None listed
Conditions
Brief summary
This is a study evaluating the safety, tolerability and efficacy of CS1003, an new antibody therepy, in participants with advanced, relapsed or refractory solid tumours. Who is it for? You may be eligible for this study if you are aged at least 18 years old and have a confirmed advanced or metastatic tumour, for which treatment is not available, not tolerated or refused. Study details All participants in the study will receive intravenous treatment with the study drug CS1003. The dose may vary depending on when the participant joins the study. A number of tests will be performed, including physical examinations, electrocardiograms, blood and urine tests, CT and/or MRI. It is hoped this study will contribute important safety and efficacy information for this new treatment.
Interventions
All participants will receive treatment with CS1003. Participants enrolled in Phase Ia may receive one of the following doses dependent upon time of enrolment into the study:
Cohort 1: 1 mg/kg
Cohort 2:: 3 mg/kg
Cohort 3: 200 mg
Cohort 4: 10 mg/kg
Participants enrolled in Phase Ib will receive treatment at the MTD or Recommended Phase 2 dose (if less than the MTD) decided upon completion of Phase Ia of the study. The Phase 1b dose will be decided by the Safety Monitoring Committee after revi
All participants will receive treatment with CS1003. Participants enrolled in Phase Ia may receive one of the following doses dependent upon time of enrolment into the study: Cohort 1: 1 mg/kg Cohort 2:: 3 mg/kg Cohort 3: 200 mg Cohort 4: 10 mg/kg Participants enrolled in Phase Ib will receive treatment at the MTD or Recommended Phase 2 dose (if less than the MTD) decided upon completion of Phase Ia of the study. The Phase 1b dose will be decided by the Safety Monitoring Committee after review of the Phase Ia data. CS1003 will be given as an intravenous infusion (through a drip inserted into a vein) over 90 minutes on Day 1 of each 21 day treatment cycle. Participants may receive treatment for up to 34 cycles (or 2 years) or disease progression or intolerance (whichever occurs first). Participants who enrol in Phase Ia of the study are not eligible to enrol in Phase Ib of the study.
Sponsors
CStone Pharmaceuticals Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent for the trial. 2. Male or female and > = 18 years of age on day of signing informed consent. 3. With histologically or cytologically confirmed advanced-stage or metastatic tumour (unresectable) and experienced progression since last anti-tumour treatment with standard therapy; or for which treatment is not available, not tolerated or refused: Phase Ia: Subjects with advanced, relapsed or refractory solid tumours, which should refer to but not limited to the following description for Phase Ib; Phase Ib: Subjects with tumour of specific types: a) Subjects with soft tissue sarcoma (UPS (undifferentiated pleomorphic sarcoma), LPS (dedifferentiated or other high grade liposarcoma)). b) Subjects with malignant pleural mesothelioma (MPM). Subjects with bladder cancer, Merkel-cell carcinoma, gastrointestinal stromal tumour (GIST), gastric cancer, oesophageal carcinoma, small-cell lung cancer (SCLC), large-cell lung cancer (LCLC), head and neck squamous cell carcinoma (HNSCC) or cutaneous squamous cell carcinoma (cuSCC). Any solid tumours with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR). Or other tumour types after discussion with the medical monitor and in consultation with the Sponsor. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. For Phase Ia, participants with evaluable but non-measurable lesion are allowed. For Phase Ib, participants must have at least one measurable lesion per RECIST Version 1.1. 6. Tumor tissue samples need to be collected from the participants for biological marker analysis. The samples can be tumour samples fixed with formalin and embedded in paraffin wax (paraffin wax block or approximately at least 10 unstained slices); for tumour tissue samples that are not archived, the participant has to be willing to undergo biopsy of the tumour focus within 8 weeks before the start of the treatment in order to collect corresponding tumour samples (in quantities determined in accordance with the biopsy results). Subjects may be permitted to enrol on a case-by-case basis after discussion with the medical monitor and in consultation with the Sponsor if tissue or biopsy is not available. 7. Patients with life expectancy > = 3 months. 8. Subject must have adequate organ function (had not received blood transfusion, EPO, G-CSF or other medical support within 14 days before the administration of the study drug): 9. Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 180 days after last study drug administration. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test < = 7 days prior to the first dose of study drug.
Exclusion criteria
1. Known brain metastasis or other CNS metastasis that is either symptomatic or untreated. Central nervous system metastases that have been treated by complete resection and/or radiotherapy demonstrating stability or improvement are not an exclusion criterion provided they are stable as shown by imaging for at least 4 weeks before screening without evidence of cerebral oedema and no requirements for corticosteroids or anticonvulsants. 2. Subjects with active autoimmune diseases or history of autoimmune diseases should be excluded; these include but are not limited to participants with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease including Crohn’s disease and ulcerative colitis, hepatitis, toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or antiphospholipid syndrome. 3. Patients who had to receive glucocorticoids (prednisone at > 10 mg/day or other similar drugs at equivalent dose) or other immunosuppressive medication within 14 days prior to the first dose of the study drug. 4. Phase Ib participants who had other malignant tumour(s) in the past 2 years, except for participants with basal cell carcinoma, in situ breast cancer and cervical carcinoma in situ who had undergone radical treatment. 5. Patients who have received any targeted T-Cell co-regulated proteins (immune checkpoint proteins) antibody/medicine (including PD-1, PD-L1, etc) for treatment. 6. Has had prior chemotherapy, targeted therapy, or any other agents used as systemic treatment for cancer, within 2 weeks prior to the first dose of study drug. 7. Patients who had undergone a major surgical procedure (as defined by the Investigator), or wide field of radiation, within 28 days prior to the first dose of study drug, or received local radiotherapy within 14 days prior to the first dose of study drug, or taken radioactive agents (strontium, samarium, etc.) within 56 days before the first dose of study drug. 8. Patients who had received treatment with Chinese herbal medicine or Chinese prepared medicine within 7 days prior to the first dose of the study drug. 9. Has received a live vaccine within 28 days prior to the first dose of study drug. 10. Has history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies. 11. Known history of HIV infection. 12. Subjects who are Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (HBcAb) positive or Hepatitis C virus (HCV) antibody positive at screening must not be enrolled until further definite testing with Hepatitis B virus (HBV) DNA titres and HCV RNA tests can conclusively rule out presence of active infection (HBV DNA > = 1000 cps/mL or 200 IU/mL) requiring therapy with Hepatitis B and C, respectively. 13. Active infection of tuberculosis. 14. Have signs or symptoms of any active infection requiring systemic therapy. 15. Patients who have received organ transplantation. 16. Any unresolved CTCAE Grade > = 2 toxicities from prior anti-cancer therapy with the exception of vitiligo, alopecia, and the laboratory values defined in the inclusion criteria. 17. History of any irAE of Grade > = 3. 18. Patients who have serious hypersensitive reaction to monoclonal antibodies, and have history of uncontrolled allergic asthma. 19. Patients with known history of alcoholism or drug abuse. 20. Patients with major cardiovascular diseases (e.g.: congestive heart failure, unstable angina pectoris, atrial fibrillation, arrhythmia, etc.): participants who had experienced such diseases as acute myocardial infarction, unstable angina pectoris, apoplexia, or transient ischemic attack within 6 months prior to the first dose of study drug; participants with congestive heart failure of NYHA Grade > = 2; 21. Has known psychiatric disorders that would interfere with cooperation with the requirements of the trial. 22. Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol.
Outcome results
None listed