A Study of Combination with TBI-1401(HF10) and Ipilimumab in Japanese Patients with Unresectable or Metastatic Melanoma

NCT03153085 | Completed Phase 2 DMC

• 1 other identifier: TBI1401-02
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study is to determine if TBI-1401(HF10) in combination with ipilimumab is effective in Japanese patients with stages IIIB, IIIC, or IV unresectable or metastatic melanoma.

Conditions

Melanoma Stage III; Melanoma Stage IV

Keywords

Unresectable melanoma; Metastatic melanoma; Recurrent Melanoma; TBI-1401(HF10); HF10; HSV-1; Oncolytic virus; Oncolytic viral immunotherapy; Ipilimumab; Intratumoral administration; canerpaturev

Outcome Measures

Primary Outcomes (1)

• Best overall response rate (BORR) by irRC

  Determine the efficacy of TBI-1401(HF10) in combination with Ipilimumab evaluated by irRC (immuno-related response criteria)

  at 24 weeks

Secondary Outcomes (9)

• Best overall response rate (BORR) by mWHO response criteria

  at weeks 24

• Best overall response rate (BORR) by RECIST version 1.1

  at weeks 24

• Objective response rate (ORR) by irRC

  at weeks 6, 12, 18, and 24

• Objective response rate (ORR) by mWHO

  at weeks 6, 12, 18, and 24

• Objective response rate (ORR) by RECIST version 1.1

  at weeks 6, 12, 18, and 24

Other Outcomes (3)

• Levels of antibody to HSV-1

  up to weeks 24

• Change in immunologic parameters in serum

  up to weeks 24

• Histopathological response with TBI-1401(HF10) administrated tumor

  up to weeks 24

Study Arms (1)

TBI-1401(HF10) + Ipilimumab

EXPERIMENTAL

1x10\^7 TCID50/mL TBI-1401(HF10) administered to a single or multiple eligible tumors in a total volume up to 5.0 mL (injection volume will be adjusted based on the size of tumor mass) by intratumoral injection and 3 mg/kg ipilimumab administered by intravenous infusions.

Biological: TBI-1401(HF10); Drug: Ipilimumab

Interventions

TBI-1401(HF10) BIOLOGICAL

1x10\^7 TCID50/mL TBI-1401(HF10) (for a total of 6 injections; the first 4 injections at 1-week intervals; the remaining 2 injections at 3-week intervals). Following combination therapy, patients may continue to receive the 1x10\^7 TCID50/mL TBI-1401(HF10) alone for up to an additional 13 injections (total of 19 injections = 1 year) if eligible for administration.

Also known as: HF10, canerpaturev

TBI-1401(HF10) + Ipilimumab

Ipilimumab DRUG

3 mg/kg ipilimumab (for a total of 4 intravenous infusions, each administered at 3-week intervals).

Also known as: anti CTLA-4 antibody

TBI-1401(HF10) + Ipilimumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed Stage IIIB, IIIC or IV unresectable or metastatic melanoma except uveal melanoma, who must have a history of treatment (chemotherapy, molecular targeted therapy, or anti PD-1 antibody therapy).
• Patients must have measurable non-visceral lesion(s) that are evaluable by the modified World Health Organization (mWHO) criteria and immune-related response criteria (irRC).
• Patients must be ≥ 20 years of age.
• Patients must have a life expectancy ≥ 24 weeks.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Patients must have adequate organ function, defined as
• Total bilirubin levels ≤ 1.5 x upper limit of normal \[ULN\] (except for patients with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL)
• AST/ALT levels ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.
• Creatinine ≤ 1.5 x ULN or creatinine clearance (calculated) ≥ 60 mL/min/1.73 m\^2 for patients with creatinine \> 1.5 x ULN.
• Absolute neutrophil count ≥1,500/µL and
• Platelet count ≥ 75,000/ µL
• Men and women of childbearing potential must agree to use adequate contraception from the time of consent through 30 days after final study treatment.
• Females of childbearing potential must have a negative urine or serum pregnancy test within 1 week prior to start of treatment.
• Patients must be able to understand and willing to sign a written informed consent document.

You may not qualify if:

• Patients who were previously treated with ipilimumab by intravenous infusion.
• Patients receiving chemotherapy or molecularly targeted drug or anti-PD-1 antibody treatment or radiotherapy or immunotherapy within 4 weeks prior to initiating study treatment.
• Patients with a history of Grade 4 adverse events caused by chemotherapy, molecularly targeted drug, anti-PD-1 antibody treatment, radiotherapy or immunotherapy conducted more than 4 weeks prior to TBI-1401(HF10) treatment, or presence of such adverse events of Grade 2 or greater, except alopecia and adverse events controlled by a treatment.
• Patients receiving anti-herpes medication within 1 week prior to initiating TBI-1401(HF10) administration, except local treatment such as ointment.
• Patients with a history of significant tumor bleeding, or coagulation or bleeding disorders.
• Patients with target tumors that could potentially invade a major vascular structure (e.g., innominate artery, carotid artery), based on unequivocal imaging findings.
• Patients with Grade 2 or greater neurologic abnormalities (CTCAE version 4.0), including Grade 2 or greater peripheral neuropathy caused by previous treatments.
• Patients with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C virus (HCV), or Epstein-Barr virus (EBV) infection.
• Patients requiring systemic glucocorticoid (except 10 mg/day/body prednisolone or less) or immunosuppressive therapy because of the presence or history of autoimmune disease (e.g., Crohn's disease, ulcerative colitis) or other diseases.
• Concurrent use of any other investigational agents within 4 weeks prior to initiating study treatment.
• Patients with active CNS metastases or carcinomatous meningitis, except patients with CNS lesions that have been treated and have no evidence of progression in the brain on CT/MRI for ≥ 3 months.
• Pregnant or breastfeeding women (excluding the case in which breastfeeding is discontinued and will not resume it); women desiring to become pregnant within the timeframe of the study are also excluded.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, as determined by the investigator.

Sponsors & Collaborators

• Takara Bio Inc.: lead

Study Sites (12)

Clinical Site

Nagakute, Aichi-ken, Japan

Location

Clinical Site

Nagoya, Aichi-ken, Japan

Location

Clinical Site

Fukuoka, Fukuoka, Japan

Location

Clinical Site

Kurume, Fukuoka, Japan

Location

Clinical Site

Sapporo, Hokkaido, Japan

Location

Clinical Site

Tsukuba, Ibaraki, Japan

Location

Clinical Site

Kumamoto, Kumamoto, Japan

Location

Clinical Site

Niigata, Niigata, Japan

Location

Clinical Site

Osaka, Osaka, Japan

Location

Clinical Site

Shizuoka, Shizuoka, Japan

Location

Clinical Site

Chūōku, Tokyo, Japan

Location

Clinical Site

Chūō, Yamanashi, Japan

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Naoya Yamazaki

  National Cancer Center Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 15, 2017
• Study Start: May 25, 2017
• Primary Completion: June 30, 2018
• Study Completion: December 14, 2018
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

JP (12)