NeoVax Plus Ipilimumab in Renal Cell Carcinoma

A Phase I Study Combining NeoVax, a Personalized NeoAntigen Cancer Vaccine, With Ipilimumab to Treat High-risk Renal Cell Carcinoma

This research study is evaluating a new type of Kidney Cancer vaccine called "Personalized NeoAntigen Cancer Vaccine"as a possible treatment for Kidney Cancer.

The following intervention will be involved in this study:

• Personalized Neoantigen Vaccine
• Poly-ICLC (Hiltonol)
• Ipilimumab

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Cancer
• Intervention / Treatment: Drug: NeoVax; Drug: Ipilimumab

Detailed Description

This research study is a Phase I clinical trial, which tests the safety of an investigational kidney cancer vaccine and also tries to define the appropriate dose of the investigational kidney cancer vaccine to use for further studies. "Investigational" means that the kidney cancer vaccine, in this case the Personalized Neoantigen Cancer Vaccine, is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not approved the Personalized Cancer Vaccine for any use in patients, including people with kidney cancer.

Poly-ICLC (also called Hiltonol) is an experimental "viral mimic" and an activator of immunity. Poly-ICLC is an investigational drug, meaning the FDA has not approved it as a treatment for any disease.

Personalized NeoAntigen Cancer Vaccine: The purpose of this study is to determine if it is possible to make and administer safely a vaccine against kidney cancer by using information gained from specific characteristics of the participant's own kidney cancer. It is known that kidney cancers have mutations (changes in genetic material) that are specific to an individual patient and tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the participant's body fight any tumor cells that could cause the kidney cancer to come back in the future. The study will examine the safety of the vaccine when given at several different time points and will examine the participant's blood cells for signs that the vaccine induced an immune response.

Ipilimumab (Yervoy™) is an antibody that has been approved by the United States Food and Drug Administration (FDA) for the treatment of melanoma.

In this research study, the investigators are looking at the safety and tolerability of the Personalized NeoAntigen Cancer Vaccine combined with Ipilimumab as well as the body's immune response to the vaccine. Ipilimumab will be delivered as an injection given underneath the skin rather than injected in the vein in proximity to each vaccination site in order to 1) direct anti-CTLA4 activity to the vaccine-draining lymph nodes and 2) limit potential toxic effects.

• Study Type: Interventional
• Enrollment (Estimated): 19
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Patrick Ott, MD; Phone Number: 617-632-5456; Email: pott@partners.org
• Study Contact Backup: Name: Toni Choueiri, MD; Phone Number: 617-632-5456

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for Initial Registration:

• Ability to understand and the willingness to sign a written informed consent document.
• Patients should have suspected stage III or stage IV clear cell renal cell carcinoma (ccRCC), with anticipation that all disease can be surgically resected. Confirmation of clear cell histology, final stage (III or IV), and removal of all disease will be done after the surgery, and will be required for further participation of the trial.
• Patient is agreeable to allow tumor and normal tissue samples to be submitted for complete exome and transcription sequencing.
• Patients undergoing a potentially curative metastatectomy are eligible if the tumor tissue from the surgery is enough to make a vaccine.
• ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.
• Age ≥ 18 years.

• Participants must have normal organ and marrow function as defined below:

  • leukocytes ≥3,000/mcL (microliter)
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • AST (SGOT) /ALT (SGPT) ≤2.5 × institutional upper limit of normal
  • creatinine clearance ≥40 mL/min/(calculated using the Cockroft-Gault equation)
• Women of childbearing potential (WOCBP) must have a negative pregnancy test (minimum sensitivity 25 IU/L or equivalent of HCG) before entry onto the trial and within 7 days prior to start of study medication, because the effects NeoVax on the developing human fetus are unknown. It is the investigators' responsibility to repeat the pregnancy test should start of treatment be delayed.
• Female patients enrolled in the study, who are not free from menses for >2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity for the duration of treatment with ipilimumab plus 5 half-lives of ipilimumab (75 days) plus 30 days (duration of ovulatory cycle) for a total of 105 days post-treatment completion. Approved contraceptive methods include for example: intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.
• Male patients must agree to use an adequate method of contraception for the duration of treatment with study drugs plus 5 half-lives of the study drug (75 days) plus 90 days (duration of sperm turnover) for a total of 165 days post-treatment.

Eligibility Criteria for Secondary Registration

• ECOG performance status ≤1.

• Participants must have normal organ and marrow function as defined below:

  • leukocytes ≥3,000/mcL
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
  • creatinine ≥40 mL/min/(calculated using the Cockroft-Gault equation)
• Patients must have histologically confirmed clear cell renal cell carcinoma (ccRCC), stage III or fully resected stage IV (no evidence of disease), before starting study drugs per AJCC 8th edition.
• No evidence of disease (NED) at secondary registration.
• Women of childbearing potential (WOCBP) must have a negative pregnancy test (minimum sensitivity 25 IU/L or equivalent of HCG) within 7 days prior to start of study medication, because the effects NeoVax on the developing human fetus are unknown. It is the investigators' responsibility to repeat the pregnancy test should start of treatment be delayed.
• Female patients enrolled in the study, who are not free from menses for >2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity throughout the study, starting with visit 1 through 4 weeks after the last dose of study therapy. Approved contraceptive methods include for example; intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception.
• Male patients must agree to use an adequate method of contraception for the duration of treatment with study drugs plus 5 half-lives of the study drug (75 days) plus 90 days (duration of sperm turnover) for a total of 165 days post-treatment.

Exclusion Criteria:

• Prior treatment with immune-modulatory agents including, but not limited to: IL-2, CTLA-4 blockade, PD-1/PD-L1 blockade, CD40 stimulation, or CD137 stimulation.
• Prior investigational ccRCC-directed cancer vaccine therapy.
• Patients with active brain metastases or leptomeningeal disease.
• Prior systemic therapy, including targeted therapy such as VEGF or mTOR inhibitors unless it is >6 months between last dose of drug and first vaccination with NeoVax. Systemic therapy is allowed only if prior therapy was not immune therapy (i.e. VEGF TKI), and it was >6 months ago.
• Treatment with other investigational products within the last 2 months prior to entry into this study.
• Previous bone marrow or stem cell transplant.
• Concomitant therapy with any anti-cancer agents for ACTIVE cancer treatment, other investigational anti-cancer therapies, or immunosuppressive agents; chronic use of systemic corticosteroids with prednisone >10 mg/day.
• Use of a non-oncology vaccine therapy for prevention of infectious diseases (with the exception of vaccination against the SARS-CoV-2 virus for the prevention of COVID-19 disease) is not allowed for 4 weeks prior to day 1, until 8 weeks after last study dose. Given the severity of the COVID-19 pandemic, vaccination specifically against the SARS-CoV-2 virus for the prevention of COVID-19 is ALLOWED in this study.
• History of severe allergic reactions attributed to any vaccine therapy for the prevention of infectious diseases.
• History of or current active autoimmune diseases, [e.g. including but not limited to inflammatory bowel diseases [IBD], rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome). Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary.].
• Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
• Concomitant treatment with corticosteroids greater than physiologic doses (used in the management of cancer or non-cancer-related illnesses). Topical (if not including the proposed vaccination sites) or inhalational steroids are allowed.
• Known chronic infections with HIV, hepatitis B or C.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
• History of current immunodeficiency disease [e.g., splenectomy or splenic irradiation].
• Any underlying medical condition, psychiatric condition or social situation that in the opinion of the investigator would compromise study administration as per protocol or compromise the assessment of AEs.
• Pregnant women are excluded from this study because personalized neoantigen peptides and poly-ICLC are agents with unknown risks to the developing fetus. Because there is an unknown but potential risk of adverse events in nursing enfants secondary to treatment of the mother with personalized neoantigen peptides and poly-ICLC, nursing women are excluded from this study.
• Individuals with a history of another invasive malignancy are ineligible except for the following circumstances: a) individuals with a history of invasive malignancy are eligible if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; b) individuals with any of the following cancers are eligible if diagnosed and treated: carcinoma in situ of the breast, oral cavity or cervix and basal cell or squamous cell carcinoma of the skin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neovax in Combination with Ipilimumab; Patients will undergo surgery with the intent to resect the primary kidney tumor Neovax is a combination of Poly-ICLC and Neoantigen Peptides Priming doses of NeoVax will be administered on days 1, 4, 8, 15, and 22; In the boost phase, vaccine will be administered on days 78 (week 12) and 134 (week 20 Ipilimumab will be injected within 1 cm of each NeoVax administration	Drug: NeoVax; combination of Neoantigen peptides and poly-ICLC; Other Names: neoantigen vaccine; Drug: Ipilimumab; local administration of ipilimumab; Other Names: Yervoy
Experimental: NeoVax alone; Patients will undergo surgery with the intent to resect the primary kidney tumor Neovax is a combination of Poly-ICLC and Neoantigen Peptides Priming doses of NeoVax will be administered on days 1, 4, 8, 15, and 22; In the boost phase, vaccine will be administered on days 78 (week 12) and 134 (week 20)	Drug: NeoVax; combination of Neoantigen peptides and poly-ICLC; Other Names: neoantigen vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with dose-limiting toxicity (DLT) experienced within 49 days (7 weeks) of treatment initiation as assessed by CTCAE v4.0	49 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with NeoVax induced IFN γ (interferon γ) T-cell Response against neoepitopes measured by ELISPOT at week 16	16 weeks
Number of participants alive at 2 years	2 years

Collaborators and Investigators

• Sponsor: Patrick Ott, MD, PhD
• Collaborators: Bristol-Myers Squibb; Oncovir, Inc.
• Investigators: Principal Investigator: Patrick Ott, MD, Dana-Farber Cancer Institute; Principal Investigator: Toni Choueiri, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: September 8, 2016
• First Submitted That Met QC Criteria: October 28, 2016
• First Posted (Estimated): November 1, 2016

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Kidney Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Neoplasms; Carcinoma, Renal Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: 16-097

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No