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

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05781386
• Collaborator: (none)
• Enrollment: 120
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 45.8
• Patients Per Site Per Month: 2.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor; Cutaneous T Cell Lymphoma	Drug: SIM1811-03	Phase 1

Detailed Description

This is a phase I trial to evaluate the safety, efficacy, and pharmacokinetic/ pharmacodynamic characteristics of SIM1811-03 in subjects 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. Approximately70 subjects will be enrolled in this part. 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 in subjects with advanced solid tumors or CTCL. The tumor types in Part II will be adjusted based on the response observed in Part I. Approximately 50 subjects will be enrolled in this part.

Part I: Dose escalation part (5 Dose Levels planned for Q2W dosing and 2 Dose Levels planned for Q3W dosing.)

Part II:

Cohort 1: Patients with CTCL (approximately 20 subjects) Cohort 2: Patients with advanced/metastatic solid tumors, including ovarian cancer, NSCLC, and hepatocellular carcinoma etc. (approximately 30 subjects)

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Phase I Trial of SIM1811-03 to Assess the Safety, Efficacy and Pharmacokinetics/Pharmacodynamics in Subjects With Advanced Tumors
• Actual Study Start Date: Mar 6, 2022
• Anticipated Primary Completion Date: Jun 30, 2025
• Anticipated Study Completion Date: Dec 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SIM1811-03 monotherapy All participants receive SIM1811-03 alone	Drug: SIM1811-03; 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; Other Names: SIM0235

Outcome Measures

Primary Outcome Measures

1. Part I The maximum tolerated dose (MTD) or recommended dose (RD) [Within 28 days after the first dose]

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

2. Part II ORR for Solid Tumor [Patients will be evaluated every 8 weeks from baseline to Treatment Cycle 12 (an average of 1 year]

   Solid tumors: objective response rate (ORR) assessed by Investigator per RECIST 1.1 from baseline to disease progression

3. Part II ORR for CTCL [Patients will be evaluated every 8 weeks from baseline to Treatment Cycle 12 (an average of 1 year)]

   CTCL: ORR assessed by Investigator per global response (Olsen 2011)

Secondary Outcome Measures

1. 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]

   Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

2. Pharmacokinetic of SIM1811-03 [from Cycle 1 to Last dose (an average of 1 year)]

   Serum concentrations of SIM1811-03 over time

3. Pharmacokinetic of SIM1811-03 [from Cycle 1 to Last dose (an average of 1 year)]

   Area under the concentration-time curve (AUC)

4. Pharmacokinetic of SIM1811-03 [from Cycle 1 to Last dose (an average of 1 year)]

   Maximum concentration (Cmax)

5. Pharmacokinetic of SIM1811-03 [from Cycle 1 to Last dose (an average of 1 year)]

   Pre-dose (trough) concentration (Ctrough)

6. Pharmacokinetic of SIM1811-03 [from Cycle 1 to Last dose (an average of 1 year)]

   Time to maximum concentration (Tmax)

7. Pharmacokinetic of SIM1811-03 [Collection point would Predose, 0 hour, 24 hours, 168hours, 336 hours post-dose from Cycle 1 to Last dose (an average of 1 year)]

   Half-life (T1/2) Time to maximum concentration (Tmax) Half-life (T1/2)

8. anti-SIM1811-03 antibodies [before staring the treatment for the first 7 treatment cycles (each cycle would be 28 days)]

   Titer of serum anti-SIM1811-03 antibodies

9. anti-SIM1811-03 antibodies [before staring the treatment for the first 7 treatment cycles (each cycle would be 28 days)]

   Incidence of serum anti-SIM1811-03 antibodies

10. SIM1811-03 Anti-tumor activity [before staring the treatment for the first 7 treatment cycles (each cycle would be 28 days)]

    Incience of neutralizing antibodies to SIM1811-03 Anti-tumor activity of SIM1811-03

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 patients 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. 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. Patients with active or history of or risk of autoimmune disease

3. Major surgery (except biopsy) or unhealed wound within 4 weeks prior to first dose of study drug

4. Has known active central nervous system (CNS) metastases

5. 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.

6. Subjects with a history of active pulmonary tuberculosis infection with 1 year of first dose of study drug

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

8. Known psychiatric disorder or drug abuse that would interfere the trial requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sun Yat-Sen University Cancer Center	Guanzhou	Guangdong	China

Sponsors and Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.

Investigators

• Principal Investigator: Ruihua Xu, MD, Sun Yat-sen University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jiangsu Simcere Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05781386
• Other Study ID Numbers: SIM1811-03-TNFR2-101
• First Posted: Mar 23, 2023
• Last Update Posted: Mar 23, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Lymphoma, T-Cell, Cutaneous

Study Results

No Results Posted as of Mar 23, 2023