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

Tracon Pharmaceuticals

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Soft Tissue Sarcoma; Advanced Sarcoma; Metastatic Sarcoma

Treatments: Drug: YH001; Drug: Doxorubicin; Drug: Envafolimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05448820

YH001/KN035SAR101

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 8 patient groups

P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WK

Experimental group

Description:

Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.

Treatment:

Drug: Envafolimab

Drug: YH001

P1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WK

Experimental group

Description:

Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.

Treatment:

Drug: Envafolimab

Drug: YH001

P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK

Experimental group

Description:

Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.

Treatment:

Drug: Envafolimab

Drug: Doxorubicin

Drug: YH001

P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK

Experimental group

Description:

Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.

Treatment:

Drug: Envafolimab

Drug: Doxorubicin

Drug: YH001

P2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WK

Experimental group

Description:

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks

Treatment:

Drug: Envafolimab

Drug: YH001

P2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WK

Experimental group

Description:

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks

Treatment:

Drug: Envafolimab

Drug: YH001

P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK

Experimental group

Description:

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

Treatment:

Drug: Envafolimab

Drug: Doxorubicin

Drug: YH001

P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK

Experimental group

Description:

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

Treatment:

Drug: Envafolimab

Drug: Doxorubicin

Drug: YH001