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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Soft Tissue Sarcoma; Advanced Sarcoma; Metastatic Sarcoma
• Intervention / Treatment: Drug: YH001; Drug: Envafolimab; Drug: Doxorubicin

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WK; Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.	Drug: YH001; Anti-CTLA4 antibody; Drug: Envafolimab; Anti-PD-L1 antibody; Other Names: KN035
Experimental: P1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WK; Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.	Drug: YH001; Anti-CTLA4 antibody; Drug: Envafolimab; Anti-PD-L1 antibody; Other Names: KN035
Experimental: P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK; Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.	Drug: YH001; Anti-CTLA4 antibody; Drug: Envafolimab; Anti-PD-L1 antibody; Other Names: KN035; Drug: Doxorubicin; Anthracycline
Experimental: P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK; Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.	Drug: YH001; Anti-CTLA4 antibody; Drug: Envafolimab; Anti-PD-L1 antibody; Other Names: KN035; Drug: Doxorubicin; Anthracycline
Experimental: P2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WK; Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks	Drug: YH001; Anti-CTLA4 antibody; Drug: Envafolimab; Anti-PD-L1 antibody; Other Names: KN035
Experimental: P2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WK; Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks	Drug: YH001; Anti-CTLA4 antibody; Drug: Envafolimab; Anti-PD-L1 antibody; Other Names: KN035
Experimental: P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK; Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses	Drug: YH001; Anti-CTLA4 antibody; Drug: Envafolimab; Anti-PD-L1 antibody; Other Names: KN035; Drug: Doxorubicin; Anthracycline
Experimental: P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK; Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses	Drug: YH001; Anti-CTLA4 antibody; Drug: Envafolimab; Anti-PD-L1 antibody; Other Names: KN035; Drug: Doxorubicin; Anthracycline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: YH001 concentrations	Determine YH001 trough concentration when given with envafolimab with or without doxorubicin.	8 months
Phase 1: Envafolimab concentrations	Determine envafolimab trough concentration when given with YH001 with or without doxorubicin.	8 months
Phase 1: Determine the Rate of YH001 Immunogenicity	Evaluate the formation of YH001 anti-drug antibodies (ADA).	8 months
Phase 1: Determine the Rate of Envafolimab Immunogenicity	Evaluate the formation of envafolimab anti-drug antibodies (ADA).	8 months
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
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
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
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
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
Phase 2: YH001 concentration	Determine YH001 trough concentration when given with envafolimab with or without doxorubicin.	22 months
Phase 2: Envafolimab concentration	Determine envafolimab trough concentration when given with YH001 with or without doxorubicin.	22 months
Phase 2: Determine the Rate of YH001 Immunogenicity	Evaluate the formation of YH001 anti-drug antibodies (ADA).	22 months
Phase 2: Determine the Rate of Envafolimab Immunogenicity	Evaluate the formation of envafolimab anti-drug antibodies (ADA).	22 months
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

Collaborators and Investigators

• Sponsor: Tracon Pharmaceuticals Inc.
• Investigators: Study Director: James Freddo, MD, Medical Monitor

Publications and helpful links

Helpful Links

• TRACON Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2022
• Primary Completion (Estimated): November 1, 2023
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: July 3, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: chondrosarcoma; PD-L1; CTLA-4; Tracon; STS; LMS; DDLS; ASPS; envafolimab; YH001
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: YH001/KN035SAR101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No