None listed
Conditions
Brief summary
Study Purpose This study aims to evaluate IMD303, a new investigational treatment, in combination with another drug known as PD-1 inhibitor to determine a safe and tolerable dose and to characterize how the two agents interact in individuals with advanced solid cancers. Who Can Participate? You may be eligible for this study if you are aged 18 years or older and have selected tumor type expansion like melanoma, renal cell carcinoma and hepatocellular carcinoma 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. The IMD303 dose will be given at least minutes after administration of a PD-1 inhibitor. Each group will have about 5 to 10 participants. Because people are enrolled one after another into the next available dose group, the dose they receive depends on when they join the study. Study Duration The anticipated study duration for each participant in Phase 1b/II is at least 8 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 the study will help determine whether IMD303 when given together with a PD-1 inhibitor is safe and how the combination affects cancer growth. The data may provide important early information to support the future development of new treatment options.
Interventions
This Phase Ib/II expansion study of IMD303 will be initiated following completion of the Phase Ia study. It will enroll participants with selected tumor types (e.g., melanoma, renal cell carcinoma and hepatocellular carcinoma). The study will include a screening period of up to 28 days, a treatment period, an end-of-treatment visit, and a safety follow-up assessment. Participants in Phase Ib/II will be allocated based on investigator discretion. The Phase Ib cohort expansion will consist of two
This Phase Ib/II expansion study of IMD303 will be initiated following completion of the Phase Ia study. It will enroll participants with selected tumor types (e.g., melanoma, renal cell carcinoma and hepatocellular carcinoma). The study will include a screening period of up to 28 days, a treatment period, an end-of-treatment visit, and a safety follow-up assessment. Participants in Phase Ib/II will be allocated based on investigator discretion. The Phase Ib cohort expansion will consist of two tumor-specific cohorts, each enrolling approximately 3 to 6 participants. These cohorts will further explore safety, tolerability, and preliminary activity in the selected tumor types. In Phase II cohort expansion, several cohorts (10 to 40 participants/cohort) will be selected for specific tumor-type expansion. Group 1: IMD303 (e.g., 30 milligram per kilogram [mg/kg] if determined safe based on data from Phase Ia) intravenous infusion for 60 (±10) minutes follows PD-1 inhibitor (e.g., nivolumab 240 mg); every 3 weeks for 8 cycles and then PD-1 inhibitor alone every 2 weeks for 8 cycles. The first infusion of IMD303 takes at least 90 minutes. Group 2: IMD303 (e.g., 40 mg/kg if determined safe based on data from Phase Ia) intravenous infusion for 60 (±10) minutes follows PD-1 inhibitor (e.g., nivolumab 240 mg), every 3 weeks for 8 cycles and then only PD-1 inhibitor every 2 weeks for 8 cycles. The first infusion of IMD303 takes at least 90 minutes. The PD-1 inhibitor must be infused intravenously first, followed by IMD303. The infusion of IMD303 should commence no earlier than 30 minutes after completion of the PD-1 inhibitor infusion, ensuring adequate separation between administrations. Dosing in both the groups will be done in parallel assignment. All procedures, including dosing, will be documented by delegated site staff within the participant source records. Participants will not self-administer any dosing; therefore, adherence is not relevant. Phase II cohort expansion will have several cohorts (10 to 40 participants/cohort) and will be selected for specific tumor-type expansion. The Phase II study includes multiple tumor-specific cohorts, the selection and prioritization of which will be informed by the safety, pharmacokinetic, pharmacodynamic and preliminary efficacy data obtained from Phase Ib study. The Phase Ib data will help investigators determine which combination group (IMD303 at 30 mg/kg with PD-1 inhibitor or IMD303 at 40 mg/kg with PD-1 inhibitor) is appropriate in respect of safety, tolerability, and efficacy for the Phase II study. The total treatment period for Phase II part is approximately up to 24 weeks (8 cycles). Phase II part will include participants from Phase 1b part, who are willing to and fulfil the inclusion criteria and additionally will include new participants in specific tumor-type expansion cohorts (example; melanoma, renal cell carcinoma, hepatocellular carcinoma etc.). The total treatment period for the Phase 1b/II part is approximately up to 2 years.
Sponsors
Catalysis Therapeutics Pty Ltd/Affinity (Chengdu) Pharmaceutical Co., Ltd
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
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 Ib/II Dose Expansion: the following tumor types are tentatively planned for expansion. They may be modified based on the results from the dose escalation phase: - melanoma - renal cell carcinoma - hepatocellular carcinoma 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