A Study of ES101 (PD-L1x4-1BB Bispecific Antibody) in Patients With Advanced Malignant Thoracic Tumors
Phase 1
Withdrawn
- Conditions
- Non-small Cell Lung CancerSmall Cell Lung CancerThoracic Tumors
- Interventions
- Registration Number
- NCT04841538
- Lead Sponsor
- Elpiscience Biopharma, Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort B ES101 ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle. Cohort 1 ES101 ES101 is administered via intravenous infusion, 0.3mg/kg，once every 14 days, every 28 days as a treatment cycle. Cohort A2 ES101 ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle. Cohort 2 ES101 ES101 is administered via intravenous infusion, 1mg/kg，once every 14 days, every 28 days as a treatment cycle. Cohort A1 ES101 ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle. Cohort C ES101 ES101 is administered via intravenous infusion, RP2D (to be determined)，once every 14 days, every 28 days as a treatment cycle.
- Primary Outcome Measures
Name Time Method Phase 1b: Recommended Phase 2 Dose (RP2D) of of ES101 6 months RP2D of ES101 will be determined.
Phase 1b: Frequency and severity of adverse events of ES101 1-2 years Adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Phase 2: Objective response rate (ORR) 2-3 years Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).
- Secondary Outcome Measures
Name Time Method PD-L1 expression 2-4 years Assess PD-L1 expression status of tumor tissues
Anti-tumor activity of ES101 2-4 years Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).
PK profile of ES101 2-4 years Assess the relationship between ES101 exposure and efficacy/adverse events.
Immunogenicity of ES101 2-4 years Frequency of anti-drug antibodies (ADA) against ES101 will be determined.
Pharmacodynamic markers 2-4 years Assess PD-L1 receptor occupancy and cytokines