A Phase I Trial of SIM1811-03 in Subjects With Advanced Tumors

An Open-label, Phase I Trial of SIM1811-03 to Assess the Safety, Efficacy and Pharmacokinetics/Pharmacodynamics in Subjects With Advanced Tumors

This is a first in human, open-label, dose escalation and expansion Phase I study of SIM1811-03 in adult patients with advanced tumors. SIM1811-03 is a first-in-class IgG1-based humanized anti-tumor necrosis factor type 2 receptor (TNFR2) monoclonal antibody for the treatment of malignant tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; Cutaneous T Cell Lymphoma
• Intervention / Treatment: Drug: SIM1811-03 or in combination with Sintilimab injectiont

Detailed Description

This is a phase I trial to evaluate the safety, efficacy, and pharmacokinetic/ pharmacodynamic characteristics of SIM1811-03 in participants with advanced tumors.

The trial is composed of two parts, Part I and Part II. Part I is a dose escalation part to determine the MTD and/or RD of SIM1811-03 or SIM1811-03 in combination with Sintilimab Injection . Part II is a dose expansion part at RD level SIM1811-03 determined in Part I to assess the anti-tumor activity of SIM1811-03 or SIM1811-03 in combination with Sintilimab Injection in participants with advanced solid tumors or CTCL. The tumor types in Part II will be adjusted based on the response observed in Part I.

• Study Type: Interventional
• Enrollment (Estimated): 255
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jiongyan Li, MD; Phone Number: 86(25)8556 6666; Email: lijiongyan@zaiming.com
• Study Contact Backup: Name: Jing Wang; Email: wangjing16f919@zaiming.com

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Ruihua Xu, MD; Phone Number: 86-20-8734-3468; Email: xurh@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Written informed consent must be obtained prior to any procedures that are not considered standard of care.
2. ≥18 years old on the day of signing informed consent, male or female;
3. Histologically and/or cytologically documented advanced/metastatic solid tumors or histologically confirmed CTCL;
4. Have relapsed or refractory advanced solid tumors or CTCL, whose disease has progressed during or after standard therapy
5. At least one measurable tumor lesion (RECIST 1.1) for participants with solid tumors. Tumor lesions previously treated with radiotherapy or local therapy should not be considered as measurable unless progression is documented.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
7. Life expectancy of ≥ 12 weeks.
8. Adequate organ and marrow functions 9） Provide archived or fresh biopsy tumor tissue samples or tissue sections

10) Females of childbearing potential require strict contraception during the study.

Exclusion Criteria:

1) Participated in an interventional clinical trial or has used investigational devices within 28 days prior to first dose of study drug or received systemic anti-cancer treatments.

2）Toxicity due to previous antineoplastic therapy has not recovered to grade 0 or 1 unless such AEs are not considered to pose safety risks.

3) Required use of corticosteroids for more than 7 consecutive days within 14 days prior to the first dose of study treatment.

4) Participated with active or history of or risk of autoimmune disease 5) Major surgery (except biopsy) or unhealed wound within 4 weeks prior to first dose of study drug.

6) Other known malignancies within 2 years prior to enrollment. 7) Has known active central nervous system (CNS) metastases. 8) History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, symptomatic interstitial lung disease or evidence of active pneumonia that is not considered appropriate by the investigator.

9) Participants with a history of active pulmonary tuberculosis infection within 1 year prior to first dose of study drug.

10) History of hemorrhagic disease requiring transfusion within the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SIM1811-03 monotherapy or SIM1811-03 in combination with Sintilimab injection; All participants receive SIM1811-03 or SIM1811-03 in combination with Sintilimab injection	Drug: SIM1811-03 or in combination with Sintilimab injectiont; SIM1811-03 is a first-in-class igG-1 based humanized anti-tumor necrosis factor type 2 receptor (TNFR2) monoclonal antibody for the treatment of malignant tumor. Sintilimab is an IgG4 humanized monoclonal antibody against programmed cell death protein 1 (PD-1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part I The maximum tolerated dose (MTD) or recommended dose (RD)	Part I (dose escalation): To estimate the maximum tolerated dose (MTD) or recommended dose (RD) of SIM1811-03 Monotherapy or in combination with sintilimab	Within 28 days after the first dose in Q2W; Within 21 days after the first dose in Q3W
Part II ORR for Solid Tumor	Solid tumors: objective response rate (ORR) assessed by Investigator per RECIST 1.1 from baseline to disease progression	Q2W: Participants will be evaluated every 8 weeks from baseline to Treatment Cycle 12 (an average of 1 year); Q3W:Participants will be evaluated every 6 weeks from baseline to Treatment Cycle 12 (an average of 1 year)
Part II ORR for CTCL	CTCL: ORR assessed by Investigator per global response score	Q2W:Participants will be evaluated every 8 weeks from baseline to Treatment Cycle 12 (an average of 1 year); Q3W:Participants will be evaluated every 6 weeks from baseline to Treatment Cycle 12 (an average of 1 year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability (incidence of AE and SAE)	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)	All AEs/SAEs will be collected in this study from the time the subject signs the informed consent form until 90 days after the last dose
Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab	Serum concentrations of study drugs	from Cycle 1 to Last dose (an average of 1 year)
Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab	Area under the concentration-time curve (AUC)	from Cycle 1 to Last dose (an average of 1 year)
Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab	Maximum concentration (Cmax)	from Cycle 1 to Last dose (an average of 1 year)
Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab	Pre-dose (trough) concentration (Ctrough)	from Cycle 1 to Last dose (an average of 1 year)
Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab	Time to maximum concentration (Tmax)	from Cycle 1 to Last dose (an average of 1 year)
Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab	Half-life (T1/2)	Collection point would Predose, 0 hour, 24 hours, 168hours, 336 hours post-dose from Cycle 1 to Last dose (an average of 1 year)
Antidrug antibodies of SIM1811-03 and Sintilimab	Incidence of serum antidrug antibodies.	before staring the treatment for the first 7 treatment cycles (each cycle would be 28 days/21 days)
Neutralizing antibodies of SIM1811-03 and Sintilimab	Incidence of neutralizing antibodies to study drugs.	before staring the treatment for the first 7 treatment cycles (each cycle would be 28 days/21 days)

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Biologics Co., Ltd
• Investigators: Principal Investigator: Ruihua Xu, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2022
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: January 31, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 23, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous
• Other Study ID Numbers: SIM1811-03-TNFR2-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No