YH001 Plus Envafolimab With or Without Doxorubicin in Patients With Advanced or Metastatic Sarcoma

Soft Tissue Sarcoma Clinical Trial

Official title:

A Phase 1/2 Study of YH001 in Combination With Envafolimab With or Without Doxorubicin in Patients With Advanced or Metastatic Sarcoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05448820
• Other study ID #: YH001/KN035SAR101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 14, 2022
• Est. completion date: September 2025

Study information

• Verified date: September 2023
• Source: Tracon Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, open label, Phase 1/2 study of YH001 initially given in combination with envafolimab, and then given in combination with envafolimab plus doxorubicin in patients with advanced or metastatic sarcoma, followed by Phase 2 cohorts of patients with select histologies of advanced or metastatic sarcoma.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: September 2025
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed advanced or metastatic sarcoma patients without UPS or MFS who are refractory to or intolerant to standard treatments for their disease.

2. Histologically confirmed advanced or metastatic sarcoma patients without UPS or MFS who have not received any immune checkpoint inhibitors or doxorubicin, and with histology for which doxorubicin is considered a reasonable treatment option (for Cohort 1B, 2B and Expanded Cohort 1B and/or 2B)

3. Measurable disease by RECIST 1.1

4. Age = 18 years

5. Adequate organ function

6. Left ventricular ejection fraction (LVEF) as measured by echo or multigated acquisition scan of > 50% (for patients to receive doxorubicin)

7. Willingness and ability to consent for self to participate in study

8. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

9. Men who are sterile or agree to use a condom with spermicide .

10. Women of non-child bearing potential due to surgical sterilization or medically-documented ovarian failure confirmed by medical history, or women of child bearing potential who test negative for pregnancy at time of enrollment and agree to use at least 2 acceptable methods of birth control

Exclusion Criteria:

1. Gastrointestinal stromal tumor (GIST) or desmoid tumors

2. Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to enrollment

3. Known allergy to any component of any study drug that the patient would receive if enrolled into this study

4. Prior T-cell or NK-cell therapy

5. Prior pericardial or mediastinal radiation (for patients to receive doxorubicin)

6. Acute coronary syndromes within 6 months of enrollment

7. Women who are pregnant or breast feeding

8. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study

Related Conditions & MeSH terms

• Advanced Sarcoma
• Metastatic Sarcoma
• Sarcoma
• Soft Tissue Sarcoma

Intervention

Drug:
• YH001
Anti-CTLA4 antibody
• Envafolimab
Anti-PD-L1 antibody
• Doxorubicin
Anthracycline

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Duke University	Durham	North Carolina
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Sarcoma Oncology Center	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Tracon Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Determine recommended phase 2 dose of YH001 in combination with Envafolimab	Evaluate safety and tolerability and determine the recommended Phase 2 dose (RP2D) of YH001 when given with envafolimab dosed SC every 3 weeks in patients with advanced or metastatic sarcoma who are refractory to or intolerant to other available therapies.	8 months
Primary	Phase 1: Determine recommended phase 2 dose of YH001 in combination with Envafolimab with Doxorubicin	Evaluate safety and tolerability and determine RP2D of YH001 in combination with envafolimab dosed SC every 3 weeks and doxorubicin dosed every three weeks in patients with advanced or metastatic sarcoma who have not received doxorubicin and are refractory to or intolerant to other available therapies.	8 months
Primary	Phase 2: Determine the objective response rate (ORR) of YH001 in combination with Envafolimab and Doxorubicin	Determine the ORR of envafolimab, YH001 and doxorubicin by RECIST 1.1 by investigator assessment in patients who have not received immune checkpoint inhibitors or doxorubicin with subtypes of advanced or metastatic soft tissue sarcoma.	18 months
Primary	Phase 2: Determine the objective response rate (ORR) of YH001 in combination with Envafolimab	Determine the ORR of envafolimab and YH001 by RECIST 1.1 by investigator in patients with subtypes of advanced or metastatic soft tissue sarcoma who have not received immune checkpoint inhibitors.	22 months
Secondary	Phase 1: YH001 concentrations	Determine YH001 trough concentration when given with envafolimab with or without doxorubicin.	8 months
Secondary	Phase 1: Envafolimab concentrations	Determine envafolimab trough concentration when given with YH001 with or without doxorubicin.	8 months
Secondary	Phase 1: Determine the Rate of YH001 Immunogenicity	Evaluate the formation of YH001 anti-drug antibodies (ADA).	8 months
Secondary	Phase 1: Determine the Rate of Envafolimab Immunogenicity	Evaluate the formation of envafolimab anti-drug antibodies (ADA).	8 months
Secondary	Phase 1: Assessment of antitumor activity	Assess objective response rate (ORR) of YH001 by investigator using RECIST 1.1 when combined with envafolimab or envafolimab/doxorubicin combination in patients with advanced or metastatic sarcoma.	8 months
Secondary	Phase 2: Determine the disease control rate (DCR)	Determine the Disease Control Rate of envafolimab, YH001 and doxorubicin or envafolimab and YH001 in patients with advanced or metastatic sarcoma.	22 months
Secondary	Phase 2: Determine duration of response (DOR)	Determine the Duration of Response of envafolimab, YH001 and doxorubicin or envafolimab and YH001 in patients with advanced or metastatic sarcoma.	22 months
Secondary	Phase 2: Determine Progression Free Survival (PFS)	Determine Progression Free Survival of envafolimab, YH001 and doxorubicin or envafolimab and YH001 in patients with advanced or metastatic sarcoma.	22 months
Secondary	Phase 2: Determine Overall Survival (OS)	Determine Overall Survival of envafolimab, YH001 and doxorubicin or envafolimab and YH001 in patients with advanced or metastatic sarcoma.	22 months
Secondary	Phase 2: YH001 concentration	Determine YH001 trough concentration when given with envafolimab with or without doxorubicin.	22 months
Secondary	Phase 2: Envafolimab concentration	Determine envafolimab trough concentration when given with YH001 with or without doxorubicin.	22 months
Secondary	Phase 2: Determine the Rate of YH001 Immunogenicity	Evaluate the formation of YH001 anti-drug antibodies (ADA).	22 months
Secondary	Phase 2: Determine the Rate of Envafolimab Immunogenicity	Evaluate the formation of envafolimab anti-drug antibodies (ADA).	22 months
Secondary	Phase 2: Type Incidence and Severity of Adverse Events	Type, incidence, severity (graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0), timing, seriousness, and relatedness of AEs and laboratory abnormalities.	25 months

External Links

•   TRACON Pharmaceuticals