Phase 2 N=37 Treatment

Local Ablative Therapy for Treatment of Oligoprogressive, EGFR-Mutated, Non-Small Cell Lung Cancer After Treatment With Osimertinib

Lung Adenocarcinoma · Lung Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT02759835 ↗

Enrolled (actual)

Serious AEs

56.8%

Results posted

Jul 2023

Primary outcome: Primary: Progression Free Survival 1 (PFS 1) for ALL Participants Who Started Osimertinib on Trial Until First Progression of Disease or Clinical Progression, or Death Any Cause — 14.7; 11.0 Months — p=0.56

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: osimertinib (Drug); Local Ablative Therapy (LAT) (Other)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: May 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Progression Free Survival 1 (PFS 1) for ALL Participants Who Started Osimertinib on Trial Until First Progression of Disease or Clinical Progression, or Death Any Cause	14.7; 11.0	0.56
PRIMARY Progression Free Survival 2 (PFS 2) - Local Ablative Therapy (LAT Eligible Only)	3.7	—
PRIMARY Progression Free Survival 2 (PFS 2) - Local Ablative Therapy (LAT Eligible Only) - Cohort 1, Cohort 2, and Cohort 3	4.0; 3.6; 3.7	0.40
PRIMARY Serious Adverse Events Possibly, Probably, and/or Definitely Related to Treatment	1; 0; 0; 1; 0; 0	—
PRIMARY All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)	1; 0; 0; 0; 0; 0	—
PRIMARY All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib	1; 1; 0; 1; 0; 0	—
PRIMARY Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors	9; 3; 3; 8; 2; 2	—
PRIMARY Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment	1; 0; 0; 1; 0; 0	—
SECONDARY Best Overall Response (BOR)	70.8; 66.7; 0.0; 0.0; 0.0	—
SECONDARY Best Overall Response - All Participants	69.7; 0.0	—
SECONDARY Overall Survival	38.2; 33.7	—
SECONDARY Disease Control Rate (DCR)	100; 100; 66.7; 50.0; 100	—
SECONDARY Disease Control Rate (DCR) - All Participants	100; 66.7	—

Summary

Background: Some non-small-cell lung cancers (NSCLC) have a mutation in a gene that makes a protein called EGFR. This particular cancer can be treated with certain drugs such as erlotinib (Tarceva), gefitinib (Iressa) and osimertinib (Tagrisso). But many tumors become resistant to these drugs because of a second mutation. Researchers want to test if adding local ablative therapy (LAT) extends the benefits of the drug, osimertinib. LAT can include techniques such as surgery, radiofrequency ablation, cryotherapy or radiation therapy. Objective: To test if re-taking osimertinib after LAT is safe, tolerable, and effective for people whose NSCLC has progressed after initial treatment with osimertinib. Eligibility: Adults ages 18 and older with certain types of NSCLC. Participants will be divided into various groups as described below. Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Tumor scans Eye exam Review of tumor sample. Participants will take the study drug by mouth once a day. They will continue until they can no longer tolerate it or their disease worsens. They will keep a dosage diary. All participants will start each 21-day course with physical exam; blood, urine, and saliva tests; and electrocardiogram. They will have scans every 6 weeks and echocardiogram every 3 months. Groups 1 and 2 will: Start osimertinib right away. Have LAT if their disease progresses and is suitable for LAT. If LAT cannot be performed or LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Re-start osimertinib after LAT, or other treatments if not suitable for LAT. Group 3 will: Have LAT. If LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Start osimertinib after LAT. After participants stop taking the drugs, they will have a final visit. This will include: Medical history Physical exam Blood tests Participants will be called every year for follow-up.

Eligibility Criteria

INCLUSION CRITERIA:

For inclusion in the study subjects should fulfill the following criteria:

Provision of informed consent prior to any study specific procedures
Patients (male/female) must be greater than or equal to 18 years of age.
Patients with histologically confirmed, by the National Cancer Institute (NCI) Laboratory of Pathology or by Clinical Laboratory Improvement Amendments of 1988 (CLIA)-certified Next Generation Sequencing or Cobas estimated Epidermal Growth Factor Receptor (EGFR) Mutation Test v1/2 at an outside institution, advanced lung adenocarcinoma with EGFR-sensitizing somatic mutations or a germline T790M mutation (detected histologically or via circulating tumor deoxyribonucleic acid (ctDNA) analysis using a CLIA assay) with:
No prior EGFR tyrosine kinase inhibitor (TKI) therapy (Cohort 1)

-- Progressive disease after 1st or 2nd generation EGFR TKI therapy harboring somatic T790M mutation (Cohort 2)

Progressive disease after treatment with osimertinib who are eligible for local ablative therapy (Cohort 3)
Presence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
In patients with suspected leptomeningeal disease, the diagnosis of leptomeningeal disease should be confirmed by the presence of neurological or imaging signs and/or positive cerebrospinal fluid (CSF) cytology.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
No uncontrolled arrhythmia; no myocardial infarction in the last 6 months.
Females should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing Hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for the institution
Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
Females of child-bearing potential should use reliable methods of contraception from the time of screening until 3 months after discontinuing osimertinib. Acceptable methods of contraception include total and true sexual abstinence, tubal ligation, 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 male sexual partner for intercourse.
Male patients should be willing to use barrier contraception. Male patients should be asked to use barrier contraceptives (i.e., by use of condoms) during sex with all of their female partners during the trial and for a washout period of 3 months. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing osimertinib treatment. If male patients wish to father children, they should be advised to arrange for freezing of sperm samples prior to the start of osimertinib treatment.
Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

EXCLUSION CRITERIA

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception, of alop

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Data sourced from ClinicalTrials.gov (NCT02759835). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.