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

NCT ID: NCT05781386

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 255 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-06
• Study Completion Date: 2025-12-30

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.

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.

Conditions

Advanced Solid Tumor; Cutaneous T Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: EXPERIMENTAL

SIM1811-03 or in combination with Sintilimab injectiont

Intervention Type: 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)

Interventions

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)

Intervention Type: DRUG

Eligibility Criteria

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.

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

Sponsors

Jiangsu Simcere Biologics Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ruihua Xu, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-Sen University Cancer Center

Guanzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jiongyan Li, MD

Role: CONTACT

lijiongyan@zaiming.com

86(25)8556 6666

Jing Wang

Role: CONTACT

wangjing16f919@zaiming.com

Facility Contacts

Ruihua Xu, MD

Role: primary

xurh@sysucc.org.cn

86-20-8734-3468

References

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.

Reference Type: DERIVED

PMID: 37589506 (View on PubMed)

Other Identifiers

SIM1811-03-TNFR2-101

Identifier Type: -

Identifier Source: org_study_id