A Phase I Trial of SIM1811-03 in Subjects With Advanced Solid Tumors and Cutaneous T-cell Lymphoma

NCT05569057 | Unknown Phase 1 FDA Drug

• 1 other identifier: SIM1811-03-TNFR2-102
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 6

Brief Summary

This is a first in human, open-label, dose escalation and expansion Phase 1 study of SIM1811-03 in adult patients with advanced solid tumors and cutaneous T-cell lymphoma. 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 (CTCL)

Outcome Measures

Primary Outcomes (2)

• Phase 1a: Incidence Rate of Dose-Limiting Toxicity (DLT)

  To estimate the maximum tolerated dose (MTD) or recommended dose (RD) of SIM1811-03

  Within 28 days after the first dose

• Phase 1b: ORR Solid tumors: objective response rate (ORR) assessed by Investigator per RECIST 1.1 CTCL: ORR assessed by Investigator per global response (Olsen 2011)

  Phase 1b (dose expansion): To evaluate the anti-tumor activity of SIM1811-03 at the proposed RD

  Assessed up to an average of 1 year

Secondary Outcomes (14)

• Incidence and severity of adverse events (AEs)

  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

• Incidence of dose interruptions, delays and discontinuations

  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

• AUC

  Days 1, 2, 4, 8, and 15 of Cycle 1 (each cycle is 28 days), then assessed in subsequent cycles, up to an average of 1 year

• Cmax

  Days 1, 2, 4, 8, and 15 of Cycle 1 (each cycle is 28 days), then assessed in subsequent cycles, up to an average of 1 year

• Ctrough

  Days 1, 2, 4, 8, and 15 of Cycle 1 (each cycle is 28 days), then assessed in subsequent cycles, up to an average of 1 year

Study Arms (1)

SIM1811-03 Monotherapy

EXPERIMENTAL

All participants receive SIM1811-03 alone

Drug: SIM1811-03

Interventions

SIM1811-03 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 tumors

Also known as: SIM0235, TNFR2 monoclonal antibody

SIM1811-03 Monotherapy

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. Patients with lymphoma other than CTCL are not eligible.
• 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 patients with solid tumors. Tumor lesions previously treated with radiotherapy or local therapy should not be considered as measurable unless progression is documented.
• For patients with CTCL, the following criteria must be met:
• Have at least one measurable lesion (mSWAT criteria) , the lesion that has previously been treated with local therapy should not be considered as measurable unless progression is documented;
• Provide tissue from a punch biopsy of the skin at screening (except for patients in phase Ia dose escalation phase, for whom skin biopsies is recommended only).
• Mycosis fungoides (MF) or Sézary Syndrome (SS) (Stage IIb-IV based on Tumor Node Metastasis Blood \[TNMB\] staging system for SS and MF diagnosed at screening) failed of at least 2 prior systemic therapies
• Meet clinical criteria for systemic treatment (patients that can be treated with radiotherapy and/or skin-directly therapies only are to be excluded)
• No current large cell transformation
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Life expectancy of ≥ 12 weeks
• Adequate organ and marrow functions
• Provide archival tumor samples or fresh tumor biopsy (mandatory for Phase Ib, and recommended for Phase Ia)

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 any following systemic anti-cancer treatments:
• cytotoxic chemotherapy, targeted therapy, immune checkpoint inhibitor within 4 weeks (such as PD-1 inhibitor, PD-L1 inhibitor, or CTLA-4 inhibitor);
• radiotherapy within 2 weeks (palliative radiotherapy is allowed at least 1 week before the study drug treatment).
• Toxicity and side effects (due to previous anticancer treatments) have not recovered to ≤ grade 1, unless such AE is not considered to pose safety risks (such as hair loss and neuropathy ≤ grade 2 caused by chemotherapy).
• Required use of corticosteroids for more than 7 consecutive days within 14 days prior to the first dose of study treatment (\> 10 mg daily prednisone equivalent for solid tumors; \> 20 mg daily prednisone equivalent for CTCL)
• Patients with active or history of or risk of autoimmune disease
• Major surgery (except biopsy) or unhealed wound within 4 weeks prior to first dose of study drug
• Any other current or previous malignancy within the past 2 years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, c) carcinoma in situ of the breast d) local prostate cancer after radical resection and/ or definitive radiotherapy with stable prostate specific antigen (PSA) levels for 1 years
• Has known active central nervous system (CNS) metastases
• 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
• History of immunodeficiency (including HIV infection)
• Known active hepatitis B or C infection
• Patients with clinically significant cardiovascular diseases
• History of severe allergic reaction to the study drug or excipients used in the protocol
• Has had an allogeneic tissue/solid organ transplant or graft-versus-host disease

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead

Study Sites (6)

Henry Ford Health

Detroit, Michigan, 48202, United States

NOT YET RECRUITING

NYU Lagone Health

New York, New York, 10016, United States

NOT YET RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

NOT YET RECRUITING

Carolina Biooncology Institute

Huntersville, North Carolina, 28078, United States

RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

NOT YET RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

NOT YET RECRUITING

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

Central Study Contacts

Bijoyesh Mookerjee, M.D.

CONTACT

856-261-0153; bijoyesh.mookerjee@simceregroup.com

Adam Cox

CONTACT

905-486-0339; Adam.Cox@allucent.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: September 27, 2022
• First Posted: October 6, 2022
• Study Start: September 30, 2022
• Primary Completion: June 1, 2024
• Study Completion: March 31, 2025
• Last Updated: October 7, 2022

Record last verified: 2022-10

Locations

US (6)