RECRUITING

Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy

Conditions

Carcinoma, Non-Small-Cell Lung Advanced Non Small Cell Lung Cancer (NSCLC)Metastatic NSCLC circulating tumor DNA (ctDNA)G360

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This clinical trial plans to assess to what extent the on-treatment circulating tumor DNA (ctDNA) can predict the subset of patients with NSCLC who will respond to immunotherapy treatment only and which patients will need both immunotherapy and chemotherapy modalities for their treatment regimen.

Official Title

A Multicenter Phase II Randomized Trial Of Immunotherapy Versus Chemotherapy Guided By Circulating Tumor DNA-Based Molecular Response On Patients With Metastatic NSCLC

Quick Facts

Study Start:2023-09-29

Study Completion:2026-04-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05715229

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Eligible patients will have newly diagnosed, previously untreated histologically documented Stage IV NSCLC 2. Eligible patients will be required to have positive PD-L1 expression ≥1% by IHC using Dako 22C3 assay. 3. Patients will require a baseline Guardant360 CDx test prior to enrollment 4. Patients willing to undergo serial ctDNA testing as required by protocol 5. Patients will be over the age of 18 6. Life expectancy ≥12 weeks 7. Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable disease determined per the treating investigator. 8. Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization 9. ECOG Performance Score ≤2 10. Adequate organ function 11. Hemoglobin \> 9 g/dL 12. Platelets \> 100,000mm3 or 100 x 109/L 13. AST, ALT \< 2.5 x ULN with no liver metastases or \< 5x ULN with the presence of liver metastases 14. Total bilirubin \< 1.5 x ULN if no liver metastases or \< 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases 15. Absolute neutrophil count (ANC) \> 1500 cells/mm3 16. Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault's equation 17. Willing to use highly effective contraceptive measures if child-bearing potential or if the patient's sexual partner is a woman of childbearing potential: a. Female subjects should be using a highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to starting 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: i. Post-menopausal is defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not a tubal ligation b. Male subjects should be willing to use barrier contraception	1. Patients under the age of 18 2. Inability to provide informed consent by either the patient or the authorized representative 3. Patients with known EGFR, ALK, ROS1, MET, and RET oncogenic driver alterations that have approved first-line targeted therapies are excluded from the study (All patients must have a tissue or blood-based testing to identify these driver alterations) 4. Patients with no detectable ctDNA or ctDNA VAF ≤ 0.3% on Guardant360 CDx at baseline 5. Subjects with untreated CNS metastases are excluded. 6. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization. 7. Subjects with carcinomatous meningitis 8. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization 9. Subjects with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to randomization and no additional therapy is required or anticipated to be needed during the study period. 10. Other active malignancy requiring concurrent intervention. 11. Subjects with an active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, and hypothyroidism only require hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 12. Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroids \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. 13. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity. 14. Significant uncontrolled cardiovascular disease, including but not limited to, any of the following: 1. Uncontrolled hypertension, which is defined as systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 100 mm Hg despite optimal medical management. 2. Active coronary artery disease, including unstable all newly diagnosed angina within 3 months of study enrollment. 3. Myocardial infarction in the past 6 months. 4. History of congenital long QT syndrome. 5. History of clinically significant arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes. 6. Uncontrolled heart failure, defined as class III of 4 by the New York Heart Association functional classification. 7. History of a current diagnosis of myocarditis. 15. the Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results. 16. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection 17. Subjects with Grade 2 peripheral neuropathy 18. Life expectancy \<12 weeks

Inclusion Criteria

Exclusion Criteria

1. Eligible patients will have newly diagnosed, previously untreated histologically documented Stage IV NSCLC
2. Eligible patients will be required to have positive PD-L1 expression ≥1% by IHC using Dako 22C3 assay.
3. Patients will require a baseline Guardant360 CDx test prior to enrollment
4. Patients willing to undergo serial ctDNA testing as required by protocol
5. Patients will be over the age of 18
6. Life expectancy ≥12 weeks
7. Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable disease determined per the treating investigator.
8. Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization
9. ECOG Performance Score ≤2
10. Adequate organ function
11. Hemoglobin \> 9 g/dL
12. Platelets \> 100,000mm3 or 100 x 109/L
13. AST, ALT \< 2.5 x ULN with no liver metastases or \< 5x ULN with the presence of liver metastases
14. Total bilirubin \< 1.5 x ULN if no liver metastases or \< 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
15. Absolute neutrophil count (ANC) \> 1500 cells/mm3
16. Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault's equation
17. Willing to use highly effective contraceptive measures if child-bearing potential or if the patient's sexual partner is a woman of childbearing potential: a. Female subjects should be using a highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to starting 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: i. Post-menopausal is defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments ii. Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the the post-menopausal range for the institution iii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not a tubal ligation b. Male subjects should be willing to use barrier contraception

1. Patients under the age of 18
2. Inability to provide informed consent by either the patient or the authorized representative
3. Patients with known EGFR, ALK, ROS1, MET, and RET oncogenic driver alterations that have approved first-line targeted therapies are excluded from the study (All patients must have a tissue or blood-based testing to identify these driver alterations)
4. Patients with no detectable ctDNA or ctDNA VAF ≤ 0.3% on Guardant360 CDx at baseline
5. Subjects with untreated CNS metastases are excluded.
6. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization.
7. Subjects with carcinomatous meningitis
8. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization
9. Subjects with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to randomization and no additional therapy is required or anticipated to be needed during the study period.
10. Other active malignancy requiring concurrent intervention.
11. Subjects with an active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, and hypothyroidism only require hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
12. Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroids \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
13. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
14. Significant uncontrolled cardiovascular disease, including but not limited to, any of the following:
1. Uncontrolled hypertension, which is defined as systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 100 mm Hg despite optimal medical management.
2. Active coronary artery disease, including unstable all newly diagnosed angina within 3 months of study enrollment.
3. Myocardial infarction in the past 6 months.
4. History of congenital long QT syndrome.
5. History of clinically significant arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes.
6. Uncontrolled heart failure, defined as class III of 4 by the New York Heart Association functional classification.
7. History of a current diagnosis of myocarditis.
15. the Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
16. Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
17. Subjects with Grade 2 peripheral neuropathy
18. Life expectancy \<12 weeks

Contacts and Locations

Study Contact

Lauren Finaldi

CONTACT

551-996-5228

Lauren.Finaldi@hmhn.org

Suzanne Kosky

CONTACT

551-996-3986

Suzanne.Kosky@hmhn.org

Principal Investigator

Martin Gutierrez, MD

PRINCIPAL_INVESTIGATOR

Hackensack Meridian Health

Study Locations (Sites)

Lombardi Comprehensive Cancer Center, Georgetown University

Washington, District of Columbia, 20007

United States

John Theurer Cancer Center, Hackensack Meridian Health

Hackensack, New Jersey, 07410

United States

Jersey Shore University Medical Center

Neptune, New Jersey, 07753

United States

Collaborators and Investigators

Sponsor: Hackensack Meridian Health

Martin Gutierrez, MD, PRINCIPAL_INVESTIGATOR, Hackensack Meridian Health

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-29

Study Completion Date2026-04-28

Study Record Updates

Study Start Date2023-09-29

Study Completion Date2026-04-28

Terms related to this study

Keywords Provided by Researchers

Advanced Non Small Cell Lung Cancer (NSCLC)
Metastatic NSCLC
circulating tumor DNA (ctDNA)
G360

Additional Relevant MeSH Terms

Carcinoma, Non-Small-Cell Lung