Clinical trial NCT04841538: 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
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Elpiscience Biopharma, Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-12
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Phase 1b: Frequency and severity of adverse events of ES101
timeFrame: 1-2 years
measure: Phase 1b: Recommended Phase 2 Dose (RP2D) of of ES101
timeFrame: 6 months
measure: Phase 2: Objective response rate (ORR)
timeFrame: 2-3 years
Secondary outcomes:
measure: Anti-tumor activity of ES101
timeFrame: 2-4 years
measure: PK profile of ES101
timeFrame: 2-4 years
measure: Immunogenicity of ES101
timeFrame: 2-4 years
measure: Pharmacodynamic markers
timeFrame: 2-4 years
measure: PD-L1 expression
timeFrame: 2-4 years
Other outcomes:
Locations:
Study officials:
References: