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A Study of ES101 (PD-L1x4-1BB Bispecific Antibody) in Patients With Advanced Malignant Thoracic Tumors

Primary Purpose

Thoracic Tumors, Non-small Cell Lung Cancer, Small Cell Lung Cancer

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

ES101

About this trial

This is an interventional treatment trial for Thoracic Tumors focused on measuring ES101, INBRX-105, PD-L1, 4-1BB, PD-L1×4-1BB, PDL1, 41BB, Thoracic Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Ability to understand and the willingness to sign a written informed consent form.
Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
At least one measurable lesion is required (RECIST v1.1)
Phase 1b: Subjects with pathologically or cytologically confirmed recurrent or metastatic NSCLC without known EGFR mutation and ALK and ROS1 gene rearrangements.
Phase II: Subjects with pathologically or cytologically confirmed recurrent or metastatic malignant thoracic tumours who have received 1-2 lines of systemic anti-tumour therapy, including platinum regimens, and have failed, including at least 2 cycles of chemotherapy.

Exclusion Criteria:

Prior exposure to 4-1BB agonists.
Receipt of any anticancer investigational product or any approved drug(s) or biological products (except hormone-replacement therapy, testosterone or oral contraceptives) within 4 weeks prior to the first dose of study drug. Previous exposure to oral fluorouracils or small molecular targeted drugs require a minimum washout period of 2 weeks or 5 half-lives prior to the first dose of study drug (whichever is longer). Previous exposure to mitomycin C or nitrosourea requires a minimum washout period of 6 weeks prior to the first dose of study drug.
Receipt of PD-L1 therapy within 24 weeks prior to the first dose of study drug.
Known allergies to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to ES101.
Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply.
Subject has not recovered from all AEs of previous anticancer therapies to baseline or ≤ Grade 1 per CTCAE v5.0 before teh first dose of study drug. Certain exceptions as defined in protocol apply.
Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply.
Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications.
Systemic anti-infectious drug treatments within 4 weeks prior to the first dose of study drug.
Pregnant or nursing females.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort A1

Cohort A2

Cohort B

Cohort C

Arm Description

ES101 is administered via intravenous infusion, 0.3mg/kg，once every 14 days, every 28 days as a treatment cycle.

ES101 is administered via intravenous infusion, 1mg/kg，once every 14 days, every 28 days as a treatment cycle.

ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.

Outcomes

Primary Outcome Measures

Phase 1b: Frequency and severity of adverse events of ES101

Adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Phase 1b: Recommended Phase 2 Dose (RP2D) of of ES101

RP2D of ES101 will be determined.

Phase 2: Objective response rate (ORR)

Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).

Secondary Outcome Measures

Anti-tumor activity of ES101

Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).

PK profile of ES101

Assess the relationship between ES101 exposure and efficacy/adverse events.

Immunogenicity of ES101

Frequency of anti-drug antibodies (ADA) against ES101 will be determined.

Pharmacodynamic markers

Assess PD-L1 receptor occupancy and cytokines

PD-L1 expression

Assess PD-L1 expression status of tumor tissues

Full Information

NCT ID

NCT04841538

First Posted

April 8, 2021

Last Updated

April 22, 2022

Sponsor

Elpiscience Biopharma, Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04841538

Brief Title

A Study of ES101 (PD-L1x4-1BB Bispecific Antibody) in Patients With Advanced Malignant Thoracic Tumors

Official Title

An Open-label, Multicenter, Multicohort Phase 1b/2 Clinical Trial of ES101 in Patients With Advanced Malignant Thoracic Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor's clinical development strategy adjustment

Study Start Date

July 2021 (Anticipated)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Elpiscience Biopharma, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety, RP2D and PK/pharmacodynamic profile of ES101 monotherapy in patients with advanced NSCLC and to further evaluate the antitumor efficacy of ES101 in advanced malignant thoracic tumors, including NSCLC and SCLC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thoracic Tumors, Non-small Cell Lung Cancer, Small Cell Lung Cancer

Keywords

ES101, INBRX-105, PD-L1, 4-1BB, PD-L1×4-1BB, PDL1, 41BB, Thoracic Tumor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

ES101 is administered via intravenous infusion, 0.3mg/kg，once every 14 days, every 28 days as a treatment cycle.

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

ES101 is administered via intravenous infusion, 1mg/kg，once every 14 days, every 28 days as a treatment cycle.

Arm Title

Cohort A1

Arm Type

Experimental

Arm Description

ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.

Arm Title

Cohort A2

Arm Type

Experimental

Arm Description

ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.

Arm Title

Cohort B

Arm Type

Experimental

Arm Description

ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.

Arm Title

Cohort C

Arm Type

Experimental

Arm Description

ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.

Intervention Type

Drug

Intervention Name(s)

ES101

Intervention Description

The active ingredient of ES101 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.

Primary Outcome Measure Information:

Title

Phase 1b: Frequency and severity of adverse events of ES101

Description

Adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

Time Frame

1-2 years

Title

Phase 1b: Recommended Phase 2 Dose (RP2D) of of ES101

Description

RP2D of ES101 will be determined.

Time Frame

6 months

Title

Phase 2: Objective response rate (ORR)

Description

Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).

Time Frame

2-3 years

Secondary Outcome Measure Information:

Title

Anti-tumor activity of ES101

Description

Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).

Time Frame

2-4 years

Title

PK profile of ES101

Description

Assess the relationship between ES101 exposure and efficacy/adverse events.

Time Frame

2-4 years

Title

Immunogenicity of ES101

Description

Frequency of anti-drug antibodies (ADA) against ES101 will be determined.

Time Frame

2-4 years

Title

Pharmacodynamic markers

Description

Assess PD-L1 receptor occupancy and cytokines

Time Frame

2-4 years

Title

PD-L1 expression

Description

Assess PD-L1 expression status of tumor tissues

Time Frame

2-4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent form. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. At least one measurable lesion is required (RECIST v1.1) Phase 1b: Subjects with pathologically or cytologically confirmed recurrent or metastatic NSCLC without known EGFR mutation and ALK and ROS1 gene rearrangements. Phase II: Subjects with pathologically or cytologically confirmed recurrent or metastatic malignant thoracic tumours who have received 1-2 lines of systemic anti-tumour therapy, including platinum regimens, and have failed, including at least 2 cycles of chemotherapy. Exclusion Criteria: Prior exposure to 4-1BB agonists. Receipt of any anticancer investigational product or any approved drug(s) or biological products (except hormone-replacement therapy, testosterone or oral contraceptives) within 4 weeks prior to the first dose of study drug. Previous exposure to oral fluorouracils or small molecular targeted drugs require a minimum washout period of 2 weeks or 5 half-lives prior to the first dose of study drug (whichever is longer). Previous exposure to mitomycin C or nitrosourea requires a minimum washout period of 6 weeks prior to the first dose of study drug. Receipt of PD-L1 therapy within 24 weeks prior to the first dose of study drug. Known allergies to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to ES101. Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply. Subject has not recovered from all AEs of previous anticancer therapies to baseline or ≤ Grade 1 per CTCAE v5.0 before teh first dose of study drug. Certain exceptions as defined in protocol apply. Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply. Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications. Systemic anti-infectious drug treatments within 4 weeks prior to the first dose of study drug. Pregnant or nursing females.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

A Study of ES101 (PD-L1x4-1BB Bispecific Antibody) in Patients With Advanced Malignant Thoracic Tumors

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