Clinical trial NCT03153085: A Study of Combination with TBI-1401(HF10) and Ipilimumab in Japanese Patients with Unresectable or Metastatic Melanoma
Official title: A Phase II Study of Combination Treatment with TBI-1401(HF10), a Replication-competent HSV-1 Oncolytic Virus, and Ipilimumab in Japanese Patients with Stage IIIB, IIIC, or IV Unresectable or Metastatic Malignant Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Takara Bio Inc.
Sponsor class: INDUSTRY
First posted: 2017-05-15
Enrollment: 28
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: The study is designed to assess efficacy and safety with repeated administration of intratumoral injections of TBI-1401(HF10) at 1x10\^7 TCID50/mL in combination with intravenous infusions of 3mg/kg ipilimumab in Japanese patients.

This is a single arm, open label Phase II study, to evaluate the efficacy and safety of TBI-1401(HF10) treatment in combination with the immunologic checkpoint inhibitor, ipilimumab (anti-CTLA-4 monoclonal antibody). The study population will include patients with Stage IIIB, IIIC or IV unresectable or metastatic malignant melanoma who are ipilimumab-eligible.

Patients will receive the dose of 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) + ipilimumab at 3 mg/kg (for a total of 4 intravenous infusions, each administered 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 they have tolerated the study treatment, are responding, have stable disease, or have progressive disease that is not clinically significant in the judgment of the Investigator.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Best overall response rate (BORR) by irRC
timeFrame: at 24 weeks
Secondary outcomes:
measure: Best overall response rate (BORR) by mWHO response criteria
timeFrame: at weeks 24
measure: Best overall response rate (BORR) by RECIST version 1.1
timeFrame: at weeks 24
measure: Objective response rate (ORR) by irRC
timeFrame: at weeks 6, 12, 18, and 24
measure: Objective response rate (ORR) by mWHO
timeFrame: at weeks 6, 12, 18, and 24
measure: Objective response rate (ORR) by RECIST version 1.1
timeFrame: at weeks 6, 12, 18, and 24
measure: Adverse event summaries, vital signs, and laboratory parameters to evaluate the safety and tolerability.
timeFrame: through study completion, up to 1 year
measure: Progression-free survival (PFS)
timeFrame: through disease progression, up to 3 years
measure: Durable response rate (DRR)
timeFrame: for 1 year
measure: 1 year survival rate
timeFrame: at 1 year
Other outcomes:
measure: Levels of antibody to HSV-1
timeFrame: up to weeks 24
measure: Change in immunologic parameters in serum
timeFrame: up to weeks 24
measure: Histopathological response with TBI-1401(HF10) administrated tumor
timeFrame: up to weeks 24
Locations:
city: Nagakute
country: Japan
facility: Clinical Site
state: Aichi
city: Nagoya
country: Japan
facility: Clinical Site
state: Aichi
city: Kurume
country: Japan
facility: Clinical Site
state: Fukuoka
city: Sapporo
country: Japan
facility: Clinical Site
state: Hokkaido
city: Tsukuba
country: Japan
facility: Clinical Site
state: Ibaraki
city: Chūōku
country: Japan
facility: Clinical Site
state: Tokyo
city: Chūō
country: Japan
facility: Clinical Site
state: Yamanashi
city: Fukuoka
country: Japan
facility: Clinical Site
city: Kumamoto
country: Japan
facility: Clinical Site
city: Niigata
country: Japan
facility: Clinical Site
city: Shizuoka
country: Japan
facility: Clinical Site
city: Ōsaka
country: Japan
facility: Clinical Site
Study officials:
affiliation: National Cancer Center Hospital
name: Naoya Yamazaki
role: PRINCIPAL_INVESTIGATOR
References: