CAVATAK® and Ipilimumab in Uveal Melanoma Metastatic to the Liver (VLA-024 CLEVER)

NCT03408587 | Completed Phase 1 FDA Drug

• 2 other identifiers: V937-010VLA-024
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label Phase 1b clinical study of ipilimumab in combination with intravenous CVA21 in subjects who have uveal melanoma metastatic to liver.

Conditions

Uveal Melanoma; Liver Metastases

Keywords

CVA21; CAVATAK; Coxsackievirus; ocular; eye; ipilimumab; yervoy; oncolytic; virus; checkpoint; CTLA-4

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-related adverse events as assessed using the current NCI-CTCAE.

  Treatment-emergent adverse events (TEAEs) are defined as AEs that start on or after the first day of study treatment and within 30 days of the last administration of study treatment. The incidence of TEAEs will be summarized based on the number and percentage of subjects who experience events classified by MedDRA system organ class and preferred term.

  30 days from the last administration of study treatment

Secondary Outcomes (1)

• Overall Response Rate

  2 years

Study Arms (1)

CVA21 / Ipilimumab

EXPERIMENTAL

Subjects will receive up to 8 cycles (Day 155) of intravenous CVA21 and 4 doses of ipilimumab (Days 8, 29, 50 and 71).

Biological: CVA21; Biological: Ipilimumab

Interventions

CVA21 BIOLOGICAL

Oncolytic virus

Also known as: CAVATAK, Coxsackievirus A21

CVA21 / Ipilimumab

Ipilimumab BIOLOGICAL

Fully human IgG1 monoclonal antibody that binds to the CTLA-4 receptor expressed on activated T cells.

Also known as: Yervoy

CVA21 / Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Histologic or cytologically confirmed diagnosis of uveal melanoma with measurable disease (based on RECIST 1.1 criteria) in the liver (by CT, PET/CT or MRI) at the time of screening.
• Patients that have had prior treatment must show disease progression during or following the last treatment according to RECIST 1.1 criteria.
• Men and women ≥ 18 years of age.
• The subject has a life expectancy of greater than 12 weeks.
• The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ function as defined by and obtained within 28 days of starting treatment:
• Absolute neutrophil count ≥ 1,500 /mcl
• WBC ≥ 3.0 x 10e9/L
• Platelets ≥ 100,000 /mcl
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 1.5 x ULN
• Albumin \> 3 g/dL
• Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for subjects with total bilirubin \> 1.5 x ULN
• AST and ALT ≤ 5 x ULN
• INR or PT ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT and PTT are within therapeutic range of intended use of anticoagulants.

You may not qualify if:

• The subject is a candidate for surgery or loco-regional treatment with curative intent.
• Subjects with active (i.e. symptomatic or growing) central nervous system (CNS) metastases. Subjects with CNS metastases are eligible if the metastases have been treated with surgery and/or radiotherapy, the subject is off corticosteroids for at least 2 weeks and the subject is neurologically stable.
• Known additional malignancy that is progressing or requires active treatment. Exceptions include cutaneous squamous cell or basal cell carcinoma that has undergone potentially curative therapy or in-situ cervical cancer.
• Known history of Human Immunodeficiency Virus (HIV, HIV 1/2 antibodies), known active Hepatitis B (e.g. HBsAg reactive) or Hepatitis C (e.g. HCV RNA \[qualitative\] is detected).
• Current systemic steroid therapy other than physiologic replacement (i.e. prednisone ≤ 10 mg or equivalent). Inhaled or topical steroid use is allowed.
• Active auto-immune 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 allowed.
• Active colitis or previous immune-mediated colitis that has not resolved to grade 1 or less.
• Chemotherapy, targeted small molecule therapy, radiation therapy, hormonal treatment or immunotherapy within 21 days prior to initiation of treatment. A 6-week washout period will be required for those with prior PD-1 or PD-L1 treatment. Subjects must have resolution of toxic effect(s) of the most recent therapy to Grade 1 or less. Exceptions are subjects with ≤ Grade 2 alopecia or ≤ Grade 2 neuropathy who are permitted in the study. If the subject received major surgery or radiation therapy of \>30 Gy, they must have recovered from the toxicity and/or any complications from the intervention.
• Pregnancy, breastfeeding, or expectation to conceive or father children within the projected duration of the trial, starting with the screening visit through 4 weeks after the last dose of study treatment.
• Known sensitivity to any of the products or components to be administered during dosing.
• Participation in a study of an investigational agent or device within 4 weeks of Day 1.
• Subjects with any other concurrent, uncontrolled illness, including known psychiatric or substance abuse disorders which may interfere with the ability of the subject to cooperate and participate in the trial. Other examples of such conditions would include unstable angina, myocardial infarction (MI) or cerebrovascular accident (CVA) within 6 months of study entry.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Patients with tumors lying close to an airway, major blood vessel or spinal cord that, in the opinion of the investigator, could cause occlusion or compression in the case of swelling, or erosion into a major vessel in the case of necrosis.

Sponsors & Collaborators

• Viralytics: lead

Study Sites (3)

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Lutzky J, Sullivan RJ, Cohen JV, Ren Y, Li A, Haq R. Phase 1b study of intravenous coxsackievirus A21 (V937) and ipilimumab for patients with metastatic uveal melanoma. J Cancer Res Clin Oncol. 2023 Aug;149(9):6059-6066. doi: 10.1007/s00432-022-04510-3. Epub 2023 Jan 18.

  PMID: 36651961 RESULT

MeSH Terms

Conditions

Uveal Melanoma; Coxsackievirus Infections; Virus Diseases; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Infections

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jose Lutzky, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 10, 2018
• First Posted: January 24, 2018
• Study Start: January 29, 2018
• Primary Completion: May 22, 2019
• Study Completion: May 22, 2019
• Last Updated: May 6, 2023

Record last verified: 2023-05

Locations

US (3)