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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Small Cell Lung Cancer; Non-small Cell Lung Cancer; Thoracic Tumors
• Intervention / Treatment: Drug: ES101

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; ES101 is administered via intravenous infusion, 0.3mg/kg，once every 14 days, every 28 days as a treatment cycle.	Drug: ES101; 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.
Experimental: Cohort 2; ES101 is administered via intravenous infusion, 1mg/kg，once every 14 days, every 28 days as a treatment cycle.	Drug: ES101; 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.
Experimental: Cohort A1; ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.	Drug: ES101; 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.
Experimental: Cohort A2; ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.	Drug: ES101; 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.
Experimental: Cohort B; ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.	Drug: ES101; 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.
Experimental: Cohort C; ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.	Drug: ES101; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1-2 years
Phase 1b: Recommended Phase 2 Dose (RP2D) of of ES101	RP2D of ES101 will be determined.	6 months
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).	2-3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-tumor activity of ES101	Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).	2-4 years
PK profile of ES101	Assess the relationship between ES101 exposure and efficacy/adverse events.	2-4 years
Immunogenicity of ES101	Frequency of anti-drug antibodies (ADA) against ES101 will be determined.	2-4 years
Pharmacodynamic markers	Assess PD-L1 receptor occupancy and cytokines	2-4 years
PD-L1 expression	Assess PD-L1 expression status of tumor tissues	2-4 years

Collaborators and Investigators

• Sponsor: Elpiscience Biopharma, Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: April 8, 2021
• First Submitted That Met QC Criteria: April 8, 2021
• First Posted (Actual): April 12, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: PD-L1; PDL1; 4-1BB; ES101; INBRX-105; PD-L1×4-1BB; 41BB; Thoracic Tumor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Thoracic Neoplasms
• Other Study ID Numbers: ES101-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No