An Open-Label, Multicenter, First-in-Human Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of SIM0610 in Adult Subjects With Locally Advanced/Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 260
- Locations
- 7
- Primary Endpoint
- Dose Limiting Toxicity (DLT)
Overview
Brief Summary
This is a multicenter, open-label, first-in-human (FIH) study to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic profile, and preliminary antitumor activity of SIM0610 in subjects with locally advanced/metastatic solid tumors. Accelerated titration (ATD) and Bayesian optimal interval design (BOIN) will be used to guide dose escalation in part1, the preliminary anti-tumor effect of SIM0610 will to be further evaluated in part 2.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily participate and sign the informed consent form
- •At least 18 years old, male or female
- •Subjects with locally advanced/metastatic solid tumors confirmed by histology and/or cytology;
- •Subjects in Part 1 should have at least one tumor lesion evaluable by RECIST v1.1 criteria, and subjects in Part 2 should have at least one measurable tumor lesion by RECIST v1.1 (lesions that have received radiotherapy or other local treatments cannot be used as target lesions unless there is clear progression of the lesion)
- •Subjects with locally advanced/metastatic solid tumors who have failed standard treatment: Part 1: Subjects with solid tumors who have experienced disease progression during/after at least one previous standard systemic anti-tumor regimen and are not suitable for standard treatment. Part 2: Non-small cell lung cancer, liver cancer, head and neck squamous cell carcinoma, colorectal cancer that have experienced disease progression during/after at least one previous standard systemic anti-tumor regimen and are not suitable for standard treatment
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Expected survival period ≥ 12 weeks
- •Adequate organ and bone marrow function
- •Archived formalin-fixed, paraffin-embedded (FFPE) tumor tissue or fresh biopsy tissue within 5 years must be provided before the first administration
Exclusion Criteria
- •A history of active second primary malignancy within the past 2 years, except for localized tumors that are considered cured and have a low risk of recurrence as assessed by the investigator.
- •Symptomatic central nervous system (CNS) metastases occurring within 2 weeks prior to the first dose of study treatment; or requirement for local therapy (e.g., radiotherapy or surgery) for CNS metastases; or requirement for corticosteroid therapy for CNS metastases.
- •A history of non-infectious interstitial lung disease (ILD)/pulmonary inflammation requiring corticosteroid treatment; current ILD/pulmonary inflammation; or suspected ILD/pulmonary inflammation that cannot be ruled out by screening imaging.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites, or occurrence of such effusions requiring drainage or medical intervention within 4 weeks prior to the first dose of study treatment.
- •Failure to recover from adverse events (AEs) induced by prior anti-tumor therapy (i.e., recovery to Grade 1 or baseline level).
- •Current participation in a study involving investigational drugs or medical devices, or participation in such a study within 4 weeks prior to the first dose of study treatment.
- •Receipt of the following therapies prior to the first dose of study treatment:
- •Cytotoxic therapy within 3 weeks; or anti-tumor targeted small-molecule drugs (e.g., tyrosine kinase inhibitors) within 2 weeks.
- •Anti-tumor antibody-based immune checkpoint inhibitors, antibody-drug conjugates (ADCs), or other anti-tumor biologics within the shorter of 5 half-lives or 4 weeks.
- •Traditional Chinese medicines (TCMs)/herbal preparations with anti-tumor indications within 2 weeks.
Arms & Interventions
Dose escalation
SIM0610 administered intravenously at selected dose levels according to protocol
Intervention: SIM0610 for Injection (Drug)
Cohort expansion
SIM0610 administered intravenously at Recommended dosage(RDs) according to protocol
Intervention: SIM0610 for Injection (Drug)
Outcomes
Primary Outcomes
Dose Limiting Toxicity (DLT)
Time Frame: From time of first dose of SIM0610 to end of DLT period (approximately 21 days)
Safety and Tolerability
Time Frame: From time of Informed Consent to 28 days post last dose of SIM0610
Objective response rate (ORR)
Time Frame: From date of first dose of SIM0610 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)
Objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Secondary Outcomes
No secondary outcomes reported