Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma, Hormone Receptor Positive HER2 Negative Metastatic Refractory Breast Cancer or Stage III-IV Non-Small Cell Lung Cancer

NCT05098210 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1121642NCI-2021-1019910668
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the safety of personalized neo-antigen peptide vaccine in treating patients with stage IIIC-IV melanoma, hormone receptor positive HER2 negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or does not respond to treatment (refractory) or stage III-IV non-small cell lung cancer. Personalized neo-antigen peptide vaccine is a product that combines multiple patient specific neo-antigens. Given personalized neo-antigen peptide vaccine together with Th1 polarizing adjuvant poly ICLC may induce a polyclonal, poly-epitope, cytolytic T cell immunity against the patient's tumor.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Locally Advanced Cutaneous Melanoma; Locally Advanced Mucosal Melanoma; Metastatic Acral Melanoma; Metastatic Conjunctival Melanoma; Metastatic Cutaneous Melanoma; Metastatic HER2-Negative Breast Carcinoma; Metastatic Hormone Receptor-Positive Breast Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Mucosal Melanoma; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Recurrent Cutaneous Melanoma; Recurrent HER2-Negative Breast Carcinoma; Recurrent Hormone Receptor-Positive Breast Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Recurrent Mucosal Melanoma; Stage III Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Unresectable Acral Melanoma; Unresectable Cutaneous Melanoma; Unresectable Lung Non-Small Cell Carcinoma; Unresectable Mucosal Melanoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Will be assessed by Common Terminology Criteria for Adverse Events version 5.0.

  1 year post first vaccination

Secondary Outcomes (6)

• Number of formulated and administered personalized neo-antigen vaccines

  Week 48

• Number of formulated personalized neo-antigen vaccines with at least five (5) vaccine peptides

  Week 48

• Number of formulated personalized neo-antigen vaccines in less than 16 weeks since screening visit biopsy

  16 weeks

• Evaluation of target lesion

  At 1 year post first vaccination

• Best overall response

  1 year post first vaccination

Study Arms (1)

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

EXPERIMENTAL

Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.

Biological: Neoantigen Peptide Vaccine; Biological: Nivolumab; Drug: Poly ICLC; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Positron Emission Tomography

Interventions

Neoantigen Peptide Vaccine BIOLOGICAL

Given IM

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

Poly ICLC DRUG

Given IM

Also known as: Hiltonol, Poly I:Poly C with Poly-L-Lysine Stabilizer, poly-ICLC, PolyI:PolyC with Poly-L-Lysine Stabilizer, Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose, Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose, Stabilized Polyriboinosinic/Polyribocytidylic Acid

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: MUGA Scan

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: Bx

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT Scan, CT Scan, Computed Axial Tomography

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

Positron Emission Tomography PROCEDURE

Undergo PET or PET/CT

Also known as: PET scan

Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and/or male patients age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Patients must have at least 1 lesion (or aggregate lesions) to obtain tumor tissue for resection of \>= 1 cm or \>= 4 core biopsies acceptable. Amenable to image (CT, ultrasound \[U/S\], or magnetic resonance imaging \[MRI\]) guided biopsy for tissue collection necessary for neoantigen identification. Either primary or metastatic sites are options for tissue collection
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: Participants must have measurable disease, defined as at least one target lesion that can be measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm, unless lymph node in which case short axis must be \>= 15 mm. Baseline imaging (for example diagnostic CT chest/abdomen/pelvis, PET CT scan and imaging of the affected extremity as appropriate), brain imaging (MRI or CT scan) must be obtained within 45 days of prior to start of first planned vaccine dose infusion. MRI can be substituted for CT in patients unable to have CT contrast
• Serum creatine \< 1.5 mg/dL or estimated glomerular filtration rate (eGFR) \> 60 mL/min
• Total bilirubin (tBili) \< 1.5 x upper limit of normal (ULN) and an aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 2.5 x ULN and \< 5 x ULN for subjects with documented liver metastasis. Patients with suspected Gilbert syndrome may be included if tBili \> 3 but no other evidence of hepatic dysfunction
• =\< grade 1 dyspnea and arterial oxygen saturation (SaO2) \>= 92% on ambient air. If pulmonary function tests (PFTs) are performed based on the clinical judgement of the treating physician, patients with forced expiratory volume in 1 second (FEVI) \>= 70% of predicted and carbon monoxide diffusing capability (DLCO) (corrected) of \>= 60% of predicted will be eligible
• Patients with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids will be excluded
• Patients 60 years of age or older are required to have left ventricular ejection fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be established with echocardiogram or MUGA scan, and left ejection fraction must be \>= 50%. Cardiac evaluation for other patients is at the discretion of the treating physician
• Subjects with a history of myocarditis or congestive heart failure (as defined by New York Heart Association functional classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry will be excluded
• Absolute neutrophil count (ANC) \> 1000 cells/mm\^3
• Hemoglobin \>= 9 mg/dL
• Platelet count \>= 50,000/uL
• Toxicity from prior therapy must be recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5 grade 2 or less
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures

You may not qualify if:

• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 5 months after the last dose of investigational product
• Any history of an immune-related grade 4 adverse event attributed to prior cancer immunotherapy CIT (other than endocrinopathy managed with replacement therapy or asymptomatic elevation of serum amylase or lipase)
• Any history of an immune-related grade 3 adverse event attributed to prior CIT that required permanent discontinuation of PD-1 inhibitor therapy
• Immune-related adverse events related to prior CIT (other than endocrinopathy managed with replacement therapy or stable vitiligo) that have not resolved to baseline. Patients treated with corticosteroids for immune-related adverse events must demonstrate absence of related symptoms or signs for \>= 4 weeks following discontinuation of corticosteroids
• Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated \> 4 weeks prior to enrollment. Patients should be recovered from the effects of radiation
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed
• Patients with known symptomatic brain metastases. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable for \>= 1 months (confirmed by magnetic resonance imaging \[MRI\])
• Patients with rapidly progressing disease, symptomatic visceral disease, or patients who are expected to have rapidly progressive disease over the course of several months despite bridging therapy approved by the protocol
• Known primary immunodeficiencies, either cellular (e.g., DiGeorge syndrome, T-negative severe combined immunodeficiency \[SCID\]) or combined T- and B-cell immunodeficiencies (e.g., T- and B-negative SCID, Wiskott-Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency)
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation
• Known positive test for HIV infection
• Patients with active infection causing fever (temperature \> 38.1 degrees Celsius \[C\]) or subjects with unexplained fever (temperature \> 38.1 degrees C) may not receive the investigational product unless the fever is =\< 38.1 for 5 days prior to start
• Active uncontrolled infection: individuals with a history of hepatitis C who have successfully completed antiviral therapy with an undetectable viral load, and those with hepatitis B who have, per standard practice, hepatitis well-controlled on medication (e.g., AST and ALT \< 5 x ULN) can be included
• History of autoimmune disease that has not been controlled with treatment in the last 12 months, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions: Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., no psoriatic arthritis) may be eligible
• Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone \> 10 mg/day or equivalent, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNF-alpha antagonists) within 2 weeks prior screening. The use of topical, eye drops, local injections, or inhaled corticosteroids (e.g. fluticasone for chronic obstructive pulmonary disease) is allowed. The use of oral mineralocorticoids (e.g. fludrocortisone for patients with orthostatic hypotension) is allowed. Physiologic doses of corticosteroids for adrenal insufficiency are allowed. Low dose corticosteroids for a short duration \[5 mg once daily (QD) prednisone for 2 weeks\] as symptomatic treatment and upon with discussion with the investigator is allowed. Note: Patients with adrenal insufficiency may take 10 mg of prednisone or equivalent daily

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Amazon, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Lung Neoplasms

Interventions

Nivolumab; poly ICLC; Biopsy; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Joshua Veatch

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

FHCC Intake

CONTACT

206-606-1024; hutchdoc@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 28, 2021
• Study Start: June 9, 2022
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)