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

NCT04009460 | Terminated Phase 1

• 2 other identifiers: ES101-1001CTR20190888
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerance and Dose-Limiting Toxicity (DLT) of recombinant humanized PD-L1/4-1BB bispecific antibody (ES101) in patients with advanced solid tumors.

Conditions

Solid Tumors; Neoplasms; Malignant Tumor

Keywords

ES101; solid tumor; phase 1; PD-L1; 4-1BB; INBRX-105; PD-L1×4-1BB; 41BB; PDL1

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of of ES101

  The MTD and/or RP2D of ES101 will be determined.

  Up to 2-3 years

• Frequency of adverse events of ES101

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

  Up to 2-3 years

• Severity of adverse events of ES101

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

  Up to 2-3 years

Secondary Outcomes (6)

• Area under the serum concentration time curve (AUC) of ES101

  Up to 2-3 years

• Maximum observed serum concentration (Cmax) of ES101

  Up to 2-3 years

• Trough observed serum concentration (Ctrough) of ES101

  Up to 2-3 years

• Time to Cmax (Tmax) of ES101

  Up to 2-3 years

• Immunogenicity of ES101

  Up to 2-3 years

Study Arms (2)

Part A dose escalation

EXPERIMENTAL

ES101 will be escalated in patients with advanced solid tumors.

Drug: ES101

Part B expansion

EXPERIMENTAL

Subjects with solid tumors will be treated with single-agent ES101 at either specified dose levels or RP2D.

Drug: ES101

Interventions

ES101 DRUG

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

Part A dose escalation; Part B expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged ≥ 18 years.
• Subject has pathological or cytological diagnosed advanced malignant solid tumor, whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options
• Part A: There is no mandatory requirement for PD-L1 expression status of subject's tumor tissue. Part B:Tumor tissue of subject should be PD-L1 positivity by immunohistochemistry (IHC).
• Subjects in part A shall have at least one evaluable lesion, and subjects enrolled in part B shall have at least one measurable lesion (RECIST v1.1). Tumor lesions located in previously irradiated (or other local treated) areas will be considered measurable, provided that there has been clear imaging-based progression of the lesions since the time of radiation.
• Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• Estimated life expectancy, in the judgment of the investigator, of at least 12 weeks.
• Male and female subjects of childbearing potential and their spouses must be willing to use feasible contraceptive methods considered effective by the investigator, from the time of signing informed consent and for the duration of study participation through 3 months, following the last dose of study drug. Postmenopausal women are considered to have no fertility potential only if menostasis lasts for at least 12 months.
• Ability to understand and the willingness to sign a written informed consent form

You may not qualify if:

• 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.
• Known allergies to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to ES101.
• Primary or metastatic brain or meningeal tumors.
• Patients with other malignancies previously or currently shall be excluded in Part B.
• Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per 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.
• Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. 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 immunosuppressive medications..
• Subjects who received G-CSF, GM-CSF, Thrombopoietic drugs or EPO within 14 days prior to the first dose of the study drug.
• Any evidence of hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
• History of hepatitis (non-alcohol steatohepatitis, alcohol or drug-related, autoimmune) or cirrhosis.
• Clinically significant cardiac condition.
• History of pulmonary embolism within 12 weeks prior to the first dose of study drug.
• Major surgery within 4 weeks prior to enrollment on this trial.

Sponsors & Collaborators

• Elpiscience Biopharma, Ltd.: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 201203, China

Location

MeSH Terms

Conditions

Neoplasms

Study Design

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

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 5, 2019
• Study Start: June 28, 2019
• Primary Completion: April 22, 2022
• Study Completion: April 22, 2022
• Last Updated: April 29, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)