Interferon-α1b Combined With Toripalimab and Anlotinib Hydrochloride in Advanced Unresectable Melanoma

NCT05539118 | Not Yet Recruiting Phase 1

• 1 other identifier: KY20222092-C-1
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of recombinant human interferon-α1b (IFN-α1b) combined with toripalimab and anlotinib hydrochloride in patients with unresectable advanced melanoma. This study consists of 2 phases（ Ib / II）. Phase Ib will determine the recommended phase Ⅱ dose for anlotinib hydrochloride. Phase II will evaluate the efficacy and safety of the triple combination regimens.

Conditions

Melanoma

Keywords

Melanoma; unresectable; Interferon-alfa1b; Toripalimab; Anlotinib

Outcome Measures

Primary Outcomes (3)

• Phase I: Recommended phase II dose (RP2D) of anlotinib hydrochloride

  RP2D of anlotinib hydrochloride will be depended according to the dose-limiting toxicities of anlotinib hydrochloride

  12 weeks after first drug administration

• Phase II: Objective response rate (ORR)

  proportion of patients with a complete response or partial response to treatment

  Up to 24 months after the last episode

• Phase II: progression-free survival (PFS)

  time from enrollment to progression or death

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcomes (4)

• disease control rate (DCR)

  Up to 60 months after the last episode

• duration of response (DOR)

  Up to 60 months after the last episode

• overall survival(OS)

  From date of enrollment until the date of death from any cause, assessed up to 60 months

• Clinical Benefit Rate(CBR)

  Week 0-24

Study Arms (1)

Recombinant human interferon α1b + toripalimab + anlotinib hydrochloride

EXPERIMENTAL

Recombinant human interferon α1b administered 600μg every other day. Toripalimab administered 240mg intravenously every three weeks. Anlotinib hydrochloride given 12mg or 10mg or 8mg orally (Daily for two weeks continuously, followed by one week of rest). A recommended phase II dose (RP2D) of anlotinib hydrochloride will be determined.

Drug: Recombinant human interferon α1b; Drug: Toripalimab; Drug: Anlotinib hydrochloride

Interventions

Recombinant human interferon α1b DRUG

Recombinant human interferon α1b is a protein with potent antiviral, antiproliferative and immunomodulatory properties.

Recombinant human interferon α1b + toripalimab + anlotinib hydrochloride

Toripalimab DRUG

Toripalimab is a recombinant, humanized programmed death receptor (PD-1) monoclonal antibody that binds to PD- and prevents binding of PD-1 with programed death ligands 1 (PD-L1) and PD-L2. It can function to activate cytotoxic T lymphocytes and inhibit tumor growth.

Recombinant human interferon α1b + toripalimab + anlotinib hydrochloride

Anlotinib hydrochloride DRUG

Anlotinib hydrochloride is a novel oral tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR) and c-kit.

Recombinant human interferon α1b + toripalimab + anlotinib hydrochloride

Eligibility Criteria

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

You may qualify if:

• Aged 18-75.
• ECOG performance status of 0 or 1
• Life expectancy ≥ 3 months;
• Histologically or cytologically confirmed diagnosis of unresectable stage IIIc, IIId and IV melanoma by the American Joint Committee on Cancer (AJCC) (the 8th Edition). (Note: uveal melanoma cases are excluded)
• Baseline tumor specimens available for NGS analysis or equivalent test results acceptable by the principal investigator.
• Measurable disease by RECIST v1.1 criteria
• Adequate organ and marrow function (within 4 weeks prior to study treatment initiation):
• A negative urine or plasma β-HCG test result is required at screening for female patients of childbearing potential.
• Contraception is required for patients and their partners throughout the trial and within 1 year after the last dose of study treatment.
• Capable of understanding and complying with the study protocol requirements ( including follow-up visit and examinations).
• Be willing to signed a written informed consent document before enrollment.

You may not qualify if:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to recombinant human interferon-α1bcombined, toripalimab and anlotinib hydrochloride.
• Patients accepted other anti-tumor clinical trials within 4 weeks prior to study entry.
• Patients accepted anti-tumor radiotherapy within 4 weeks prior to study entry.
• Disease improved by in response to anti-tumor therapies within 4 weeks including perioperative chemotherapy, molecularly targeted therapy, PD-1/PD-L1/CTLA-4 immune therapy, anti-angiogenesis therapy (such as sunitinib, sorafenib, regorafenib, bevacizumab, imatinib, apatinib) or interferon, herbal supplements.
• Plan to take other systemic or local anti-tumor therapy during the current study
• Systemic treatment with either corticosteroid (\> 10 mg /kg prednisone equivalents) or other immunosuppressive medications prior to 2 weeks prior to study dose initiation
• Known hematologic malignancy, primary brain tumor, sarcoma or any other primary solid tumor unless the disease-free period is over 5 years.
• Imaging confirmed of central nervous system (CNS) metastases with or without meningeal carcinomatosis
• Known severe hypersensitivity reaction of another mono-antibody therapy.
• Known active autoimmune disease requiring systemic treatment (such as corticosteroids or immunosuppressive medications) or related replacement therapies (such as thyroid hormone for hypothyroidism, insulin for diabetes or physiological glucocorticoid replacement therapy for adrenal or pituitary insufficiency) in the past 2 years.
• Individuals with bleeding tendency or under thrombolytic or anticoagulant therapy. Coagulation abnormalities as the following circumstances: INR \>1.5；PT \> 1.2 ULN；PTT \> 1.2 ULN.
• Use of anticoagulants or vitamin K antagonists such as warfarin, heparin or similar drugs
• Obvious hemoptysis or daily hemoptysis above 2.5ml in the past 2 months
• Any condition has potential risk of gastrointestinal bleeding or perforation, such as active gastrointestinal ulcer, known intra luminal metastases,inflammatory bowel disease; known abdominal fistula, gastrointestinal perforation or intraperitoneal abscess 4 weeks prior to entry of the study entry
• Open wounds, ulcers or fractures

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (1)

Air Force Military Medical University/ Fourth Military Medical University

Xi'an, Shaanxi, 710032, China

Location

MeSH Terms

Conditions

Melanoma

Interventions

toripalimab

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

Study Officials

• Guannan Zhu, M.D.;Ph.D

  Xijing Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guannan Zhu, M.D.;Ph.D

CONTACT

0086-84775406-8403; to_rain77@163.com

Study Design

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

Study Record Dates

• First Submitted: August 17, 2022
• First Posted: September 14, 2022
• Study Start: September 30, 2022
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 14, 2022

Record last verified: 2022-08

Locations

CN (1)