A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of JS009 Monotherapy and JS009 as a Triple Combination Therapy in Combination With Toripalimab and JS006 in Patients With Advanced Malignancies
Overview
- Phase
- Phase 1
- Intervention
- JS009 as a monotherapy and JS009 as a Triple Combination Therapy in Combination with Toripalimab and JS006
- Conditions
- Primary Condition: Advanced Tumors
- Sponsor
- Shanghai Junshi Bioscience Co., Ltd.
- Primary Endpoint
- Incidence of DLT
- Status
- Withdrawn
- Last Updated
- 3 years ago
Overview
Brief Summary
The study is being conducted to evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy JS009 as a monotherapy and JS009 as a Triple Combination Therapy in Combination with Toripalimab and JS006 in Patients with Advanced Malignancies, also to explore the RP2D of JS009.
Detailed Description
This is an open-label, Phase I study contains dose escalation phase, dose expansion phase and indication expansion phase. The dose escalation phase will be following the accelerated titration design and the classic 3+3 design, with a planned enrollment of 13 to 30 patients with advanced tumors. The dose expansion phase will be used safe and tolerable doses, with a planned enrollment of 9 to 24 patients with advanced tumors. The indication expansion phase will selecte different primary malignancies for investigation of anti-tumor activity. Each Cohort planned to enrollment 20-50 patients with advanced tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able to understand and voluntarily sign the informed consent form (ICF);
- •Males and females, ≥18 years of age;
- •Histopathology confirmed patients with advanced solid malignancies;
- •Patients who have experienced disease progression on standard therapy, be ineligible for or intolerant of available approved standard therapies known to confer clinical benefit or for whom no effective standard therapy exists; In Indication Expansion Phase, prior tumor types include, but are not limited to:
- •Cohort 1 Non-Small Cell Lung Cancer (NSCLC): patients with locally advanced or metastatic NSCLC, disease recurrence or progression during or after prior therapy with or without anti-PD-(L)1 therapy. The patients must have no known activating EGFR mutations or ALK fusion.
- •Cohort 2 Endometrial Cancer(EC): patients with locally advanced or metastatic EC, disease recurrence or progression during or after prior therapy that included platinum-based chemotherapy.
- •Cohort 3 Ovarian Cancer(OC): patients with locally advanced or metastatic OC, disease recurrence or progression during or after prior therapy that included platinum-based chemotherapy.
- •Cohort 4 Colorectal Cancer(CRC): patients with locally advanced or metastatic CRC, disease recurrence or progression during or after prior therapy with or without anti-PD-(L)1 therapy.
- •In Indication Expansion Phase, prior standard therapy should be ≤ three lines of treatment;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and expected survival ≥12 weeks;
Exclusion Criteria
- •Moderate to severe hypersensitivity reaction to toripalimab or other PD-1 blocking antibodies or known allergy to the component of JS009 and JS006 drug product.
- •Prior exposure to antibodies targeting TIGIT, CD112R, CD155, CD113 or related ligands.
- •Concurrent enrollment in another clinical study, or participated in another clinical study within 21 days prior to the first dose of the study drug, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
- •Major surgery within 28 days prior to the first dose of the study drug or still recovering from prior surgery.
- •Current or prior use of chemotherapy, radiotherapy, immunotherapy, biologic therapy and targeted therapy within 21 days prior to the first dose of the study drug (Nitrosourea and Mitomycin require 6 weeks interval time between the last dose of chemotherapy and the first dose of the study drug); except： i. The wash-out period for oral medicine is 5 half-lives after discontinuation. ii. The wash-out period is 14 days for palliative radiotherapy (eg. bone radiotherapy to control pain) which has no effect on bone marrow haematopoietic function.
- •iii. long-term and stabile hormone therapy. Also, use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable.
- •Patients with immune-related AEs/SAEs that have led to permanent discontinuation of immune therapies, previously.
- •Current or prior use of immunosuppressive medication within 28 days prior to the first dose of the study drug, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids ≤ 10 mg/day of prednisone or equivalent.
- •Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
- •Receipt of live attenuated vaccination within 30 days prior to the first dose of the study drug.
Arms & Interventions
JS009 as a monotherapy and JS009 Combine with Toripalimab and JS006
1. JS009 as Monotherapy in first cycle of dose escalation and the triple combination therapy will be administered in subsequent cycles：5 proposed dose levels（18mg, 60mg, 180mg, 600mg, 1200mg). 2. The triple combination therapy in dose expansion：1 or 2 proposed dose levels, to be determined. 3. The triple combination therapy in indication expansion：4 or more cohorts, to be determined.
Intervention: JS009 as a monotherapy and JS009 as a Triple Combination Therapy in Combination with Toripalimab and JS006
Outcomes
Primary Outcomes
Incidence of DLT
Time Frame: Within the DLT window of the first 2 cycles(42 days) in dose escalation phase
The Incidence of subjects with adverse event meeting the criteria of dose-limiting toxicity（DLT） in 42 days during dose escalation phase
Incidence and severity of AE as assessed by CTCAE v5.0
Time Frame: Approximately 2 years.
The incidence and severity of adverse events (AE)
MTD
Time Frame: Approximately 2 years.
The highest dose at which no more than 0 of 3 or 1 of 6 patients experienced a DLT during Cycle 1 and 2 during dose escalation phase.
RP2D
Time Frame: Approximately 2 years.
Recommended phase II dose (RP2D) for JS009 monotherapy and combination therapy
Secondary Outcomes
- Drug concentration in plasma(Approximately 2 years.)
- Immunogenicity(Approximately 2 years.)
- ORR(Approximately 2 years.)