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

NCT05781360 | Terminated Phase 1 FDA Drug

• 1 other identifier: SIM0237-101
• Study Type: interventional
• Target: 192
• Locations: 2 countries
• Sites: 9

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.

Conditions

Locally Advanced Unresectable or Metastatic Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Dose Escalation (Part One): Incidence and nature of Dose-Limiting Toxicity (DLT)

  DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for Cytokine Release Syndrome (CRS).

  18 months

• Dose Escalation (Part One): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)

  Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading

  18 months

• Dose Escalation (Part One): Percentage of participants experiencing AE related dose interruptions and dose delays, dose intensity

  Occurrence of AE related dose interruptions, dose delays and dose intensity (duration of SIM0237 exposure).

  18 months

• Dose Expansion (Part Two): Objective Response Rate (ORR)

  Proportion of participants who have a confirmed Complete Response (CR) or a Partial Response (PR), as the Best Overall Response (BOR) determined by Investigator per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  12 months

Secondary Outcomes (13)

• Dose Expansion (Part Two): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)

  18 months

• Dose Expansion (Part Two): Percentage of participants experiencing AE related dose interruptions and dose delays, dose intensity

  18 months

• Dose Escalation and Expansion: Assessment of SIM0237 Cmax

  30 months

• Dose Escalation and Expansion: Assessment of SIM0237 AUC

  30 months

• Dose Escalation and Expansion: Assessment of SIM0237 T1/2

  30 months

Study Arms (2)

Experimental: PART ONE- Dose escalation

EXPERIMENTAL

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.

Drug: SIM0237

Experimental: PART TWO- Dose expansion

EXPERIMENTAL

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

Drug: SIM0237

Interventions

SIM0237 DRUG

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

Experimental: PART ONE- Dose escalation; Experimental: PART TWO- Dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead
• Shanghai Xianxiang Medical Technology Co., Ltd.: collaborator
• Simcere Zaiming: collaborator

Study Sites (9)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

NYU Langone

New York, New York, 10016, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Anhui Provincial Hospital

Hefei, Anhui, 230061, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

Location

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

Location

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

Location

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bijoyesh Mookerjee, MD

  Simcere Zaiming

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2023
• First Posted: March 23, 2023
• Study Start: March 8, 2023
• Primary Completion: May 25, 2024
• Study Completion: May 25, 2024
• Last Updated: December 20, 2024

Record last verified: 2024-12

Locations

CN (6); US (3)