Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy (G360-IIT)
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|ClinicalTrials.gov Identifier: NCT05715229|
Recruitment Status : Not yet recruiting
First Posted : February 6, 2023
Last Update Posted : March 6, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Non-Small-Cell Lung||Drug: Nivolumab Drug: Ipilimumab Drug: Carboplatin Drug: Paclitaxel Drug: Pemetrexed||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||108 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Subjects will be randomized 2:1 and patients in both arms will begin treatment with nivolumab 360 mg intravenously every 3 weeks and ipilimumab 1 mg/kg intravenously every 6 weeks. At five weeks of treatment, subjects will have ctDNA response evaluation with Guardant360 Response assay. At the next cycle of treatment (+/- 2 days), patients in the arm A will receive treatment based on the Guardant360 Response assay results, as described below. Arm B will continue the immunotherapy only.|
|Masking:||None (Open Label)|
|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|
|Estimated Study Start Date :||April 15, 2023|
|Estimated Primary Completion Date :||October 30, 2025|
|Estimated Study Completion Date :||October 30, 2025|
Active Comparator: Arm A
Arm A - Intervention arm (Immunotherapy and Chemotherapy)
Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks
Platinum- doublet Chemotherapy (Histology-based) 4 cycles depending on the investigator's discretion.
Carboplatin dosed at AUC 5, and either Paclitaxel 175 mg/m2 for squamous or Pemetrexed 500 mg/m2 for non-squamous
Other Name: Opdivo
Other Name: Yervoy
Other Name: Paraplatin
Arm B - control arm (Immunotherapy only)
Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks
Other Name: Opdivo
Other Name: Yervoy
- Progression Free Survival (PFS) [ Time Frame: Time from randomization to objective disease progression, or death from any cause, whichever first, up to 36 months ]To compare progression free survival in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results.
- Progression Free Survival on Subsequent line of therapy (PFS2) [ Time Frame: Duration of time from randomization to second objective disease progression, or death from any cause, whichever first, up to 36 months ]To compare progression free survival on subsequent line of therapy (PFS2) between patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results
- Overall Survival [ Time Frame: Duration of time from first treatment to time of death, up to 36 months ]To compare overall survival (OS) in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results
- Objective Response Rate [ Time Frame: Duration of time between the date of first treatment and the date of objectively documented progression per irRECIST or the date of initiation of palliative local therapy or the date of subsequent anti-cancer therapy, whichever occurs first, up to 36 mo ]To compare objective response rate (ORR) in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on treatment-ctDNA results.
- Duration of Response [ Time Frame: Duration of time between the date of first confirmed response to the date of the first documented tumor progression (per irRECIST), or death due to any cause, whichever occurs first, up to 36 months ]To compare duration of response (DOR) in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results.
- Safety and Tolerability [ Time Frame: All analyses will be conducted using the 30-day safety window ]Serious adverse events will be summarized by treatment group as number and percentages. Overall summary of SAEs by grade (any grade, grade 3-4, grade 5) will be reported. Overall summary of drug-related SAEs by worst CTC grade (any grade, grade 3-4, grade 5) will be reported.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Eligible patients will have newly diagnosed, previously untreated histologically documented Stage IV NSCLC
- Eligible patients will be required to have positive PD-L1 expression ≥1% by IHC using Dako 22C3 assay.
- Patients will require a baseline Guardant360 CDx test prior to enrollment
- Patients willing to undergo serial ctDNA testing as required by protocol
- Patients will be over the age of 18
- Life expectancy ≥12 weeks
- Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable disease determined per the treating investigator.
- Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization
- ECOG Performance Score ≤2
- Adequate organ function
- Hemoglobin > 9 g/dL
- Platelets > 100,000mm3 or 100 x 109/L
- AST, ALT < 2.5 x ULN with no liver metastases or < 5x ULN with the presence of liver metastases
- 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
- Absolute neutrophil count (ANC) > 1500 cells/mm3
- Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance ≥ 60ml/min calculated by Cockcroft and Gault's equation
- 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
- Patients under the age of 18
- Inability to provide informed consent by either the patient or the authorized representative
- 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)
- Patients with no detectable ctDNA or ctDNA VAF ≤ 0.3% on Guardant360 CDx at baseline
- Subjects with untreated CNS metastases are excluded.
- 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.
- Subjects with carcinomatous meningitis
- Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization
- 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.
- Other active malignancy requiring concurrent intervention.
- 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.
- 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.
- Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
Significant uncontrolled cardiovascular disease, including but not limited to, any of the following:
- Uncontrolled hypertension, which is defined as systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg despite optimal medical management.
- Active coronary artery disease, including unstable all newly diagnosed angina within 3 months of study enrollment.
- Myocardial infarction in the past 6 months.
- History of congenital long QT syndrome.
- History of clinically significant arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or torsade de pointes.
- Uncontrolled heart failure, defined as class III of 4 by the New York Heart Association functional classification.
- History of a current diagnosis of myocarditis.
- 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.
- Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
- Subjects with Grade 2 peripheral neuropathy
- Life expectancy <12 weeks
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05715229
|Contact: Lauren Wiest, RN||551-996-8258||Lauren.Wiest@hmhn.org|
|Contact: Danielle Blair, RNfirstname.lastname@example.org|
|United States, District of Columbia|
|Lombardi Comprehensive Cancer Center, Georgetown University|
|Washington, District of Columbia, United States, 20007|
|United States, New Jersey|
|John Theurer Cancer Center, Hackensack Meridian Health|
|Hackensack, New Jersey, United States, 07410|
|Jersey Shore Medical Center|
|Neptune, New Jersey, United States, 07753|
|Principal Investigator:||Martin Gutierrez, MD||Hackensack Meridian Health|
|Responsible Party:||Hackensack Meridian Health|
|Other Study ID Numbers:||
|First Posted:||February 6, 2023 Key Record Dates|
|Last Update Posted:||March 6, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||Yes|
Advanced Non Small Cell Lung Cancer (NSCLC)
circulating tumor DNA (ctDNA)
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors