A Study of HX008 Plus Transcatheter Arterial Chemoembolization (TACE) in the First-Line Treatment of Subjects With Stage IV (M1c) Melanoma That is Metastatic to the Liver

NCT05647954 | Unknown Phase 3

• 1 other identifier: HX008-Ⅲ-MM-01
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to compare the clinical benefit, as measured by Progression-Free Survival (PFS) and Overall Survival(OS), achieved by HX008 Plus Transcatheter Arterial Chemoembolization (TACE) or Temozolomide Plus Transcatheter Arterial Chemoembolization (TACE) in the First-Line Treatment of Subjects With Stage IV (M1c) Melanoma That is Metastatic to the Liver.

Conditions

Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) by Independent Review Committee(IRC)

  PFS, defined as the time from randomization to the first documented disease.(HX008 + TACE vs Temozolomide + TACE)

  2 years

• Overall Survival (OS)

  OS, defined as the duration from the start of treatment to death of any cause.(HX008 + TACE vs Temozolomide + TACE)

  2 years

Secondary Outcomes (7)

• Progression-free Survival (PFS) by Investigators

  2 years

• Objective Response Rate (ORR)

  2 years

• Disease Control Rate (DCR)

  2 years

• Duration of Response (DOR)

  2 years

• Progression-free Survival (PFS) by IRC or investigators

  2 years

Study Arms (3)

HX008 Plus Transcatheter Arterial Chemoembolization(TACE)

EXPERIMENTAL

Drug: HX008 + TACE

Temozolomide Plus Transcatheter Arterial Chemoembolization (TACE)

ACTIVE COMPARATOR

Drug: Temozolomide + TACE

Pembrolizumab

ACTIVE COMPARATOR

Drug: Pembrolizumab

Interventions

HX008 + TACE DRUG

HX008 Subjects receive HX008 200 mg intravenous (IV) ,day1,every 3 weeks (Q3W) Procedure: TACE cisplatin 75 mg/sqm, day1, every 6 weeks; fotemustine 100 mg/sqm, day2, every 6 weeks; lipiodol is usually 5-10 ml (According to the location and number of lesions).

HX008 Plus Transcatheter Arterial Chemoembolization(TACE)

Temozolomide + TACE DRUG

Temozolomide Subjects receive Temozolomide 200 mg/sqm intravenous (IV),day1-5, every 3 weeks (Q3W) Procedure: TACE : cisplatin 75 mg/sqm, day1, every 6 weeks; fotemustine 100 mg/sqm, day2, every 6 weeks; lipiodol is usually 5-10 ml (According to the location and number of lesions).

Temozolomide Plus Transcatheter Arterial Chemoembolization (TACE)

Pembrolizumab DRUG

Subjects receive Pembrolizumab 2 mg/kg intravenous (IV),day1, every 3 weeks (Q3W)

Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign the Informed Consent Form（ICF）, understand the study, be willing to follow and be able to complete all test procedures;
• Males or females, aged 18 to 75 are eligible on the day of signing the informed consent form;
• Subjects with stage IV (M1c) melanoma confirmed by histology with liver metastasis approved by Pathology;
• No prior systemic treatment for Stage IV (M1c) Melanoma with liver Metastatic; except:
• Melanoma with BRAF V600 mutation-positive may receive targeted therapy(e.g., BRAF/MEK inhibitor, alone or in combination) as first-line treatment for advanced or metastatic disease;
• Prior targeted therapy or immunotherapy (e.g., anti-PD-1 monoclonal antibody, anti-CTLA-4 monoclonal antibody or interferon, BRAF/MEK inhibitors, alone or in combination) as adjuvant or neoadjuvant therapy, if no recurrence or metastasis occurred during treatment or within 6 months of treatment termination. Prior adjuvant temozolomide and cisplatin chemotherapy of primary mucosa melanoma, without recurrence or metastasis during treatment or within 6 months of treatment termination.
• Subjects must have a BRAF-V600 mutation or agree to carry out BRAF-V600 mutation detection during the screening phase ;
• At least one measurable lesion of the subject's liver according to RECIST version 1.1 (Lesions with the longest diameter ≥ 10mm)
• Target lesion has not received prior local treatment, including transarterial embolization (TAE), TACE, transarterial radioembolization (TARE), surgery, radiofrequency ablation (RFA), microwave ablation (MWA), other thermal ablation, percutaneous ethanol injection (PEI), radiation therapy, etc. Subjects who have received prior local treatment for non-target lesions are eligible for the study. Local treatment must be completed at least 4 weeks before randomization.
• Liver function classified as Child-Pugh class A or B with a score ≤ 7, and no history of hepatic encephalopathy；
• Suitability for the TACE procedures and chemotherapeutic agents pre-specified by the research center, without any contraindications;
• Eastern Cooperative Oncology Group (ECOG) of 0 or 1;
• Estimated life expectancy of ≥12 weeks;
• Has sufficient organ and bone marrow function((no blood transfusions allowed for 14 days prior to blood routine, no any cell growth factors or/and platelet-raising drugs) to meet the following laboratory examination standards:
• Absolute neutrophil count (NUT#)≥1.5×10\^9/L

You may not qualify if:

• Malignant melanoma of ocular origin;
• Investigator-identified contraindications to TACE (e.g., portal vein obstruction without formation of collateral vessels, etc.);
• Liver lesions ≥ 10 cm in any dimension, more than 10 lesions on imaging evaluation, or liver lesions representing ≥ 50% of the liver volume.
• Subjects diagnosed with any other malignancy within 3 years before randomization, except for malignancies with a low risk of metastasis and death (5-year survival rate \> 90%), such as adequately basal cell or squamous cell skin cancer or carcinoma in situ of the cervix and other carcinomas in situ;
• Had active autoimmune disease (except for psoriasis), that has required systemic treatment in the past 2 years((e.g., corticosteroids or immunosuppressive drugs). Except for alternative therapies (eg, thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency);
• Need to receive systemic corticosteroids (dose equivalent to \> 10 mg prednisone/day) or other immunosuppressive drugs within 14 days before enrollment or during the study period. Those under the following conditions are eligible:
• Locally external use or inhaled corticosteroids;
• short-term (≤7 days) use of glucocorticoids for the prevention or treatment of nonautoimmune allergic diseases;
• Had received anti-tumor treatment within 4 weeks before randomization, or have not recovered from the toxicity of the last treatment (except for hair loss of Grade 2 and neurotoxicity of Grade 1);
• Had received radiotherapy within 2 weeks before randomization， or had prior radiation therapy, or who has not recovered (≤ Grade 1 or at Baseline) from AEs due to previous radiation therapy;
• Had received major surgery, open biopsy, or severe trauma within 4 weeks before randomization; Definition of major surgery: the minimum of 3 weeks of post-operative recovery time is required to undergo this study;
• Had severe infection within 4 weeks or active infection requiring IV infusion or oral administration of antibiotics within 2 weeks before randomization;
• Had participated in other drug or device clinical trials within 4 weeks before randomization;
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or found during the screening phase. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks, have no evidence of new or enlarging brain metastases, and also are off steroids 14 days before dosing with study medication may participate. Subjects with known untreated, asymptomatic brain metastases (ie, Lesions with numbers ≤ 3, and Lesions with the longest diameter ≤ 1 cm, ) may participate;
• Has pleural effusion, pericardial effusion, or uncontrolled ascites requiring repeated drainage (once a month or more);

Sponsors & Collaborators

• Taizhou Hanzhong biomedical co. LTD: lead

Study Sites (1)

Beijing Cancer hospital

Beijing, Beijing Municipality, 100142, China

Location

MeSH Terms

Interventions

Temozolomide; pembrolizumab

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jun Guo, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Guo, MD

CONTACT

861088196348; guoj307@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2022
• First Posted: December 13, 2022
• Study Start: December 31, 2022
• Primary Completion: December 30, 2024
• Study Completion: June 30, 2025
• Last Updated: December 13, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)