Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery
- Conditions
- Head and Neck Mucosal MelanomaMucosal MelanomaNasopharyngeal Mucosal MelanomaOral Cavity Mucosal MelanomaPenile Mucosal MelanomaRectal MelanomaRecurrent Mucosal MelanomaSinonasal Mucosal MelanomaUrethral MelanomaUrinary System Mucosal Melanoma
- Interventions
- Procedure: Biospecimen CollectionProcedure: Bone ScanProcedure: Computed TomographyProcedure: Echocardiography TestProcedure: Magnetic Resonance ImagingDrug: Placebo AdministrationProcedure: Positron Emission Tomography
- Registration Number
- NCT05111574
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial tests whether nivolumab in combination with cabozantinib works in patients with mucosal melanoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving nivolumab in combination with cabozantinib could prevent cancer from returning.
- Detailed Description
PRIMARY OBJECTIVE:
I. To compare the efficacy of adjuvant nivolumab (480 mg every \[q\]4 weeks) versus nivolumab plus cabozantinib s-malate (cabozantinib) (40 mg daily) in patients with mucosal melanoma.
SECONDARY OBJECTIVES:
I. To compare overall survival between the two adjuvant therapies. II. To evaluate the adverse effects in each arm. III. To assess the correlation between PD-L1 expression in tumor cells with survival (recurrence free survival \[RFS\] and overall survival \[OS\]).
IV. To evaluate the overall response rate (ORR), duration of response (DOR), progression free survival (PFS), and OS of nivolumab plus cabozantinib in patients who cannot undergo gross total resection of disease or have metastatic disease at baseline.
V. Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue.
OUTLINE: Patients whose tumor has been fully removed by surgery are randomized to Arm 1 or Arm 2. Patients whose tumor has not been fully removed by surgery or has spread are assigned to Arm 3.
ARM 1: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and cabozantinib orally (PO) once daily (QD) of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.
ARM 2: Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.
ARM 3: Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo echocardiogram (ECHO) during screening and as clinically indicated throughout the trial. Patients may undergo computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial.
After completion of study treatment, patients are followed up every 3 months until disease progression, and then every 6 months for up to 5 years from registration or until death.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 99
-
STEP 0 INCLUSION CRITERIA
-
Histologically proven mucosal melanoma by local pathology
-
Central PD-L1 tumor tissue submission
-
STEP 1 INCLUSION CRITERIA
-
Receipt of the central PD-L1 testing results available
- Report is required for randomization of resection R0 or R1 patients
- Testing must be started in Step 0 but results can be reported after registration for resection R2 patients
-
Disease status-Resected R0 or R1 disease patients. Patients eligible for randomization have resected R0 or R1 disease (with negative margins or positive microscopic margins) that must meet one of the following 4 criteria as defined below:
-
Regional lymph node (LN) involvement; OR
-
In-transit metastases/satellite primary disease; OR
-
Single localized, primary disease meeting one of the following site-specific requirements:
-
Head/neck - Sinonasal (including nasopharynx): any primary lesion; Nasal or oral cavity; pT4a or above, given slightly improved OS
- NOTE: Conjunctival: does not meet the qualification for eligibility
-
Anorectal - any primary lesion
-
Vaginal/cervical - any primary, as they have 5 year OS rates of 5-25%
-
Urinary tract - any primary urethral or bladder tumor
-
Penile
-
Vulvar- American Joint Committee on Cancer (AJCC) cutaneous stage IIB or higher
-
Esophageal/gallbladder - any primary
-
-
Locoregionally recurrent following prior resection, meeting at least one of the above criteria
-
In addition, patients must have undergone cross-sectional imaging of the brain, chest, abdomen and pelvis with no evidence of distant metastatic disease
-
-
Disease status-Non-resected R2 or metastatic disease patients
- Non-resected R2 or metastatic disease that is assessable and measurable radiographically or by physical examination
-
Prior Treatment:
- No prior systemic checkpoint inhibitor therapy of mucosal melanoma, including in the adjuvant setting, is allowed. Prior adjuvant chemotherapy or interferon is allowed.
- No other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator. Exceptions may allow for adjuvant no evidence of disease (NED) cancers undergoing hormone based therapy may be eligible pending the other eligibility criteria are met and the principal investigator (PI) affirms the hormonal agent would not change the melanoma response.
- Any radiation must have completed 28 days prior to randomization and the patient must have adequately recovered from its effects.
- For resectable patients only: Surgery must have completed 28 days prior to randomization.
- For resectable patients only: Surgery must have completed no more than 84 days prior to randomization.
-
Not pregnant and not nursing, because this study has an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
-
Age >= 18 years
-
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
-
Absolute neutrophil count (ANC) >= 1,500/mm^3
-
Platelet count >= 100,000/mm^3
-
Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 50mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
-
Albumin >= 2.8 g/dL
-
Total bilirubin =< 1.5 x upper limit of normal (ULN)
-
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
-
No cardiovascular disease, including:
- No history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary artery bypass graft (CABG) coronary angioplasty, or stenting within 6 months prior to study entry.
- No history of current class II or higher congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- No refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg despite adequate attempts at anti-hypertensive therapy.
- No history of myocarditis.
- No history of syncope of cardiovascular etiology, uncontrolled cardiac arrhythmia, history of Mobitz II second degree or third degree heart block without a permanent pacemaker in Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (TIA) within the past 3 months.
- No corrected QT interval by Fridericia's formula (QTcF) > 500 msec. Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard.
-
No underlying hematologic issues, including:
- Congenital bleeding diathesis
- Gastrointestinal (GI) bleeding requiring intervention within the past 6 months, unless directly related to mucosal melanoma
- Active hemoptysis within 42 days prior to study enrollment.
- Active tumor lesions with cavitations or tumor lesions which invade, encase, or abut major blood vessels. The anatomic location and characteristics of primary tumors or metastases as well as the medical history should be carefully reviewed in the selection of subjects for treatment with cabozantinib/placebo.
- Pulmonary emboli or deep vein thromboses (DVT) that require an active anticoagulation regimen.
- No known or suspected history of cytopenia (low white blood cell [WBC], hemoglobin or platelet count) of greater than 3 months duration with an unknown cause, myelodysplastic syndrome, or hematologic malignancies.
-
No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or viral infection requiring treatment at the time of pre-registration (e.g., active symptoms of COVID-19 infection or a post-infectious symptomatic autoimmune syndrome, serious bacterial infections requiring antibiotics).
-
No known or suspected gastrointestinal disorder affecting absorption of oral medications.
-
Comorbid conditions:
-
No active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (> 10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
-
No history of autoimmune motor neuropathy (e.g., Guillain-Barre syndrome, myasthenia gravis) or non-infectious pneumonitis.
-
No history of severe allergic reactions to an unknown allergen or any components of the study drugs or its excipients.
-
No history of gastrointestinal perforation or abdominal fistula.
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No clinically suspected central nervous system (CNS) (leptomeningeal or parenchymal) metastases. Patients with a history of CNS metastasis(s) will be allowed as long as
- The metastatic site(s) were adequately treated as demonstrated by clinical and radiographic improvement, AND
- The patient has recovered from the intervention (no residual adverse events > Common Terminology Criteria for Adverse Events [CTCAE] grade 1), AND
- The patient has remained without occurrence of new or worsening CNS symptoms for a period of 28 days prior to enrollment.
-
No history of seizure or any condition that may increase the patient's seizure risk (e.g., prior cortical stroke, significant brain trauma) within 2 years.
-
No clinically active or chronic liver disease resulting in moderate/severe hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding due to liver dysfunction.
-
No untreated spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression. Spinal metastases must have completed planned radiation or surgical therapy prior to registration.
-
-
Concomitant medications:
- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 5 days prior to the start of study treatment.
- Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 5 days prior to the start of study treatment.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 (nivolumab, placebo) Biospecimen Collection Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 2 (nivolumab, placebo) Bone Scan Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 2 (nivolumab, placebo) Computed Tomography Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 2 (nivolumab, placebo) Echocardiography Test Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 1 (nivolumab, cabozantinib) Biospecimen Collection Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 1 (nivolumab, cabozantinib) Bone Scan Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 1 (nivolumab, cabozantinib) Cabozantinib S-malate Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 1 (nivolumab, cabozantinib) Computed Tomography Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 1 (nivolumab, cabozantinib) Echocardiography Test Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 2 (nivolumab, placebo) Nivolumab Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 1 (nivolumab, cabozantinib) Magnetic Resonance Imaging Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 3 (nivolumab, cabozantinib) Biospecimen Collection Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 1 (nivolumab, cabozantinib) Nivolumab Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 1 (nivolumab, cabozantinib) Positron Emission Tomography Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 2 (nivolumab, placebo) Magnetic Resonance Imaging Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 2 (nivolumab, placebo) Placebo Administration Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 2 (nivolumab, placebo) Positron Emission Tomography Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 3 (nivolumab, cabozantinib) Bone Scan Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 3 (nivolumab, cabozantinib) Cabozantinib S-malate Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 3 (nivolumab, cabozantinib) Computed Tomography Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 3 (nivolumab, cabozantinib) Echocardiography Test Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 3 (nivolumab, cabozantinib) Magnetic Resonance Imaging Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 3 (nivolumab, cabozantinib) Nivolumab Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial. Arm 3 (nivolumab, cabozantinib) Positron Emission Tomography Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo bone scans, as well as optional blood and tissue sample collection throughout the trial.
- Primary Outcome Measures
Name Time Method Recurrence free survival (RFS) Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years Will evaluate RFS of single agent adjuvant nivolumab plus placebo compared to the combination treatment of adjuvant nivolumab plus cabozantinib in patients with resected mucosal melanoma.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) Number of days from registration until death (due to any cause, assessed up to 5 years Will be evaluated utilizing the Kaplan-Meier (KM) method and, when appropriate, cox proportional hazards models. Median OS is calculated (along with 95% Confidence intervals) using the KM method. A Cox proportional hazards model is built to compare arms 1 and 2 with respect to OS.
RFS Number of days from registration until either local or distant recurrence or death (due to any cause), assessed up to 5 years Median RFS will be calculated (along with 95% Confidence intervals) using the KM method. A Cox proportional hazards model will also be built to compare arms 1 and 2 with respect to RFS, with and without stratifying for PD-L1 categorization. For non-resected cohort, If a patient in this group has surgery, their RFS data will be censored at the time of surgery.
Progression free survival Number of days from registration until either radiographic or clinical progression or death (due to any cause), assessed up to 5 years Will be evaluated in multiple settings utilizing the KM method and, when appropriate, cox proportional hazards models.
Objective response rate (Arm 3) Up to 5 years Will assess this endpoint utilizing a two-stage Simon that looks to improve from a rate of 20% to 47%.
Duration of response (Arm 3) Time from the first evidence of response until progression, assessed up to 5 years A KM analysis is performed to calculate the median duration of response and 95% confidence intervals are constructed.
Incidence of adverse events Up to 5 years The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5.0. The frequency and percentage of grade 3+ adverse events will be summarized.
Trial Locations
- Locations (142)
Sutter Auburn Faith Hospital
🇺🇸Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
Palo Alto Medical Foundation-Fremont
🇺🇸Fremont, California, United States
Keck Medicine of USC Koreatown
🇺🇸Los Angeles, California, United States
Los Angeles General Medical Center
🇺🇸Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Memorial Medical Center
🇺🇸Modesto, California, United States
USC Norris Oncology/Hematology-Newport Beach
🇺🇸Newport Beach, California, United States
Palo Alto Medical Foundation Health Care
🇺🇸Palo Alto, California, United States
Stanford Cancer Institute Palo Alto
🇺🇸Palo Alto, California, United States
Sutter Roseville Medical Center
🇺🇸Roseville, California, United States
Sutter Medical Center Sacramento
🇺🇸Sacramento, California, United States
California Pacific Medical Center-Pacific Campus
🇺🇸San Francisco, California, United States
UCSF Medical Center-Mission Bay
🇺🇸San Francisco, California, United States
Palo Alto Medical Foundation-Santa Cruz
🇺🇸Santa Cruz, California, United States
Sutter Pacific Medical Foundation
🇺🇸Santa Rosa, California, United States
Palo Alto Medical Foundation-Sunnyvale
🇺🇸Sunnyvale, California, United States
Sutter Solano Medical Center/Cancer Center
🇺🇸Vallejo, California, United States
The Melanoma and Skin Cancer Institute
🇺🇸Englewood, Colorado, United States
UM Sylvester Comprehensive Cancer Center at Aventura
🇺🇸Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
🇺🇸Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸Deerfield Beach, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
🇺🇸Plantation, Florida, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Saint Alphonsus Cancer Care Center-Caldwell
🇺🇸Caldwell, Idaho, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
Kootenai Health - Coeur d'Alene
🇺🇸Coeur d'Alene, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
🇺🇸Nampa, Idaho, United States
Kootenai Clinic Cancer Services - Post Falls
🇺🇸Post Falls, Idaho, United States
Kootenai Clinic Cancer Services - Sandpoint
🇺🇸Sandpoint, Idaho, United States
Rush - Copley Medical Center
🇺🇸Aurora, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Northwestern Medicine Cancer Center Kishwaukee
🇺🇸DeKalb, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
Northwestern Medicine Glenview Outpatient Center
🇺🇸Glenview, Illinois, United States
Northwestern Medicine Grayslake Outpatient Center
🇺🇸Grayslake, Illinois, United States
Northwestern Medicine Lake Forest Hospital
🇺🇸Lake Forest, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
Northwestern Medicine Orland Park
🇺🇸Orland Park, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Springfield Memorial Hospital
🇺🇸Springfield, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Rush-Copley Healthcare Center
🇺🇸Yorkville, Illinois, United States
Mary Greeley Medical Center
🇺🇸Ames, Iowa, United States
McFarland Clinic - Ames
🇺🇸Ames, Iowa, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
🇺🇸Ankeny, Iowa, United States
McFarland Clinic - Boone
🇺🇸Boone, Iowa, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
🇺🇸Clive, Iowa, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
🇺🇸Des Moines, Iowa, United States
McFarland Clinic - Trinity Cancer Center
🇺🇸Fort Dodge, Iowa, United States
McFarland Clinic - Jefferson
🇺🇸Jefferson, Iowa, United States
McFarland Clinic - Marshalltown
🇺🇸Marshalltown, Iowa, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
🇺🇸Waukee, Iowa, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
Trinity Health Grand Rapids Hospital
🇺🇸Grand Rapids, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Ascension Borgess Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Trinity Health Muskegon Hospital
🇺🇸Muskegon, Michigan, United States
Corewell Health Lakeland Hospitals - Niles Hospital
🇺🇸Niles, Michigan, United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
🇺🇸Norton Shores, Michigan, United States
Corewell Health Reed City Hospital
🇺🇸Reed City, Michigan, United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
University of Michigan Health - West
🇺🇸Wyoming, Michigan, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Parkland Health Center - Farmington
🇺🇸Farmington, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
BJC Outpatient Center at Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Community Hospital of Anaconda
🇺🇸Anaconda, Montana, United States
Billings Clinic Cancer Center
🇺🇸Billings, Montana, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Benefis Sletten Cancer Institute
🇺🇸Great Falls, Montana, United States
Logan Health Medical Center
🇺🇸Kalispell, Montana, United States
Community Medical Center
🇺🇸Missoula, Montana, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
Northwell Health/Center for Advanced Medicine
🇺🇸Lake Success, New York, United States
NYU Langone Hospital - Long Island
🇺🇸Mineola, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Miami Valley Hospital South
🇺🇸Centerville, Ohio, United States
Good Samaritan Hospital - Cincinnati
🇺🇸Cincinnati, Ohio, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Premier Blood and Cancer Center
🇺🇸Dayton, Ohio, United States
Dayton Physician LLC - Englewood
🇺🇸Dayton, Ohio, United States
Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Miami Valley Cancer Care and Infusion
🇺🇸Greenville, Ohio, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
Cancer Centers of Southwest Oklahoma Research
🇺🇸Lawton, Oklahoma, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Saint Alphonsus Cancer Care Center-Ontario
🇺🇸Ontario, Oregon, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Cancer Institute (UPCI)
🇺🇸Pittsburgh, Pennsylvania, United States
Asplundh Cancer Pavilion
🇺🇸Willow Grove, Pennsylvania, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
VCU Massey Cancer Center at Stony Point
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University/Massey Cancer Center
🇺🇸Richmond, Virginia, United States
HSHS Sacred Heart Hospital
🇺🇸Eau Claire, Wisconsin, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Saint Vincent Hospital Cancer Center Green Bay
🇺🇸Green Bay, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
🇺🇸Green Bay, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
🇺🇸Madison, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
🇺🇸Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Marshfield Medical Center - Minocqua
🇺🇸Minocqua, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Oconto Falls
🇺🇸Oconto Falls, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Sheboygan
🇺🇸Sheboygan, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Saint Vincent Hospital Cancer Center at Sturgeon Bay
🇺🇸Sturgeon Bay, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
Ottawa Hospital and Cancer Center-General Campus
🇨🇦Ottawa, Ontario, Canada
Odette Cancer Centre- Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
University Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada