A Study Evaluating Whether Pembrolizumab Alone or in Combination With CMP-001 Improves Efficacy in Patients With Operable Melanoma
Clinical Stage III Cutaneous Melanoma AJCC v8, Melanoma of Unknown Primary, Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
About this trial
This is an interventional treatment trial for Clinical Stage III Cutaneous Melanoma AJCC v8
Eligibility Criteria
Inclusion Criteria:
- Patient must be >= 18 years of age
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Patient must have a histologic diagnosis of melanoma belonging to the following American Joint Committee on Cancer (AJCC) 8th edition TNM stages:
- T0, Tx or T1-4; and
- N1b, N2b, N2c, N3b or N3c
Patients may have a presentation with primary melanoma with concurrent regional nodal and/or in-transit metastasis; or patients may have a history of primary melanoma or unknown primary melanoma presenting with clinically detected regional nodal and/or in-transit recurrence; and may belong to any of the following groups:
- Primary cutaneous melanoma with clinically apparent regional lymph node metastases and/or in-transit metastases
- Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin
- Primary cutaneous melanoma with concurrent nodal disease involving a single (or multiple) regional nodal group(s) if considered potentially surgically resectable at baseline
- Clinically detected nodal melanoma (if single site) arising from an unknown primary
In-transit cutaneous metastases with or without regional lymph node involvement permitted if considered potentially surgically resectable at baseline
- NOTE: Patients with mucosal and/or uveal melanoma are not eligible for the study
- Patient must be a candidate for definitive surgery and have met with the treating surgical oncologist prior to randomization
Patient must have the presence of injectable and measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, documented by scans obtained within 4 weeks prior to randomization
- NOTE: Injectable disease is defined as an accessible lesion in the skin, subcutaneous tissue or lymph nodes (LN) close to the skin and palpable by physical examination or approachable with ultrasound guidance
- Absolute neutrophil count (ANC) >= 1,500 /mcL (obtained within 4 weeks prior to randomization)
- Hemoglobin (Hgb) >= 9 g/dL or >= 5.6 mmol/L (obtained within 4 weeks prior to randomization)
- Platelets >= 100,000 / mcL (obtained within 4 weeks prior to randomization)
- Serum creatinine =< 1.5 x institutional upper limit of normal (ULN) or measured or calculated creatinine clearance > 60 mL/min (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl] for patients with creatinine levels > 1.5 x institutional ULN) (obtained within 4 weeks prior to randomization)
- Serum total bilirubin =< 1.5 x institutional ULN; for total bilirubin levels > 1.5 x ULN, but =< 3 x ULN, the direct bilirubin must be =< the institutional ULN (obtained within 4 weeks prior to randomization)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 4 weeks prior to randomization)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x institutional ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (obtained within 4 weeks prior to randomization)
- Activated partial thromboplastin time (aPTT) =< 1.5 x institutional ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (obtained within 4 weeks prior to randomization)
- Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to randomization are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
Exclusion Criteria:
- Patient must not have received any live vaccine within 30 days prior to randomization and while participating in the study. Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and COVID-19 (Note: intranasal influenza vaccines, such as Flu-Mist are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events)
- Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab if the test done for eligibility/randomization is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or abstaining from sexual intercourse from time of randomization, while on study treatment, and continue for 26 weeks after the last dose of protocol treatment
- Patient must not have received prior systemic therapy for melanoma including systemic therapy with an anti-PD-1, anti-PD-L1, anti-CTLA-4, BRAF/MEK inhibitor combination and/or TLR-9 agonist
Patient must not have a diagnosis of immunodeficiency or be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization, except as noted here
- Patients who are currently receiving steroids at a dose of prednisone =< 5 mg daily (or equivalent) are permitted to enroll
- Patients who require topical, ophthalmologic and inhalational steroids are permitted to enroll
- Patients with hypothyroidism who are stable on hormone replacement are permitted to enroll
- Patients who require active immunosuppression with corticosteroids at a dose of prednisone > 5 mg daily (or equivalent) for any reason are ineligible
- Patients with adrenal insufficiency are ineligible
- Patients who have developed autoimmune disorders of grade 4 while on prior immunotherapy are not permitted to enroll on this study. Patients who developed autoimmune disorders of grade =< 3 may enroll if the disorder has resolved to grade =< 1 and the patient has been off systemic corticosteroids at doses > 5 mg for at least 2 weeks prior to randomization
- Patients with a history of brain metastases are not eligible for this study as they do not meet the eligibility staging criteria
- Patient must not have had an allogeneic tissue/solid organ transplant
- Patient must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Patient must not have severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
- Patient must not have an active infection requiring systemic therapy
- Patient must not have a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the study
Sites / Locations
- Anchorage Associates in Radiation Medicine
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Fairbanks Memorial HospitalRecruiting
- Mercy Hospital Fort Smith
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Epic Care-DublinRecruiting
- Bay Area Breast Surgeons Inc
- Epic Care Partners in Cancer CareRecruiting
- Contra Costa Regional Medical CenterRecruiting
- Alta Bates Summit Medical Center - Summit Campus
- Bay Area Tumor Institute
- Saint Joseph Hospital - OrangeRecruiting
- UC Irvine Health/Chao Family Comprehensive Cancer CenterRecruiting
- Epic Care Cyberknife CenterRecruiting
- Rocky Mountain Cancer Centers-AuroraRecruiting
- The Medical Center of Aurora
- Rocky Mountain Cancer Centers-BoulderRecruiting
- Rocky Mountain Cancer Centers - CentennialRecruiting
- Presbyterian - Saint Lukes Medical Center - Health One
- Rocky Mountain Cancer Centers-MidtownRecruiting
- Rocky Mountain Cancer Centers-RoseRecruiting
- Mountain Blue Cancer Care Center - Swedish
- Rocky Mountain Cancer Centers - SwedishRecruiting
- Swedish Medical Center
- The Melanoma and Skin Cancer Institute
- North Colorado Medical Center
- Rocky Mountain Cancer Centers-LittletonRecruiting
- Rocky Mountain Cancer Centers-Sky RidgeRecruiting
- Sky Ridge Medical Center
- McKee Medical Center
- Rocky Mountain Cancer Centers-Thornton
- UM Sylvester Comprehensive Cancer Center at AventuraRecruiting
- UM Sylvester Comprehensive Cancer Center at Coral GablesRecruiting
- UM Sylvester Comprehensive Cancer Center at Deerfield BeachRecruiting
- University of Miami Miller School of Medicine-Sylvester Cancer CenterRecruiting
- UM Sylvester Comprehensive Cancer Center at PlantationRecruiting
- Saint Luke's Cancer Institute - Boise
- Saint Luke's Cancer Institute - Fruitland
- Saint Luke's Cancer Institute - Meridian
- Saint Luke's Cancer Institute - Nampa
- Saint Luke's Cancer Institute - Twin Falls
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- SIH Cancer Institute
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- University of IllinoisRecruiting
- Cancer Care Specialists of Illinois - DecaturRecruiting
- Decatur Memorial Hospital
- Illinois CancerCare-Dixon
- Crossroads Cancer CenterRecruiting
- Illinois CancerCare-Eureka
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Illinois CancerCare-Kewanee Clinic
- Illinois CancerCare-Macomb
- Good Samaritan Regional Health Center
- Cancer Care Center of O'FallonRecruiting
- Illinois CancerCare-Ottawa Clinic
- Illinois CancerCare-Pekin
- Illinois CancerCare-Peoria
- Methodist Medical Center of Illinois
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- Southern Illinois University School of MedicineRecruiting
- Springfield ClinicRecruiting
- Memorial Medical Center
- Illinois CancerCare - Washington
- Reid HealthRecruiting
- Mary Greeley Medical CenterRecruiting
- McFarland Clinic - AmesRecruiting
- McFarland Clinic - BooneRecruiting
- McFarland Clinic - Trinity Cancer CenterRecruiting
- McFarland Clinic - JeffersonRecruiting
- McFarland Clinic - MarshalltownRecruiting
- Central Care Cancer Center - Garden City
- Central Care Cancer Center - Great Bend
- Louisiana Hematology Oncology Associates LLCRecruiting
- Mary Bird Perkins Cancer CenterRecruiting
- Terrebonne General Medical CenterRecruiting
- Bronson Battle CreekRecruiting
- Helen DeVos Children's Hospital at Spectrum Health
- Spectrum Health at Butterworth CampusRecruiting
- Trinity Health Grand Rapids HospitalRecruiting
- Bronson Methodist HospitalRecruiting
- West Michigan Cancer CenterRecruiting
- Ascension Borgess Cancer CenterRecruiting
- Borgess Medical Center
- Trinity Health Muskegon HospitalRecruiting
- Lakeland Hospital Niles
- Cancer and Hematology Centers of Western Michigan - Norton ShoresRecruiting
- Spectrum Health Reed City HospitalRecruiting
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer CenterRecruiting
- Munson Medical CenterRecruiting
- University of Michigan Health - WestRecruiting
- Saint Louis Cancer and Breast Institute-Ballwin
- Central Care Cancer Center - Bolivar
- Saint Francis Medical Center
- Southeast Cancer Center
- Parkland Health Center - FarmingtonRecruiting
- Capital Region Southwest Campus
- Freeman Health System
- Mercy Hospital Joplin
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Mercy Hospital South
- Missouri Baptist Medical CenterRecruiting
- Mercy Hospital Saint Louis
- Sainte Genevieve County Memorial HospitalRecruiting
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Missouri Baptist Sullivan HospitalRecruiting
- Missouri Baptist Outpatient Center-Sunset HillsRecruiting
- Saint Patrick Hospital - Community HospitalRecruiting
- Indu and Raj Soin Medical Center
- Dayton Physicians LLC-Miami Valley SouthRecruiting
- Miami Valley Hospital South
- Oncology Hematology Care Inc-Kenwood
- Miami Valley Hospital
- Dayton Physician LLC-Miami Valley Hospital NorthRecruiting
- Miami Valley Hospital North
- Armes Family Cancer CenterRecruiting
- Blanchard Valley Hospital
- Orion Cancer Care
- Atrium Medical Center-Middletown Regional Hospital
- Dayton Physicians LLC-AtriumRecruiting
- Dayton Physicians LLC-WayneRecruiting
- Wayne HospitalRecruiting
- Greater Dayton Cancer CenterRecruiting
- Kettering Medical CenterRecruiting
- Springfield Regional Cancer Center
- Springfield Regional Medical Center
- Dayton Physicians LLC - Troy
- Upper Valley Medical Center
- Mercy Hospital Oklahoma City
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas Clinic
- Bay Area Hospital
- Providence Newberg Medical CenterRecruiting
- Providence Portland Medical CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Saint Luke's Cancer Center - AllentownRecruiting
- Saint Luke's University Hospital-Bethlehem CampusRecruiting
- Saint Luke's Hospital-Anderson CampusRecruiting
- University of Pittsburgh Cancer Institute (UPCI)Recruiting
- Saint Luke's Hospital-Quakertown CampusRecruiting
- Guthrie Medical Group PC-Robert Packer HospitalRecruiting
- Avera Cancer Institute-AberdeenRecruiting
- Avera Cancer InstituteRecruiting
- Huntsman Cancer Institute/University of UtahRecruiting
- Central Vermont Medical Center/National Life Cancer TreatmentRecruiting
- University of Vermont Medical CenterRecruiting
- University of Virginia Cancer CenterRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- Providence Regional Cancer System-Aberdeen
- PeaceHealth Saint Joseph Medical Center
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Providence Regional Cancer Partnership
- Swedish Cancer Institute-Issaquah
- Kadlec Clinic Hematology and OncologyRecruiting
- Providence Regional Cancer System-Lacey
- PeaceHealth Saint John Medical CenterRecruiting
- Jefferson HealthcareRecruiting
- Swedish Medical Center-Ballard Campus
- Swedish Medical Center-First Hill
- PeaceHealth United General Medical Center
- PeaceHealth Southwest Medical Center
- Providence Saint Mary Regional Cancer Center
- Marshfield Medical Center-EC Cancer CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Medical College of WisconsinRecruiting
- Marshfield Clinic-Minocqua CenterRecruiting
- Marshfield Medical Center-Rice LakeRecruiting
- Marshfield Medical Center-River Region at Stevens PointRecruiting
- Marshfield Medical Center - WestonRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Arm A (pembrolizumab)
Arm B (CMP-001, pembrolizumab)
NEOADJUVANT PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET/CT throughout the trial and may undergo optional biopsy at baseline and disease progression and optional collection of blood samples throughout the trial.
NEOADJUVANT PHASE: Patients receive CMP-001 SC on day 1 of cycle 1 and then intratumorally on days 8 and 15 of cycle 1, days 1, 8, and 15 of cycle 2, and day 1 of cycle 3. Patients also receive pembrolizumab IV over 30 minutes on day 8 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET/CT throughout the trial and may undergo optional biopsy at baseline and disease progression and optional collection of blood samples throughout the trial.