NCT05448820

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Nov 2022

Typical duration for phase_1

Geographic Reach
1 country

6 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 28, 2022

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 7, 2022

Completed
4 months until next milestone

Study Start

First participant enrolled

November 14, 2022

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2023

Completed
1.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2025

Completed
Last Updated

September 21, 2023

Status Verified

September 1, 2023

Enrollment Period

12 months

First QC Date

June 28, 2022

Last Update Submit

September 19, 2023

Conditions

Keywords

TraconSTSLMSDDLSASPSenvafolimabYH001CTLA-4PD-L1chondrosarcoma

Outcome Measures

Primary Outcomes (4)

  • 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 Outcomes (14)

  • Phase 1: YH001 concentrations

    8 months

  • Phase 1: Envafolimab concentrations

    8 months

  • Phase 1: Determine the Rate of YH001 Immunogenicity

    8 months

  • Phase 1: Determine the Rate of Envafolimab Immunogenicity

    8 months

  • Phase 1: Assessment of antitumor activity

    8 months

  • +9 more secondary outcomes

Study Arms (8)

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

EXPERIMENTAL

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

Drug: YH001Drug: Envafolimab

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

EXPERIMENTAL

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

Drug: YH001Drug: Envafolimab

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

EXPERIMENTAL

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

Drug: YH001Drug: EnvafolimabDrug: Doxorubicin

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

EXPERIMENTAL

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

Drug: YH001Drug: EnvafolimabDrug: Doxorubicin

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

EXPERIMENTAL

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

Drug: YH001Drug: Envafolimab

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

EXPERIMENTAL

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

Drug: YH001Drug: Envafolimab

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

EXPERIMENTAL

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: YH001Drug: EnvafolimabDrug: Doxorubicin

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

EXPERIMENTAL

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: YH001Drug: EnvafolimabDrug: Doxorubicin

Interventions

YH001DRUG

Anti-CTLA4 antibody

P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WKP1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WKP1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WKP1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WKP2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WKP2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WKP2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WKP2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK

Anti-PD-L1 antibody

Also known as: KN035
P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WKP1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WKP1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WKP1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WKP2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WKP2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WKP2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WKP2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK

Anthracycline

P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WKP1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WKP2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WKP2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Links

MeSH Terms

Conditions

SarcomaDiabetes Mellitus, Insulin-Dependent, 12Chondrosarcoma

Interventions

envafolimabDoxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsNeoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

DaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydrates

Study Officials

  • James Freddo, MD

    Medical Monitor

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 28, 2022

First Posted

July 7, 2022

Study Start

November 14, 2022

Primary Completion

November 1, 2023

Study Completion

September 1, 2025

Last Updated

September 21, 2023

Record last verified: 2023-09

Locations