Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma

Overview

This is a multicenter open-label, single-arm, phase II study designed to investigate the pharmacodynamic and antitumor effects of denosumab alone and in combination with an anti-PD1 agent (pembrolizumab or nivolumab) in patients with unresectable PD-1/PD-L1 inhibitor-naïve regional and distant metastatic melanoma (AJCC stage III/IV). The pharmacodynamic and antitumor effects will be investigated by performing translational research on peripheral blood and tumor tissue collected before and during denosumab alone and in combination with anti-PD-1 treatment.

Full Title of Study: “Phase 2 Study of Denosumab in Combination With a PD-1 Inhibitor in Subjects With Stage III/IV Melanoma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 15, 2023

Detailed Description

STUDY OBJECTIVES Co-primary Objectives – Assess the mechanistic (immune-mediated and/or direct antitumor effect) and pharmacodynamics effect (tissue saturation studies) of denosumab alone (i.e., after three loading doses of denosumab are given on day 1,8 and 22) in patients with unresectable (or resectable) stage III or distant metastatic PD-1/PD-L1 inhibitor-naïve cutaneous melanoma (stage III/IV) by performing translational research on peripheral blood and tumor biopsy samples collected at baseline and after third loading dose of Denosumab. – Assess the immune-mediated and direct antitumor effect of denosumab in combination with anti- PD-1 agent in patients with unresectable (or resectable) stage III or distant metastatic PD-1/PD-L1 inhibitor-naïve cutaneous melanoma (AJCC stage III/IV) by performing translational research on peripheral blood and tumor biopsy samples collected at weeks 16, 28 and 40 of the study and comparing the results with those from baseline and after third loading dose of Denosumab. Secondary Objectives – Assess the safety of the denosumab-anti-PD-1 agent combination in unresectable (resectable) stage III or distant metastatic PD-1/PD-L1 inhibitor-naïve melanoma (AJCC stage III/IV) by NCI-CTCAE v.5.0. – Determine antitumor response by RECIST v1.1 criteria of the denosumab-anti- PD-1 agent combination at 16 weeks in patients with unresectable (resectable) stage III or distant metastatic PD-1/PD-L1 inhibitor-naïve melanoma (AJCC stage III/IV). – Determine the 1-year OS rate of the Denosumab-anti-PD-1 agent combination in patients with unresectable (or resectable) stage III or distant metastatic PD-1/PD-L1 inhibitor-naïve melanoma (AJCC stage III/IV). – Determine the 6-month PFS rate of the denosumab-anti-PD-1 agent combination in patients with unresectable (or resectable) stage III or distant metastatic PD-1/PD-L1 inhibitor-naive melanoma (AJCC stage III/IV). Endpoints Co-primary Endpoints – The immune-mediated mechanism of action of denosumab alone will be evaluated in blood and tumor samples collected at baseline and after third loading dose of denosumab. Multiparameter flow cytometry and ELISA assays will be performed on peripheral blood/serum samples as outlined above in section 1.10.1 Tumor biopsy samples will be evaluated by IHC and IF studies as outlined above in section 1.10.2 (See referenced sections for assay details. The investigators will estimate differences after 3 weeks of denosumab treatment versus baseline). – The immune-mediated mechanism of action of denosumab combined with anti-PD-1 agent will be evaluated in blood and tumor samples collected at weeks 16, 28 and 40 of the study. Multi-parameter flow cytometry and ELISA assays will be performed on peripheral blood/serum samples collected at weeks 16, 28 and 40 as outlined above in section 1.10.1. Tumor biopsy samples obtained at week 16 will be evaluated by IHC and IF studies as outlined above in section 1.10.2 (See referenced sections for assay details. The investigators will describe differences in immunomodulatory/antitumor effects observed with denosumab therapy with later immunomodulatory/antitumor effects observed after the addition of an anti PD-1 agent to denosumab). Secondary Endpoints – AEs experienced by patients receiving denosumab-anti- PD-1 agent will be assessed per NCI-CTCAE v.5.0. – The overall RR (CR + PR) at 16 weeks will assessed based on RECIST v1.1 criteria. – Overall Survival (OS) rate at 1-year is defined as the time from day 1 of study treatment until death as a result of any cause within one year of initiating study treatment. – Progression Free Survival (PFS) rate at 6 months is defined as the time from day 1 of treatment until disease progression or death status measured 6 months after initiating study treatment. Progression events will be defined per RECIST v1.1 criteria. Procedures Subjects in this trial will be given denosumab, 120 mg s.c. q4 weeks, starting on day 1 of study treatment. Additional loading doses of Denosumab will be administered on day 8 and day 22 ( after Amendment 1). Nivolumab, 480 mg will be administered intravenously (IV) every 4 weeks and initiated 21 days after the first dose of Denosumab is given. In subjects enrolled prior to Amendment 1 Pembrolizumab, 200 mg will be administered intravenously (IV) every 3 weeks and initiated 21 days after the first dose of denosumab is given. Combination therapy with both agents will continue as long as subjects benefit from therapy for up to 1 year. Study therapy will be discontinued for intolerable toxicity, disease progression or for other reasons at the discretion of the investigator. If subjects are not withdrawn prematurely then their last dose of study medications will be administered approximately 49 weeks after denosumab was initiated.

Interventions

  • Drug: Denosumab
    • A dose of 120 mg will be administered as a subcutaneous (s.c.) injection every 4 weeks in the upper arm, upper thigh, or abdomen. Another loading dose of 120 mg s.c. denosumab will be administered on day 8. On days when denosumab is administered on the same day as pembrolizumab, the s.c. injection should be given after the infusion of pembrolizumab is completed.
  • Drug: Pembrolizumab
    • Pembrolizumab will be administered as standard of care following the institutional guidelines.The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over approximately 30 minutes (range: 25 – 40 minutes) every 3 weeks until disease progression or unacceptable toxicity.
  • Drug: Nivolumab
    • Nivolumab will be given every four weeks at a dose of 480 mg to be administered as an IV infusion per institutional guidelines.

Arms, Groups and Cohorts

  • Experimental: Single Arm: Denosumab+ PD-1 Inhibitor
    • Subjects in this trial will be given denosumab every 4 weeks, starting on day 1 of study treatment. An additional loading dose of denosumab will be administered on day 8. Subjects who started Pembrolizumab (initiated 21 days after the first dose of denosumab is given) will continue to have it administered intravenously (IV) every 3 weeks. New subjects will receive Nivolumab administered intravenously (IV) every 4 weeks (initiated 21 days after the first dose of denosumab is given). Combination therapy will continue as long as subjects benefit from therapy for up to 1 year.

Clinical Trial Outcome Measures

Primary Measures

  • The antitumor effect of denosumab alone as represented by the change in recent thymic emigrant cells in peripheral blood
    • Time Frame: 3 weeks after start of denosumab
    • The antitumor effect of denosumab alone (i.e., after two loading doses of denosumab are given on day 1 and day 8) in patients with unresectable stage III or distant metastatic Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve cutaneous melanoma (stage III/IV) will be assessed by performing translational research on peripheral blood samples collected at baseline and on day 21 of the study. The hypothesis is that denosumab treatment will prevent destruction of autoreactive T cells within the thymus -and therefore will increase influx of those T cells into the blood, termed recent thymic emigrants (RTE). RTE will be measured by multiparameter flow cytometric analysis of cluster of differentiation (CD)8+ and CD 4+ RTE isolated from peripheral blood. Results will be expressed as the change in number of cells/microliter of peripheral blood between the baseline and the day 21 timepoints.
  • The antitumor effect of denosumab alone as represented by the change in density of tumor-infiltrating cluster of differentiation (CD8+) cells (TILs) in tumor tissue.
    • Time Frame: 3 weeks after start of denosumab
    • The antitumor effect of denosumab alone (i.e., after two loading doses of denosumab are given on day 1 and day 8) in patients with unresectable stage III or distant metastatic Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve cutaneous melanoma (stage III/IV) will be assessed by performing translational research on tumor biopsy samples collected at baseline and on day 21 of the study. The hypothesis is that denosumab alone will increase influx of tumor-infiltrating CD8+ cells (TIL). The density of TILs (number of cells by tumor surface area in mm2) in tumor tissues will be evaluated by Immunohistochemistry (IHC) and Immunofluorescence (IF) studies.
  • The antitumor effect of denosumab combined with anti-PD-1 inhibitor as represented by the change in recent thymic emigrant cells in peripheral blood
    • Time Frame: 16, 28 and 40 weeks after start of denosumab
    • The antitumor effect of denosumab combined with anti-PD-1 inhibitor (Pembrolizumab or Nivolumab) in patients with unresectable stage III or distant metastatic Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve cutaneous melanoma (stage III/IV) will be assessed by performing translational research on peripheral blood samples collected at weeks 16, 28 and 40 of the study. The hypothesis is that denosumab treatment will prevent destruction of autoreactive T cells within the thymus -and therefore will increase influx of those T cells into the blood, termed recent thymic emigrants (RTE). RTE will be measured by multiparameter flow cytometric analysis of cluster of differentiation (CD)8+ and CD 4+ RTE isolated from peripheral blood. Results will be expressed as the change in number of cells/microliter of peripheral blood between the week 16, 28 and 40 timepoints.
  • The antitumor effect of denosumab combined with anti-PD-1 inhibitor as represented by the change in density of tumor-infiltrating cluster of differentiation (CD8+) cells (TILs) in tumor tissue.
    • Time Frame: Baseline, 21 days and 16 weeks after start of denosumab
    • The antitumor effect of denosumab combined with anti-PD-1 inhibitor (Pembrolizumab or Nivolumab) in patients with unresectable stage III or distant metastatic Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve cutaneous melanoma (stage III/IV) will be assessed by performing translational research on tumor biopsy samples collected at baseline, on day 21, and week 16 of the study. The density of TILs (number of cells by tumor surface area in mm2) in tumor tissues will be evaluated by Immunohistochemistry (IHC) and Immunofluorescence (IF) studies.

Secondary Measures

  • Safety of the denosumab- anti-PD-1 inhibitor combination in unresectable stage III or distant metastatic PD-1/PD-L1 inhibitor-naïve cutaneous melanoma
    • Time Frame: 30 days after treatment is discontinued
    • The safety of the denosumab- anti-PD-1 inhibitor (Pembrolizumab or Nivolumab) combination will be assessed by continuous toxicity monitoring focusing on the incidence of serious adverse events (SAEs) with toxicity boundary rules. The NCI Common Terminology Criteria for Adverse Events V5 is a descriptive terminology which will be used for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
  • Overall response rate
    • Time Frame: 16 weeks after start of treatment
    • Antitumor response to the denosumab- anti-PD-1 inhibitor (Pembrolizumab or Nivolumab) combination at 16 weeks in patients with unresectable stage III or distant metastatic PD-1/PD-L1 inhibitor-naïve cutaneous melanoma (AJCC stage III/IV) will be assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) which defines Complete Response (CR) as Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Overall Response Rate (ORR) = CR + PR/total number of subjects.
  • Overall survival rate
    • Time Frame: 1 year from start of study treatment
    • The Overall Survival rate at 1-year is defined as the proportion of subjects still alive from day 1 of study treatment until one year after initiating study treatment
  • Progression free survival rate
    • Time Frame: 6 months from start of study treatment
    • Progression Free survival rate at 6 months is defined as the proportion of subjects without a progression or death event measured from day 1 of treatment until 6 months after initiating study treatment. Progression events will be defined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Participating in This Clinical Trial

Inclusion Criteria

1. Signed written informed consent and HIPAA authorization for release of personal health information. 2. Age ≥ 18 years at the time of consent. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. 4. Histologically confirmed melanoma of cutaneous or mucosal primary; (e.g. sinus, vagina, anus, gastrointestinal tract); metastatic melanomas from unknown primary are allowed because melanoma of unknown primary is biologically similar to cutaneous melanomas. 5. AJCC stage III/IV unresectable (or resectable) disease. Both should be measurable by RECIST v1.1 criteria. Patients with resectable bulky stage IIIB, state IIIC or stage IIID melanoma (≥2-cm in shortest diameter for lymph nodes infiltrated by tumor and ≥2-cm in longest diameter for non-lymph nodes infiltrated by tumor) can also be entered into the study at the discretion of the Principal Investigator. 6. Must have available and consent to collect archived tumor blocks from previous surgeries confirming or treating metastatic disease (e.g. radical lymph node dissection); if not available they can be enrolled into the trial, if they consent to have a tumor biopsy before treatment initiation. 7. Must agree to undergo one on-treatment biopsy on week 4of the study; the biopsy at week 16 is optional. 8. Must agree to have 100 mL blood drawn for study purposes on week 1 , day 20+or-2 (week 4), week 16, week 28, week 40 and end of treatment. 9. Demonstrate adequate organ function, as listed below; all screening labs are to be obtained within 21 days prior to registration.

  • Hemoglobin ≥ 10 g/dL without transfusion or erythropoietin dependency (within 7 days of assessment) – Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 – Absolute Lymphocyte Count (ALC) ≥ 1,000/mm3 – Platelets≥ 100,000/mm3 – Serum Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 × upper limits of normal (ULN) OR – ≥ 60 mL/min using the Cockcroft-Gault formula for subjects with creatinine levels > 1.5 × ULN – Serum Total Bilirubin ≤ 1.5 × ULN or ≤ 2 × ULN for subjects with Gilbert's Syndrome – Aspartate aminotransferase (AST) ≤ 2.5 × ULN OR < 5 × ULN for subjects with liver metastases – Alanine aminotransferase (ALT) ≤ 2.5 × ULN OR < 5 × ULN for subjects with liver metastases – Albumin ≥ 2.5 mg/dL – Serum calcium ≥ 2.0 mmol/L (8.0 mg/dL) 10. Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to study treatment. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. 11. Females of childbearing potential must be willing to use an adequate methods of contraception, as outlined in the protocol. Oral contraception is required 14 days prior to initiation of study medications until 120 days after treatment discontinuation. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 12. Male patients with female partners must have had a prior vasectomy or agree to use an adequate method of contraception as outlined in the protocol- Contraception, starting with the first dose of study therapy through 150 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 13. As determined by the enrolling physician or protocol designee, willingness and ability of the subject to understand and comply with study procedures. 14. Previous radiation therapy is allowed, provided it is completed ≥14 days prior to starting denosumab and patient has recovered adequately from any related toxicities (grade≤1, or grade ≤2 that is stable for ≥3 months). 15. If patient has received adjuvant treatments, in particular ipilimumab and high dose interferon, any toxicities must have resolved to grade 1 or less. Grade 2 toxicities attributed to ipilimumab from autoimmune endocrinopathies that require permanent hormone replacement therapy are allowed as long as they are adequately treated. This implies that patients should be off systemic steroids for treatment of any of these or other autoimmune toxicities (e.g. colitis, rash). Subjects who have previously received PD-1 inhibitors in stage III (adjuvant) or stage IV are allowed as long as: 1. the interval between the last dose of the adjuvant PD-1 inhibitor and the date of relapse (clinical or radiographic) is at least 1 year, 2. if subjects who received treatment for stage IV had antitumor response (partial response or complete response) by RECIST criteria version 1.1 but they stopped due to subject/investigator preference for at least a year between the last dose of the PD-1 inhibitor and the date of relapse (clinical or radiographic). Allowing for these subjects who have previously received PD-1 inhibitors in the adjuvant setting (i.e. no knowledge about clinical benefit) or following definite antitumor response in the metastatic setting is based on a recent case series of subjects who responded to PD-1 inhibitor rechallenge, if they had previously responded to PD-1 inhibitors. This implies that waning antitumor immunity in the absence (i.e. >1 year) of costimulation with PD-1 inhibitors may be the reason for cancer recurrence and NOT primary resistance of PD-1 inhibitors. 3. any side effects that may have occurred during the previous exposure to PD-1 inhibitors are not serious (i.e. grade 1 or 2 by CTCAE version 5.0 criteria). Exclusion Criteria:

1. History of prior malignancy, with the exception of the following:

  • Non-melanoma skin cancers, non-invasive bladder cancer, and carcinoma in situ of the cervix, – Prior history of prostate, provided that patient is not under active systemic treatment other than hormonal therapy and with documented undetectable prostate specific antigen (PSA < 0.2 ng/mL), – Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) provided patient has isolated lymphocytosis (Rai stage O), and does not require systemic treatment [for "B" symptoms, Richter's transformation, lymphocyte doubling time (< 6 months), lymphadenopathy or hepatosplenomegaly], – Lymphoma or any type or hairy-cell leukemia, provided patient is not on an active systemic treatment and is in complete remission, as evidenced by Positron Emission Tomography (PET)/CT scans and bone marrow biopsies for at least 3 months, – History of other malignancy, provided patient has completed therapy, or does not require therapy, and is free of disease for ≥ 2 years. If patient has had other malignancy within the last 2 years from which he/she may have been completely cured by surgery alone, or does not require any treatment other than observation at the specialist's discretion, he/she may considered to be enrolled on condition that the risk of development of recurrent or distant metastatic disease based on the American Joint Committee in Cancer (AJCC) staging system is less than 30% in 3 years from the original diagnosis of other malignancy. 2. Has known active central nervous system (CNS) metastases that are symptomatic and require antiepileptic drugs or corticosteroids (any dose). Subjects with previously treated brain metastases may participate provided they are asymptomatic (i.e., no neurologic symptoms) for at least 2 weeks prior to the first dose of trial treatment and are not using steroids for at least 7 days prior to trial treatment. Patients with previously treated brain metastases should have evidence of stable brain metastases (without evidence of progression by imaging) for at least 2 weeks prior to the first dose of trial treatment. Patients with previously treated but grown brain metastases (or new brain metastases if there is no prior history of brain metastases) are still allowed in the study as long as the net growth of pre-existing brain lesions (or new brain lesions if there is no prior history of brain metastases) does not exceed 1-cm in largest diameter as measured by brain MRI with IV contrast (for example, a patient with pre-existing brain lesion(s) that has grown by 6-mm in the largest diameter and also has a new lesion that measures 4-mm in largest diameter can still be enrolled in the study; alternatively, a patient that has a new brain lesion that measures 1-cm in the largest diameter and no growth of pre-existing brain lesions can still be enrolled in the study). This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability. Subjects with leptomeningeal disease, detected either by brain MRI or by cytology (e.g. lumbar puncture) are also excluded. 3. Treatment with any investigational drug, immunotherapy or chemotherapy within 28 days prior to study treatment (i.e., initiation of denosumab). Treatment with any targeted therapy (e.g. Mitogen-Activated Protein Kinases (MAPK) inhibitors) is allowed as long as at least 15 days have elapsed since last dose of drug. 4. Patients discontinuing prior therapy with tyrosine kinase inhibitors for melanoma should be off these medications for at least 15 days before starting study treatment. 5. Prior PD-1/PD-L1 therapies in the adjuvant setting; targeted therapies or prior ipilimumab in the adjuvant setting are allowed. 6. Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk, if he/she were to participate in the study. This includes, but is not limited, to serious medical conditions or psychiatric illness likely to interfere with participation in this clinical study. 7. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy equivalent to daily doses of prednisone of 10 mg or greater (or an equivalent dose of other corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 8. Has a known history of active tuberculosis (Mycobacterium Bacillus Tuberculosis). 9. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 10. Hypersensitivity to nivolumab, pembrolizumab or denosumab or any of their excipients. 11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 12. Has a history of non-infectious pneumonitis that required systemic corticosteroids or evidence of interstitial lung disease or current active, non-infectious pneumonitis Episodic, brief (< 7 day) exposure to systemic corticosteroids (e.g. steroid taper for poison ivy or COPD exacerbation) is allowed. 13. Has a history of an acute coronary event (e.g. myocardial infarction) within 3 months since study entry, uncontrolled and symptomatic coronary artery disease, or congestive heart failure New York Heart Association class III/IV. 14. Has an active infection requiring systemic therapy within 7 days prior to treatment initiation. 15. Has a known history of Human Immunodeficiency Virus (HIV 1/2 antibodies). 16. Known serologic status reflecting active hepatitis B or C infection. Patients that are hepatitis B core antibody positive, but antigen negative, will need a negative polymerase chain reaction (PCR) prior to enrollment. [Note: Hepatitis B antigen or PCR positive patients will be excluded]. 17. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed. 18. Known active metabolic bone disease such as Paget's disease, Cushing's disease, hyperprolactinemia, over the last year 12 months, known history of osteoporosis that is symptomatic (e.g. history of fractures, bone pain), or hypercalcemia/hypocalcemia of any type (serum-free calcium being more than 1.1 x upper limit of normal (ULN) and less than 0.9 x, lower limits normal. LLN) over the last 2 weeks since study initiation that requires treatment beyond calcium and vitamin D supplementation. 19. Prior treatment with denosumab. Use of bisphosphonates for the treatment of metastatic bone disease, but not for hypercalcemia of malignancy, is allowed. 20. History of current evidence of osteonecrosis or osteomyelitis of the jaw. Note: The subject should be referred to dentist before study treatment initiation for poor dentition or other dental issues that, in the opinion of the treating physician, may increase the risk of osteonecrosis of the jaw.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 99 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • UNC Lineberger Comprehensive Cancer Center
  • Collaborator
    • Amgen
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Stergios Moschos, MD, Principal Investigator, UNC Lineberger Comprehensive Cancer Center

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