Clinical trial NCT05448820: YH001 Plus Envafolimab With or Without Doxorubicin in Patients With Advanced or Metastatic Sarcoma
Official title: A Phase 1/2 Study of YH001 in Combination With Envafolimab With or Without Doxorubicin in Patients With Advanced or Metastatic Sarcoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Sarcoma
Metastatic Sarcoma
Soft Tissue Sarcoma
Keywords: Tracon
STS
LMS
DDLS
ASPS
envafolimab
YH001
CTLA-4
PD-L1
chondrosarcoma
Lead sponsor: Tracon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2022-07-07
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Determine recommended phase 2 dose of YH001 in combination with Envafolimab
timeFrame: 8 months
measure: Phase 1: Determine recommended phase 2 dose of YH001 in combination with Envafolimab with Doxorubicin
timeFrame: 8 months
measure: Phase 2: Determine the objective response rate (ORR) of YH001 in combination with Envafolimab and Doxorubicin
timeFrame: 18 months
measure: Phase 2: Determine the objective response rate (ORR) of YH001 in combination with Envafolimab
timeFrame: 22 months
Secondary outcomes:
measure: Phase 1: YH001 concentrations
timeFrame: 8 months
measure: Phase 1: Envafolimab concentrations
timeFrame: 8 months
measure: Phase 1: Determine the Rate of YH001 Immunogenicity
timeFrame: 8 months
measure: Phase 1: Determine the Rate of Envafolimab Immunogenicity
timeFrame: 8 months
measure: Phase 1: Assessment of antitumor activity
timeFrame: 8 months
measure: Phase 2: Determine the disease control rate (DCR)
timeFrame: 22 months
measure: Phase 2: Determine duration of response (DOR)
timeFrame: 22 months
measure: Phase 2: Determine Progression Free Survival (PFS)
timeFrame: 22 months
measure: Phase 2: Determine Overall Survival (OS)
timeFrame: 22 months
measure: Phase 2: YH001 concentration
timeFrame: 22 months
measure: Phase 2: Envafolimab concentration
timeFrame: 22 months
measure: Phase 2: Determine the Rate of YH001 Immunogenicity
timeFrame: 22 months
measure: Phase 2: Determine the Rate of Envafolimab Immunogenicity
timeFrame: 22 months
measure: Phase 2: Type Incidence and Severity of Adverse Events
timeFrame: 25 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Medical Monitor
name: James Freddo, MD
role: STUDY_DIRECTOR
References: