Clinical trial NCT05781360: A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0237 in Adult Participants with Advanced Solid Tumors
Official title: A Phase I First-in-human, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0237 in Adult Participants with Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Locally Advanced Unresectable or Metastatic Solid Tumor
Lead sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Xianxiang Medical Technology Co., Ltd.
name: Simcere Zaiming
First posted: 2023-03-23
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Dose Escalation (Part One): Incidence and nature of Dose-Limiting Toxicity (DLT)
timeFrame: 18 months
measure: Dose Escalation (Part One): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
timeFrame: 18 months
measure: Dose Escalation (Part One): Percentage of participants experiencing AE related dose interruptions and dose delays, dose intensity
timeFrame: 18 months
measure: Dose Expansion (Part Two): Objective Response Rate (ORR)
timeFrame: 12 months
Secondary outcomes:
measure: Dose Expansion (Part Two): Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
timeFrame: 18 months
measure: Dose Expansion (Part Two): Percentage of participants experiencing AE related dose interruptions and dose delays, dose intensity
timeFrame: 18 months
measure: Dose Escalation and Expansion: Assessment of SIM0237 Cmax
timeFrame: 30 months
measure: Dose Escalation and Expansion: Assessment of SIM0237 AUC
timeFrame: 30 months
measure: Dose Escalation and Expansion: Assessment of SIM0237 T1/2
timeFrame: 30 months
measure: Dose Escalation and Expansion: Assessment of SIM0237 antibody (ADA)
timeFrame: 30 months
measure: Dose Escalation (Part One): Objective Response Rate (ORR)
timeFrame: 48 months
measure: Dose Escalation and Expansion: Duration Of Response (DOR) assessed by investigator per RECIST Version 1.1
timeFrame: 48 months
measure: Dose Escalation and Expansion: Disease Control Rate (DCR) assessed by investigator per RECIST Version 1.1
timeFrame: 48 months
measure: Dose Escalation and Expansion: Progression-Free Survival (PFS) assessed by investigator per RECIST Version 1.1
timeFrame: 48 months
measure: Dose Escalation and Expansion: Time-To-Progression (TTP) assessed by investigator per RECIST Version 1.1
timeFrame: 48 months
measure: Dose Escalation and Expansion: Overall Survival (OS)
timeFrame: 48 months
measure: Dose Escalation and Expansion: ORR in participants with different PD-LI expression levels
timeFrame: 48 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Comprehensive Cancer Center
state: Indiana
city: New York
country: United States
facility: NYU Langone
state: New York
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Simcere Zaiming
name: Bijoyesh Mookerjee, MD
role: STUDY_CHAIR
References: