A Randomized, Controlled, Multi-center, Phase III Clinical Study to Investigate Recombinant Humanized PD-1 Monoclonal Antibody Injection (JS001) Versus Dacarbazine as the 1st-line Therapy for Unresectable or Metastatic Melanoma

NCT03430297 | Completed Phase 3 DMC

• 1 other identifier: HMO-JS001-III-MM-01
• Study Type: interventional
• Target: 256
• Locations: 1 country
• Sites: 11

Brief Summary

This is one phase III, randomized, open-label study in comparison of JS001 with dacarbazine as the 1st-line therapy for adult (≥18 years) subjects with unresectable or metastatic melanoma. The subjects will be 1:1 randomized and stratified in accordance with acral lentiginous melanoma and M stage (M0vsM1a/M1bvsM1c). Using standard dose and dose interval, the subjects will be given JS001 240mg intravenously, once every two weeks, or dacarbazine 1000mg/m2, d1, intravenously, once every three weeks. One cycle of therapy is 6 weeks (3 doses of JS001 or 2 doses of dacarbazine per cycle).

Conditions

Metastatic Melanoma; Unresectable Melanoma

Keywords

anti-PD-1 monoclonal antibody; the First Line Therapy; Dacarbazine; Melanoma

Outcome Measures

Primary Outcomes (1)

• the progression-free survival (PFS)

  To compare the progression-free survival (PFS) evaluated by one independent review board of radiological data in systemic treatment-naïve patients with unresectable, locally advanced or metastatic melanoma who are treated with JS001 versus dacarbazine.

  3 months

Secondary Outcomes (3)

• objective response rate (ORR)

  2 years

• duration of response (DOR)

  2 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  2 years

Study Arms (2)

JS001 240mg Q2W

EXPERIMENTAL

Biological: JS001 240mg Q2W

Dacarbazine 1000mg/m2 Q3W

ACTIVE COMPARATOR

Drug: Dacarbazine 1000mg/m2 Q3W

Interventions

JS001 240mg Q2W BIOLOGICAL

recombinant humanized anti-PD-1 monoclonal antibody injection (JS001) will be provided by the sponsor. Strength: 240mg/6ml/vial. 240mg, once every two weeks. Control drug: dacarbazine (1000mg/m2, d1, intravenously, once every three weeks). The dose will be given intravenously over 180 minutes (the infusion time can be prolonged according to the institutional criteria), starting from Week 1, once every 3 weeks, until progression of disease.

JS001 240mg Q2W

Dacarbazine 1000mg/m2 Q3W DRUG

The dose of DTIC will be calculated according to the following formula, where the 'X' represents the total mg dose of DTIC: X (mg) = \[body surface area (BSA) x (1000mg/m2)\]. The body surface area (BSA) is defined by Dubois formula: BSA (m2) = 0.007184\* (cm0.725) \* (kg0.425)

Dacarbazine 1000mg/m2 Q3W

Eligibility Criteria

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

You may qualify if:

• Patients are eligible for participation in the trial only when they meet the following criteria:
• Age ≥18 years, male or female;
• Systemic treatment-naïve, histologically confirmed unresectable stage III or IV melanoma. Previous adjuvant or neoadjuvant therapy is allowed, however, it is required to be completed at least three weeks prior to the randomization, and all the relevant adverse events have been recovered to normal or CTC-AE grade 1;
• Measurable lesion (according to RECIST v1.1 criteria);
• ECOG score 0 or 1
• Tumor tissue has to be provided (FFPE archival or newly acquired tissue block or unstained slide from FFPE) for analysis of biomarkers;
• Previous radiotherapy must be completed at least two weeks prior to administration of investigational product;
• The laboratory data for screening must meet the following criteria and should be acquired within 14 days prior to the first dose:
• Peripheral hemogram: white blood cell (WBC) ≥3.0×109/L, neutrophil (ANC) ≥1.5×109/L, platelet (PLT) ≥100×109/L, hemoglobin (Hgb) ≥90g/L;
• Renal function: serum creatinine°≤1.5 x ULN or calculated creatinine clearance (CrCl) \>40 mL/min (using Cockcroft Gault formula);
• Hepatic function: AST/ALT≤2.5 x ULN in subjects without hepatic metastasis, AST/ALT≤5 x ULN in those with hepatic metastasis;
• Total bilirubin ≤1.5 x ULN (except the subjects with Gilbert syndrome, the total bilirubin must be \< 3.0mg/dL).
• Estimated survival ≥16 weeks;
• Men with reproductive capacity or women of childbearing potential must use highly effective contraceptive methods during the trial (e.g., oral contraceptives, intrauterine device, sexual abstinence or barrier method combined with spermicide), and continue contraception for 12 months after the end of treatment;
• Subject is willing to participate in the study, sign the informed consent form with good compliance and cooperation with follow-up;

You may not qualify if:

• Patients will be excluded from the trial when they have any one of the following conditions:
• Previous treatment with anti-PD-1, anti-PD-L1or anti-PD-L2 therapy;
• Known allergy to recombinant humanized anti-PD-1 monoclonal antibody and its components;
• Presence of BRAF mutation, except unwillingness or inability to receive BRAF mutation inhibitor;
• Malignant melanoma originated from eyes or mucosa;
• Having received other anti-tumor therapy (including corticosteroids, immunotherapy) or participated in other clinical studies within 4 weeks prior to the start of treatment, or having not recovered from the previous toxicity (except grade 2 alopecia and grade 1 neurotoxicity);
• Pregnant or lactating women;
• HIV positive; HCV positive; positive HBV DNA copies detected simultaneously with HBsAg or HBCAb positive (quantitative detection limit 500 IU/ml);
• History of active pulmonary tuberculosis;
• Active autoimmune disease requiring systemic treatment in the past two years (e.g., use of disease-modulating drugs, corticosteroids or immunosuppressive drugs), relevant alternative therapy is allowed (e.g., thyroxine, insulin or physiological corticosteroid replacement therapy for renal or pituitary insufficiency);
• Other serious, uncontrollable concomitant diseases that may affect the compliance with protocol or interfere with interpretation of the results, including active opportunistic infection (serious) infection in progressive stage, uncontrollable diabetes, cardiovascular disease (grade Ⅲ or Ⅳ heart failure defined by New York Heart Association, degree Ⅱ and above cardiac block, myocardial infarction in the past 6 months, unstable arrhythmia or unstable angina pectoris, cerebral infarction within 3 months, etc.) or pulmonary disease (history of interstitial pneumonia, obstructive pulmonary disease and symptomatic bronchospasm);
• Subjects with active central nervous system (CNS) metastasis, active brain metastasis or leptomeningeal metastatic foci. For the subjects with brain metastasis, if they have received treatment and have no evidence of progressive disease on the nuclear magnetic resonance imaging (MRI) at least 8 weeks after completion of the treatment and within 28 days prior to the first dose, they are eligible to participate in the study. Meanwhile, it is required corticosteroid for systemic therapy at the dose of immunosuppressant (\>10mg/day prednisone equivalent) must not be needed at least two weeks prior to administration of investigational product;
• Previously receiving hematopoietic stimulating factor within two weeks prior to the start of treatment, for example, colony stimulating factor, erythropoietin;
• Having been injected by live vaccine within 4 weeks prior to the start of treatment;
• Major surgery within 4 weeks prior to the start of treatment (not including diagnostic surgery);

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (11)

Hefei Binhu Hospital

Hefei, Anhui, 230092, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

Location

Wuhan Union Hospital

Wuhan, Hubei, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

Location

The First Hospital Of Jilin University

Changchun, Jilin, 130061, China

Location

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

Location

Yunnan Cancer Hospital

Kunming, Yunnan, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310005, China

Location

Related Publications (1)

• Sheng X, Huang G, Fang M, Li K, Wu D, Zhang X, Chen J, Zhu D, Chen Y, Li H, Gao Q, Wu L, Tang B, Yan X, Zeng R, Li J, Yu W, Xu J, Hao Y, Jin C, Zou J, Guo J. Toripalimab vs Dacarbazine as First-Line Therapy for Advanced Melanoma of Acral Subtype: The Phase 3 MELATORCH Randomized Clinical Trial. JAMA Oncol. 2026 Jan 2:e255751. doi: 10.1001/jamaoncol.2025.5751. Online ahead of print.

  PMID: 41481311 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Dacarbazine

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)

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

Study Officials

• Jun Guo

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: February 12, 2018
• Study Start: February 2, 2018
• Primary Completion: July 12, 2023
• Study Completion: November 27, 2023
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (11)