None listed
Conditions
Brief summary
Study Purpose This study aims to evaluate a new investigational treatment called IMD303 to determine a safe dose and understand how the body responds to it in people with advanced solid cancers. Who Can Participate? You may be eligible for this study if you are aged 18 years or older and have an advanced or recurrent solid tumour such as melanoma, non-small cell lung cancer, renal cell carcinoma, hepatocellular carcinoma, or bladder cancer and whose cancer has progressed despite standard treatment, who cannot tolerate standard treatment, or who have chosen not to pursue further standard therapy. Study details Those who are eligible will receive IMD303 as an intravenous infusion on Day 1 of each treatment cycle. Each dose level will include around 3 to 6 participants, and there is an element of chance because participants are enrolled into sequential dose groups depending on when they join the study. Study Duration The anticipated study duration for each participant in Phase 1a is at least four treatment cycles (each cycle is of 21 days). The Safety Monitoring Committee may assess whether the treatment could continue beyond Cycle 8 based on the emerging evidence of clinical benefit (e.g., partial or complete response). Potential Benefits It is hoped that this research will help determine whether IMD303 is safe and how it affects cancer growth, providing important early information that may support the development of new treatment options in the future.
Interventions
This is a dose-escalation study evaluating IMD303 in participants with advanced malignant solid tumors. IMD303 will be administered as an intravenous (IV) infusion on Day 1 of each treatment cycle.
Initially, one participant is enrolled into each dose group and monitored for at least seven days following administration for early detection of dose-limiting toxicities (DLTs) and for minimizing the risk of exposing additional participants to potentially harmful effects. If no DLTs are observed, tw
This is a dose-escalation study evaluating IMD303 in participants with advanced malignant solid tumors. IMD303 will be administered as an intravenous (IV) infusion on Day 1 of each treatment cycle. Initially, one participant is enrolled into each dose group and monitored for at least seven days following administration for early detection of dose-limiting toxicities (DLTs) and for minimizing the risk of exposing additional participants to potentially harmful effects. If no DLTs are observed, two more participants are then enrolled at the same dose level, validating its tolerability before moving to a higher dose. If no dose-limiting toxicities are reported during the 21-day observation period, dose escalation may proceed to the next dose level until the maximum dose specified in the study is reached. After completing Cycle 1, participants may continue to receive IMD303 once every 3 weeks for up to 4 cycles initially. If, after completing 4 cycles, the investigator determines that safety is manageable and the participant is benefiting from treatment, and with the sponsor’s approval, treatment may be extended to Cycles 5 through 8. Each dose cohort will enroll approximately 3 to 6 participants. The starting dose of IMD303 is set at 5 mg/kg. The dose-escalation phase includes 5 mg/kg, 10 mg/kg, 20 mg/kg, 27 mg/kg, and 36 mg/kg. If safety is acceptable, the maximum planned dose is 50 mg/kg or higher. The study will be conducted at multiple sites in Australia and China. It will include a screening period of up to 28 days, a treatment period, an end of treatment visit, and a safety follow up. The anticipated study duration for each participant is at least four treatment cycles.
Sponsors
Catalysis Therapeutics Pty Ltd/Affinity (Chengdu) Pharmaceutical Co., Ltd
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. A written informed consent form must be signed prior to performing any study procedures. 2. Males or females over 18 years of age (inclusive). 3. Diagnosis of advanced or recurrent, histologically or cytologically confirmed solid malignancy for which these participants have received standard treatment but still developed disease progression, or the participants declined any further standard treatment, or the participant was intolerable to the standard treatment. • Phase 1 Dose Escalation: solid tumors types including melanoma, non-small cell lung cancer [NSCLC], renal cell carcinoma, hepatocellular carcinoma and bladder cancer, etc. 4. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. 5. Participants must have a life expectancy of >=3 months. 6. Participants must demonstrate measurable disease, per RECIST v1.1. 7. Participants must have adequate hematologic and organ function as indicated by the following laboratory values a. Hematologic • The participant must not have received treatment with erythropoietin (EPO), granulocyte- colony stimulating factor (G-CSF), or granulocyte-macrophage colony stimulating factor (GM-CSF) within 14 days prior to the first dose, and must not have received any blood transfusion (including red blood cell or platelet transfusion) within at least 7 days. • Absolute neutrophil count >=1.5*10^9/L • Platelet count >=90*10^9/L • Hemoglobin >=9 g/dL b. Renal • Creatinine clearance rate > 50 mL/min (calculated by Cockcroft-Gault formula) c. Hepatic • Aspartate aminotransferase levels <=3*upper limit of normal (ULN) (if liver metastases are present, <=5*ULN) • Alanine aminotransferase levels <=3*ULN (if liver metastases are present, <=5*ULN) • Total bilirubin <=1.5*ULN or <=3*ULN in the presence of documented Gilbert’s Syndrome or liver metastases at baseline d. Coagulation • Prothrombin time and active partial thromboplastin time <=1.5*ULN • International normalized ratio (INR) <=1.5*ULN 8. Female participants of child-bearing potential must have a negative blood pregnancy test within 7 days before enrollment. 9. Eligible participants of reproductive age (female) must agree to use a reliable method of contraception (hormonal, barrier method or abstinence) with their partner during the trial period and for at least 6 months after the last dosing. This requirement does not apply to infertile women who have undergone surgical sterilization (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the screening visit or postmenopausal women who have not menstruated for 12 months for no other medical reason and whose follicle-stimulating hormone levels are consistent with postmenopausal status. 10. Male participant with a female partner of child-bearing potential is eligible to participate but must be either documented to be surgically sterile (vasectomy), practicing complete abstinence during the trial and for 3 months after last dosing of study drug, or using two adequate forms of highly effective contraception (together with the female partner), one of which should be a physical barrier method, during the trial and for 3 months after last dosing of study drug. Participants must be willing and able to comply with all scheduled visits, treatment, laboratory tests, and other requirements of the study.
Exclusion criteria
1. Participants who have received antitumor treatments such as traditional Chinese anti-cancer herbal therapy, chemotherapy, radiotherapy, biotherapy, and endocrine therapy within 4 weeks prior to the first administration are excluded: a) Those who have received nitrosourea or mitomycin C treatment within 6 weeks prior to the first administration b) Those who have received oral fluorouracil and small molecule targeted drugs within 2 weeks prior to the first administration or over 5 half-lives of the drug (whichever is longer). 2. Participants who have received unapproved experimental drugs or treatments within 4 weeks prior to the first administration. 3. Participants who have undergone major surgeries (except for biopsy) or suffered major trauma within 4 weeks prior to the first administration or need to undergo elective surgeries during the trial period. 4. Participants who have previously received an anti-CD137 antibody or other immune therapies specifically targeting T cells (such as CAR T, TIL therapy) or CTLA-4 targeted therapy (such as monoclonal antibody) within six months. 5. Participants who have used systemic corticosteroids (prednisone >10 mg/day or equivalent doses of similar drugs) or other immunosuppressants within 14 days prior to the first administration are excluded, except for the following: a) The use of topical, ocular, intra-articular, intranasal, or inhaled corticosteroids; short-term prophylactic use of corticosteroids (for example, to prevent contrast agent allergy). 6. Participants whose adverse reactions from previous antitumor treatments have not recovered to Grade 1000 copy/mL or >200 IU/mL); hepatitis C virus infection (requiring both HCV-Ab positive and HCV-RNA positive); HIV (antibody test positive); active syphilis (positive syphilis spiral antibody and positive RPR); or active tuberculosis infection (combined medical history, imaging with other clinical examination methods). 7. Participants with a history of severe cardiovascular and cerebrovascular diseases, including but not limited to: a) Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention and second- to third-degree atrioventricular block. b) Corrected QT interval (QTc) >470 ms in males and >480 ms in females in resting 12 lead ECG (Fridericia’s formula). c) Participants with acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular diseases within 6 months prior to the first administration, which are judged by the investigator to impair the participant's tolerance to the treatment used in this clinical study protocol or significantly increase the risk of complications. d) New York Heart Association cardiac function class >=II, left ventricular ejection fraction 1000 mL within 1 week or a single drainage of pleural and ascitic fluid >500 mL within 1 week), judged by the investigator as unsuitable for the study. 8. Participants with active, chronic, or recurrent (within 1 year before signing the informed consent) severe autoimmune diseases or a history of immune-mediated diseases requiring glucocorticoid or other immunosuppressive treatments, except for hypothyroidism that can be controlled only by hormone replacement therapy and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis). 9. Participants with mental disorders or known alcohol/drug dependence, or participants with poor compliance who cannot comply with the study and follow up procedures. 10. Pregnant or lactating women. 11. Have received live vaccines administered within 30 days of the first drug administration 12. Participants judged as unqualified by the investigator and Sponsor due to other serious systemic disease histories or other reasons.
Outcome results
None listed