and ALL sites of disease must be obtained within 4 weeks to registration
* Patients must have previously received at least one line of therapy for their advanced lung cancer; there are no restrictions on the maximum number of prior therapies allowed
* Participants must not have previously received osimertinib
* Participants must have not previously received therapies targeting PDL1, PD1 or CTLA4 within 6 months (180 days) prior to registration
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
* Hemoglobin \>= 9.0 g/L (within 4 weeks before registration)
* Leukocytes/white blood cells \>= 3,000/mcL (within 4 weeks before registration)
* Absolute neutrophil count \>= 1,500/mcL (within 4 weeks before registration)
* Platelets \>= 100,000/mcL (within 4 weeks before registration)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) if no liver metastases or =\< 3 times ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases (within 4 weeks before registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal; for patients with known hepatic metastases AST and/or ALT =\< 5 x ULN (within 4 weeks before registration)
* Creatinine =\< 1.5 x institutional upper limit of normal (within 4 weeks before registration)
* Participants may not have clinically active or symptomatic interstitial lung disease or interstitial pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention), or a history of clinically significant interstitial lung disease or radiation pneumonitis
* Participants may not have had radiation to the lung fields within four weeks (28 days) of starting treatment. For patients receiving palliative radiation to thoracic vertebrae, ribs or other sites where the radiation field includes the lungs, radiation must be completed at least two weeks before starting treatment. For all palliative radiation to all other sites, at least 7 days must have elapsed prior to starting treatment. At least six months (180 days) must have elapsed prior to starting treatment for radiation given with curative intent. Palliative radiotherapy to control symptoms (including gamma knife technique) is permitted. For stereotactic radiosurgery (SRS) to central nervous system (CNS) lesions, osimertinib can be held on the day of radiation only. For palliative radiotherapy (RT) to other sites of disease outside of the thorax osimertinib (osi) should be held for a minimum of 3 days before radiation and 3 days after RT is completed, but the duration of washout can be adjusted at the investigator's discretion with the approval of the study principal investigator (PI). For thoracic radiation, a 7-10 day washout period before the procedure and one week period after procedure before restarting osimertinib is advised to minimize the risk of pneumonitis. All radiotherapy related toxicities should be managed and ideally resolved before restarting osimertinib. Investigators should consider the radiotherapy when assessing causality if there are any localized adverse events (AEs) following the procedure
* Participants may not have clinically symptomatic brain metastases, leptomeningeal disease, or spinal cord compression. Patients may be on a stable dose of corticosteroids to control brain metastases if they have been on a stable dose for two weeks (14 days) prior to study treatment and are clinically asymptomatic
* Patients must have an ECHO or a nuclear study (MUGA or first pass) within 4 weeks (28 days) prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) \< institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be \>= 50% for the patient to be eligible
* Participants may not have any of the following cardiac criteria:

  * Mean resting corrected QT interval (QTc) \>= 470 msec obtained from 3 ele

Trial Locations

• Anchorage Associates in Radiation Medicine, Anchorage, Alaska, United States
• Anchorage Radiation Therapy Center, Anchorage, Alaska, United States
• Alaska Breast Care and Surgery LLC, Anchorage, Alaska, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Alaska Women's Cancer Care, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Mercy Hospital Fort Smith, Fort Smith, Arkansas, United States
• CARTI Cancer Center, Little Rock, Arkansas, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer
• Adenocarcinoma of Lung
• EGFR Mutation
• Targeted Cancer Therapy
• Oncology
• Thoracic Oncology
• Metastatic Lung Cancer
• Recurrent Lung Cancer
• Advanced Solid Tumors

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