Histologically or Cytologically Confirmed Advanced Solid Tumors
Conditions
Brief summary
an open-label, multicenter, Phase I study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) characteristics of SIM0532 in participants with advanced solid tumors. The study commences with a dose-escalation part (Part 1), followed by a dose-expansion part (Part 2).
Detailed description
Part 1 will be guided by the Bayesian Optimal Interval (BOIN) dose-escalation rule. In Part 2, patients with advanced pancreatic adenocarcinoma, RAS-mutant advanced non-small cell lung cancer (NSCLC) and other RAS-mutant advanced solid tumors.
Interventions
DRUGSIM0532 Tablets
SIM0532 Tablets
Sponsors
Jiangsu Simcere Pharmaceutical Co., Ltd.
Shanghai Xianwei Medical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Signed the informed consent form prior to performing the specified procedures required by the study. * 2\. Aged ≥18 years. * 3\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. * 4\. Expected survival ≥12 weeks. * 5\. Laboratory test results indicating sufficient organ function. * 6\. At least one measurable lesion per RECIST v1.1;
Exclusion criteria
* 1\. A history of other malignant tumors within 2 years. * 2\. With symptomatic central nervous system (CNS) metastases. * 3\. Gastrointestinal diseases that affect drug administration/absorption. * 4\. Known psychiatric disorders or substance abuse that may interfere with the conduct of the study. * 5\. Uncontrolled pleural effusion, pericardial effusion or ascites requiring drainage or medical intervention within 4 weeks. * 6\. Any active infection requiring systemic treatment within 2 weeks. * 7\. A history of non-infectious pneumonia requiring oral or intravenous steroid therapy for recovery, or interstitial lung disease (ILD) or severe obstructive pulmonary disease. * 8\. Previous treatment with RAS-targeting therapies other than RAS (OFF) inhibitors. * 9\. Failure to recover from adverse events (AEs) caused by previous antineoplastic therapy. * 10\. Currently participating in or having participated in a study of other investigational drugs or devices within 4 weeks. * 11\. Major surgery within 4 weeks. * 12\. Previous antineoplastic therapy before the first dose of study treatment should have a certain wash-out period * 13\. Vaccination with any live vaccine within 4 weeks. * 14\. Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). * 15\. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; * 16\. A history of clinically significant cardiovascular disease. * 17\. A history of allogeneic organ transplantation or graft-versus-host disease (GVHD). * 18\. Known hypersensitivity to the study drug or any of its excipients. * 19\. Participants who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) | From informed consent signing to 30 days after the last dose |
| Part 2: Incidence and severity of subjects with AEs/SAEs | From informed consent signing to 30 days after the last dose |
| Part 2: Objective response rate (ORR) | About 24 months. |
| Part 1: Dose-limiting toxicity (DLT) | Cycle 1 Day 1 (C1D1) to Cycle 1 Day 21 (C1D21) (Each cycle is 21 days) |
Secondary
| Measure | Time frame |
|---|---|
| Time to response (TTR) | About 24 months |
| Progression-free survival (PFS) | About 24 months |
| Overall survival (OS) | About 24 months |
| Maximum plasma concentration (Cmax) | About 24 months |
| Duration of response (DOR) | About 24 months |
| Disease control rate (DCR) | About 24 months |
Countries
China
Outcome results
None listed