A Study of LVGN6051 Combined with Anlotinib in Patient with Soft Tissue Sarcoma

NCT05301764 | Recruiting Phase 1

• 1 other identifier: LVGN6051-301
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to asess the safety and tolerability and efficacy of LVGN6051 combined with anlotinib in patient with soft tissue sarcoma.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (3)

• To characterize the safety and tolerability of LVGN6051 combined with Anlotinib and to recommend the Phase II dose

  To evaluate the safety and tolerability of LVGN6051 combined with Anlotinib through evaluation of the frequency and severity of AEs, serious adverse events(SAEs)

  Up to 24 months

• To characterize the safety and tolerability of LVGN6051 combined with Anlotinib and to recommend the Phase II dose

  To evaluate the safety and tolerability of LVGN6051 combined with Anlotinib through evaluation of the type of dose-limiting toxicities (DLTs)

  At the end of Cycle 1 (each cycle is 21 days)

• to determine objective response rate (ORR) of phase II

  To assess the preliminary efficacy of LVGN6051 combined with Anlotinib in terms of objective response rate (ORR).

  Up to 24 months

Secondary Outcomes (13)

• To characterize the safety and tolerability of LVGN6051 combined with Anlotinib

  Up to 24 months

• To assess preliminary efficacy on overall survival (OS)(for Phase II only) using LVGN6051 combined with Anlotinib

  Up to 24 months

• To assess preliminary efficacy on progression-free survival (PFS) using LVGN6051 combined with Anlotinib

  Up to 24 months

• To assess preliminary efficacy on duration of response (DoR) using LVGN6051 combined with Anlotinib

  Up to 24 months

• To assess preliminary efficacy on disease control rate (DCR) using LVGN6051 combined with Anlotinib

  Up to 24 months

Study Arms (1)

LVGN6051 combined with Anlotinib

EXPERIMENTAL

LVGN6051 Dose Escalation in the combination treatment with Anlotinib

Combination Product: LVGN6051 and Anlotinib

Interventions

LVGN6051 and Anlotinib COMBINATION_PRODUCT

LVGN6051: Route of administration is IV infusion, and the frequency of administration is once every 3 weeks(Q3W). One cycle is 3 weeks, and treatment can be up to 35 cycles if patients receive benefits. Anlotinib: Rout of administration is oral. The initial dose of anlotinib was 12 mg for subjects with body surface area ≥ 1.5m2 and 10 mg for subjects with body surface area \< 1.5m2. If the subjects in the combined treatment group were not tolerated, the dose of anlotinib was reduced to 10 mg for subjects with body surface area ≥ 1.5m2 and 8 mg for subjects with body surface area \< 1.5m2. One cycle is 3 weeks, including oral for 2 weeks and withdrawal for 1 week.

LVGN6051 combined with Anlotinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged ≥ 18 years, who was histologically or cytologically diagnosed unresectable locally advanced, metastatic or recurrent refractory soft tissue sarcoma.
• Ability to understand and willingness to sign a written informed consent document (ICF). Informed consent of subjects must be performed before the study, and the written informed consent shall be voluntarily signed by himself or his guardian; The subject or his guardian can communicate well with the investigator, and perform according to the protocol.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Estimated life expectancy, in the judgment of the Investigator, of at least 90 days.
• Adequate bone marrow function, as defined by all of the following:
• hemoglobin (Hb) ≥ 90 g/L, and
• absolute neutrophil count (ANC) ≥ 1.5x109/L, and
• platelet count (PLT) ≥ 75x109/L.
• Adequate liver function, as defined by all of the following:
• Total bilirubin ≤ 1.5 × ULN; or ≤ 2.5 × ULN for patients who have serum bilirubin increases due to underlying Gilbert's Syndrome or familial benign unconjugated hyperbilirubinemia.
• Aspartate Aminotransferase (AST) ≤ 1.5 × ULN, and Alanine Transaminase (ALT) ≤ 1.5× ULN.
• International normalized ratio (INR) or prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤ 1.5×ULN, for subjects who are receiving anticoagulant therapy, INR level should be within therapeutic range.
• Amylase and lipase ≤1.5 × ULN
• Adequate renal function as defined by an estimated serum creatinine clearance of ≥ 50 mL/min (calculated by Cockcroft-Gault formula) or serum creatinine≤1.5×ULN.
• Women of childbearing potential must agree to abstain from heterosexual intercourse or use highly effective contraceptive methods from the time of signing informed consent and through 120 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she (or her partner) is participating in this study, she should inform her research physician immediately.

You may not qualify if:

• Prior therapy with anti-CD137 therapy.
• Receipt of systemic anticancer therapy including investigational agents or devices within 5 half-lives of the first dose of study treatment. For anticancer therapies with half-life greater than 5 days, a washout of 28 days or longer is acceptable
• The subject was experienced radiotherapy within 14 days before the first dose of study treatment. \[Previous radiotherapy to the central nervous system (CNS) within 28 days of the first dose of study treatment\].
• Known unstable CNS metastasis and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically and radiographically stable, without evidence of recurrence/progression, have no evidence of new or enlarging brain metastases or cephaledema, and are using no corticosteroids for at least 7 days prior to study medication.
• Received a live-virus vaccine within 30 days of the first dose of study drug.
• Grade ≥ 3 allergic reaction to treatment with a monoclonal antibody or has a known or suspected hypersensitivity to components of the study treatment(s).
• Baseline QT interval corrected by Fridericia's formula (QTcF) \> 480 milliseconds or known to have congenital prolonged QT syndrome.
• History of Grade ≥ 3 immune-related AEs (irAEs). Exceptions: hypothyroidism, type 1 diabetes mellitus (Type 1 DM), and dermatologic irAEs (patients with previous Steven Johnson Syndrome, toxic epidermal necrolysis or other severe forms of dermatitis are ineligible) are allowed. Type 1 DM should be controlled with HbA1c \<8% as per ADA recommendation.
• Receiving an immunologically based treatment for any reason, including chronic use of systemic steroids equivalent to \> 10 mg/day of prednisone within 7 days of the first dose of study drug or at any time during study participation.
• Note: Use of inhaled or topical steroids or systemic corticosteroids equivalent to ≤ 10 mg/day prednisone equivalent is permitted as is short-term use of corticosteroids at doses equivalent to \> 10 mg/day of prednisone (e.g., pre-medication prior to contrast).
• Treatment with systemic immune-stimulatory agents (e.g., IL-2, IFNγ) within 4 weeks prior to the first dose of study drug.
• History or current active or chronic autoimmune disease including but not limited to inflammatory bowel disease, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis that has required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease.
• Exception: Patients with vitiligo or resolved childhood asthma/atopy, hypothyroidism on stable hormone replacement, controlled asthma, Type I diabetes, Graves' disease, Hashimoto's disease, or with Medical Monitor approval.
• Clinically significant cardiac condition, including unstable angina, acute myocardial infarction within 6 months of Cycle 1 Day 1, New York Heart Association Class III or IV congestive heart failure, unstable angina pectoris or arrhythmia requiring therapy.
• Note: A patient with an arrhythmia may enroll if the patient is on antiarrhythmic medication and is in a rate- controlled rhythm on the screening electrocardiogram (ECG).

Sponsors & Collaborators

• Lyvgen Biopharma Holdings Limited: lead

Study Sites (5)

Henan cancer hospital

Zhenzhou, Henan, 450008, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

NOT YET RECRUITING

Shanghai Sixth People's Hospital

Shanghai, Shanghai Municipality, 200233, China

NOT YET RECRUITING

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310052, China

NOT YET RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

anlotinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Haiyan Hu

  Shanghai 6th People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Yang

CONTACT

+8618616176786; yan.yang@lyvgen.com

Study Design

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

Study Record Dates

• First Submitted: March 2, 2022
• First Posted: March 31, 2022
• Study Start: May 25, 2022
• Primary Completion: March 19, 2025
• Study Completion: October 19, 2025
• Last Updated: October 15, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)