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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04841538
• Other study ID #: ES101-2001
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: July 2021
• Est. completion date: May 2024

Study information

• Verified date: April 2022
• Source: Elpiscience Biopharma, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Neoplasms
• Non-small Cell Lung Cancer
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Thoracic Neoplasms
• Thoracic Tumors

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Elpiscience Biopharma, Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase 1b: Recommended Phase 2 Dose (RP2D) of of ES101	RP2D of ES101 will be determined.	6 months
Primary	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	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
Secondary	PK profile of ES101	Assess the relationship between ES101 exposure and efficacy/adverse events.	2-4 years
Secondary	Immunogenicity of ES101	Frequency of anti-drug antibodies (ADA) against ES101 will be determined.	2-4 years
Secondary	Pharmacodynamic markers	Assess PD-L1 receptor occupancy and cytokines	2-4 years
Secondary	PD-L1 expression	Assess PD-L1 expression status of tumor tissues	2-4 years