YH001 Plus Envafolimab With or Without Doxorubicin in Patients With Advanced or Metastatic Sarcoma
- Conditions
- Soft Tissue SarcomaMetastatic SarcomaAdvanced Sarcoma
- Interventions
- Registration Number
- NCT05448820
- Lead Sponsor
- Tracon Pharmaceuticals Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 15
- Histologically confirmed advanced or metastatic sarcoma patients without UPS or MFS who are refractory to or intolerant to standard treatments for their disease.
- 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)
- Measurable disease by RECIST 1.1
- Age ≥ 18 years
- Adequate organ function
- Left ventricular ejection fraction (LVEF) as measured by echo or multigated acquisition scan of > 50% (for patients to receive doxorubicin)
- Willingness and ability to consent for self to participate in study
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- Men who are sterile or agree to use a condom with spermicide .
- 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
- Gastrointestinal stromal tumor (GIST) or desmoid tumors
- Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days prior to enrollment
- Known allergy to any component of any study drug that the patient would receive if enrolled into this study
- Prior T-cell or NK-cell therapy
- Prior pericardial or mediastinal radiation (for patients to receive doxorubicin)
- Acute coronary syndromes within 6 months of enrollment
- Women who are pregnant or breast feeding
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WK YH001 Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks. P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Doxorubicin Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks. P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK YH001 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 P1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WK YH001 Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks. P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK YH001 Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks. P2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WK YH001 Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK YH001 Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks. P2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WK YH001 Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK YH001 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 P1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WK Envafolimab Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks. P2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WK Envafolimab Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WK Envafolimab Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks. P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Envafolimab Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks. P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Envafolimab Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks. P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Doxorubicin Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks. P2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WK Envafolimab Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Envafolimab 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 P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Doxorubicin 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 P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Envafolimab 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 P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Doxorubicin 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
- Primary Outcome Measures
Name Time Method Phase 1: Determine recommended phase 2 dose of YH001 in combination with Envafolimab 8 months 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.
Phase 1: Determine recommended phase 2 dose of YH001 in combination with Envafolimab with Doxorubicin 8 months 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.
Phase 2: Determine the objective response rate (ORR) of YH001 in combination with Envafolimab and Doxorubicin 18 months 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.
Phase 2: Determine the objective response rate (ORR) of YH001 in combination with Envafolimab 22 months 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.
- Secondary Outcome Measures
Name Time Method Phase 2: Determine the Rate of YH001 Immunogenicity 22 months Evaluate the formation of YH001 anti-drug antibodies (ADA).
Phase 2: Determine the Rate of Envafolimab Immunogenicity 22 months Evaluate the formation of envafolimab anti-drug antibodies (ADA).
Phase 1: YH001 concentrations 8 months Determine YH001 trough concentration when given with envafolimab with or without doxorubicin.
Phase 1: Envafolimab concentrations 8 months Determine envafolimab trough concentration when given with YH001 with or without doxorubicin.
Phase 1: Determine the Rate of YH001 Immunogenicity 8 months Evaluate the formation of YH001 anti-drug antibodies (ADA).
Phase 1: Determine the Rate of Envafolimab Immunogenicity 8 months Evaluate the formation of envafolimab anti-drug antibodies (ADA).
Phase 2: Determine the disease control rate (DCR) 22 months Determine the Disease Control Rate of envafolimab, YH001 and doxorubicin or envafolimab and YH001 in patients with advanced or metastatic sarcoma.
Phase 1: Assessment of antitumor activity 8 months 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.
Phase 2: Determine Progression Free Survival (PFS) 22 months Determine Progression Free Survival of envafolimab, YH001 and doxorubicin or envafolimab and YH001 in patients with advanced or metastatic sarcoma.
Phase 2: Envafolimab concentration 22 months Determine envafolimab trough concentration when given with YH001 with or without doxorubicin.
Phase 2: Type Incidence and Severity of Adverse Events 25 months 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.
Phase 2: Determine duration of response (DOR) 22 months Determine the Duration of Response of envafolimab, YH001 and doxorubicin or envafolimab and YH001 in patients with advanced or metastatic sarcoma.
Phase 2: Determine Overall Survival (OS) 22 months Determine Overall Survival of envafolimab, YH001 and doxorubicin or envafolimab and YH001 in patients with advanced or metastatic sarcoma.
Phase 2: YH001 concentration 22 months Determine YH001 trough concentration when given with envafolimab with or without doxorubicin.
Trial Locations
- Locations (6)
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Duke University
🇺🇸Durham, North Carolina, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Northwestern University
🇺🇸Chicago, Illinois, United States