Status and phase
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Treatments
About
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.
Full 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.
Sex
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Volunteers
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:
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;
At least one measurable lesion per RECISTv1.1; patients without measurable lesions are only acceptable in Dose-Escalation Phase;
Agree to provide tumor tissue samples:
Adequate organ and marrow function, as defined below:
Females of childbearing potential who are sexually active with a non-sterilized male partner must agree to use effective contraception Table 1 starting 72 hours before the first dose until 5 months after the final dose, whichever is later. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as at least 12 months with no menses confirmed by FSH levels performed during the screening period);
Non-sterilized males who are sexually active with a female partner of childbearing potential must agree to use effective contraception from Day 1 through 5 months after receipt of the final dose.
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.
Active or prior documented history of another malignancy within 2 years prior to the first dose of the study drug for patients in Dose-Escalation Phase and Dose Expansion Phase, and active or prior documented history of another malignancy within 5 years prior to the first dose of the study drug for patients in Indication Expansion Phase, with the exception of completely cured early-stage malignancies.
Symptomatic or untreated central nervous system metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 28 days prior to study entry, have no evidence of new or enlarging metastases, and are off steroids.
Unresolved toxicities from prior anticancer therapy, defined as having not resolved to baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion and exclusion criteria with the exception of alopecia. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by JS009, toripalimab and/or JS006 may be included (e.g., hearing loss) after consultation with the medical monitor.
Active or prior documented autoimmune disease within the past 2 years with the following exceptions: vitiligo, alopecia, endocrinopathies controlled by hormone replacement therapy, rheumatoid arthritis and other arthropathies that have not required immunosuppression other than non-steroidal anti-inflammatory agents, celiac disease controlled by diet, or psoriasis controlled with topical medication.
History of primary immunodeficiency.
Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, fever of unknown origin that > 38.5°C (patients with neoplastic fever will be evaluated by the investigator for inclusion or exclusion), symptomatic congestive heart failure according to New York Heart Association (NYHA) Functional Classification ≥ Grade 3, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs from JS009, toripalimab and/or JS006, or compromise the ability of the subject to give written informed consent.
Known history of active tuberculosis within one year. Has difficulty breathing or current need for continuous oxygen inhalation therapy, or current suffering from active pneumonitis (≥ Grade 2) or interstitial lung disease (except mild radiation pneumonitis).
Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
Patients who are known to be human immunodeficiency virus (HIV) positive.
Patients with evidence of hepatitis B or C virus infection, unless their hepatitis is considered to have been cured. (Note that patients with prior hepatitis B virus [HBV] infection must have HBcAb positive, HBsAg negative and have HBV DNA copy number less than the upper limit before study enrollment, and must be treated according to local standards; hepatitis C virus [HCV] infection must have, before study enrollment, negative result of HCV RNA test).
Pregnant women. Women who are lactating must agree to discontinue breast-feeding during treatment and for at least 4 months after the last dose of the study drug, whichever is later;
Any condition that, in the opinion of the investigator, would interfere with evaluation of JS009, toripalimab and/or JS006 or interpretation of patient safety or study results.
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Data sourced from clinicaltrials.gov
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