A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0237 in Adult Participants with Advanced Solid Tumors

NCT ID: NCT05781360

Last Updated: 2024-12-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-08
• Study Completion Date: 2024-05-25

Brief Summary

This is a multicenter, open-label, phase I study to evaluate the safety, efficacy, and pharmacokinetic (PK)/pharmacodynamic(PD) characteristics of SIM0237 in participants with advanced solid tumors.

Detailed Description

The study starts with a dose escalation part (Part 1) followed by a dose expansion part (Part 2). The main purpose of this study is to evaluate the safety and tolerability of SIM0237 and determine the maximum tolerated dose (MTD) (if any) and/or the recommended dose(s) (RD) and preliminary anti-tumor activity when given once every week or other dosing regimens. Additional purposes of the study are to evaluate the pharmacokinetics (PK) properties, immunogenicity, correlation of the biomarkers and PK profile with anti-tumor activity.

Conditions

Locally Advanced Unresectable or Metastatic Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental: PART ONE- Dose escalation

The purpose of the Dose Escalation Phase (Part one) is to characterize the safety and tolerability of SIM0237 and determine the maximum tolerated dose (MTD) (if any) and/or the recommended dose(s) (RD) based on the frequency of the occurrence of DLTs in each cohort during the DLT evaluation period.

Group Type: EXPERIMENTAL

SIM0237

Intervention Type: DRUG

SIM0237 should be administered intravenously at recommended dose qw or other dosing regimens

Experimental: PART TWO- Dose expansion

Patients will be administered a recommended dose of SIM0237 established from the Dose Escalation Phase of the study.

Group Type: EXPERIMENTAL

SIM0237

Intervention Type: DRUG

SIM0237 should be administered intravenously at recommended dose qw or other dosing regimens

Interventions

SIM0237

SIM0237 should be administered intravenously at recommended dose qw or other dosing regimens

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written informed consent;
• ≥18 years of age;
• Histological/cytological diagnosis of selected locally advanced unresectable or metastatic solid tumor not amenable to local therapies (clinical diagnosis of HCC is allowed); participants must have failed to derive clinical benefit on standard therapies, or ineligible for the standard of care therapy
• Presence of at least one measurable lesion according to RECIST Version 1.1
• ECOG performance status score of 0 or 1;
• Life expectancy of ≥12 weeks;
• Participant must have adequate main organ function.
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the start of study treatment. WOCBP must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from heterosexual activity throughout the study, starting from the first dose of the study treatment through 180 days after the last dose of study treatment.
• Male participants must agree to use adequate contraception starting from the first dose of the study treatment through 180 days after the last dose of the study treatment.

Exclusion Criteria

• Within the defined washout periods for prior anti-cancer treatments;
• Participant is currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of SIM0237.
• Any other malignancy within 2 years prior to the first dose of the study treatment except for localized cancers that are considered to have been cured and in the opinion of the Investigator present a low risk for recurrence.
• Participant has not recovered (i.e., to Grade 1 or to baseline) from previous anticancer therapy-induced AEs.
• Participants with a history of recently (within previous 2 years of the first dose of the study treatment) active diverticulitis or symptomatic peptic ulcer disease;
• Major surgery within 2 weeks of receiving the first dose of study treatment;
• Participant has symptomatic central nervous system (CNS) metastases, or CNS metastases requiring CNS-directed local therapy (such as radiotherapy or surgery) or corticosteroids therapy within 2 weeks of first dose of study treatment;
• Participants with a history of active pulmonary tuberculosis infection within 1 year; participants with history more than 1 year prior to the first dose of study treatment may be considered suitable if there is no evidence of active pulmonary tuberculosis judged by the Investigator;
• Participants with clinically significant cardiovascular diseases, in the past 6 months prior to the first dose of the study treatment; symptomatic coronary heart disease requiring drug treatment; arrhythmia requiring drug treatment; QTcF interval >480 msec; or uncontrolled hypertension;
• Participants who have ascites requiring drainage or pleural effusion or pericardial effusion requiring drainage within 28 days after previous drainage; Known human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS);
• Active or chronic hepatitis B or hepatitis C infection; participant with HBsAg positive or detective HBV-DNA at screening should receive antiviral treatment as per local practice during the study.
• Concomitant therapy with any other anti-cancer therapy or chronic use of immunosuppressive doses (more than 10 mg/day of prednisone or equivalent) of systemic corticosteroids.
• Active known or suspected autoimmune disease.
• History of non-infectious pneumonitis that has required a course of oral or intravenous steroids to assist with recovery, or interstitial lung disease or severe obstructive pulmonary disease;
• History of severe hypersensitivity reactions to mAbs;
• History of allogeneic organ transplantation or graft-versus-host disease;
• Use of any live vaccine therapy within 4 weeks prior to the first dose of study treatment;
• Any active infection requires systemic treatment via intravenous infusion within 2 weeks prior to the first dose of study treatment;
• Known psychiatric disorder or drug abuse that would interfere the trial requirements;
• Previous treatment with IL-15 agonists;
• Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
• Other conditions that researchers consider inappropriate for inclusion.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Xianxiang Medical Technology Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Simcere Zaiming

UNKNOWN

Sponsor Role: collaborator

Jiangsu Simcere Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bijoyesh Mookerjee, MD

Role: STUDY_CHAIR

Simcere Zaiming

Locations

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

NYU Langone

New York, New York, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Anhui Provincial Hospital

Hefei, Anhui, China

Fujian Cancer Hospital

Fuzhou, Fujian, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Hunan Cancer Hospital

Changsha, Hunan, China

Shandong Cancer Hospital

Jinan, Shandong, China

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Countries

United States; China

Other Identifiers

SIM0237-101

Identifier Type: -

Identifier Source: org_study_id