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

NCT05781386 | Unknown Phase 1

• 1 other identifier: SIM1811-03-TNFR2-101
• Study Type: interventional
• Target: 255
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumor; Cutaneous T Cell Lymphoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (9)

• safety and tolerability (incidence of AE and SAE)

  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

  from Cycle 1 to Last dose (an average of 1 year)

• Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab

  from Cycle 1 to Last dose (an average of 1 year)

• Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab

  from Cycle 1 to Last dose (an average of 1 year)

• Pharmacokinetics profile of SIM1811-03 and in combination with Sintilimab

  from Cycle 1 to Last dose (an average of 1 year)

Study Arms (1)

SIM1811-03 monotherapy or SIM1811-03 in combination with Sintilimab injection

EXPERIMENTAL

All participants receive SIM1811-03 or SIM1811-03 in combination with Sintilimab injection

Drug: SIM1811-03 or in combination with Sintilimab injectiont

Interventions

SIM1811-03 or in combination with Sintilimab injectiont DRUG

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)

SIM1811-03 monotherapy or SIM1811-03 in combination with Sintilimab injection

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 must be obtained prior to any procedures that are not considered standard of care.
• ≥18 years old on the day of signing informed consent, male or female;
• Histologically and/or cytologically documented advanced/metastatic solid tumors or histologically confirmed CTCL;
• Have relapsed or refractory advanced solid tumors or CTCL, whose disease has progressed during or after standard therapy
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Life expectancy of ≥ 12 weeks.
• Adequate organ and marrow functions 9） Provide archived or fresh biopsy tumor tissue samples or tissue sections
• \) Females of childbearing potential require strict contraception during the study.

You may not qualify if:

• \) 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.
• ）Toxicity due to previous antineoplastic therapy has not recovered to grade 0 or 1 unless such AEs are not considered to pose safety risks.
• \) Required use of corticosteroids for more than 7 consecutive days within 14 days prior to the first dose of study treatment.
• \) 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.
• \) 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.
• \) Participants with a history of active pulmonary tuberculosis infection within 1 year prior to first dose of study drug.
• \) History of hemorrhagic disease requiring transfusion within the last 3 months.

Sponsors & Collaborators

• Jiangsu Simcere Biologics Co., Ltd: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guanzhou, Guangdong, China

RECRUITING

Related Publications (1)

• Gao Z, Zhang Q, Chen H, Chen J, Kang J, Yu H, Song Y, Zhang X. TNFR2 promotes pancreatic cancer proliferation, migration, and invasion via the NF-kappaB signaling pathway. Aging (Albany NY). 2023 Aug 16;15(16):8013-8025. doi: 10.18632/aging.204941. Epub 2023 Aug 16.

  PMID: 37589506 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ruihua Xu, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiongyan Li, MD

CONTACT

86(25)8556 6666; lijiongyan@zaiming.com

Jing Wang

CONTACT

wangjing16f919@zaiming.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2023
• First Posted: March 23, 2023
• Study Start: March 6, 2022
• Primary Completion: June 30, 2025
• Study Completion: December 30, 2025
• Last Updated: September 21, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)