Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0348 in Advanced Solid Tumors

A Phase I, First-in-Human, Open-Label Study to Investigate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of SIM0348 in Subjects With Advanced Solid Tumors

This is a multicenter, open label, phase I trial to evaluate the safety and tolerability, pharmacokinetic/ pharmacodynamic characteristics and to assess the preliminary efficacy of SIM0348 as monotherapy or with sintilimab in adult subjects with advanced and metastatic solid tumors. The trial starts with a dose escalation and dose expansion part (Part 1) followed by a cohort expansion part (Part 2).

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: SIM0348; Drug: SIM0348 + Sintilimab

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults 18 years of age or older
• Must have failed at least one established standard anti-cancer therapies
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy at least 12 weeks
• Adequate hematologic and end organ function
• Histologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for which standard therapy has proven ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care
• Confirmed availability of representative tumor specimens
• Measurable disease according to RECIST Version 1.1

Exclusion Criteria:

• Malignancies other than disease under study within 2 years prior to Day 1 of Cycle 1
• Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases
• History of interstitial lung disease, evidence of active pneumonitis (history of radiation pneumonitis in the radiation field [fibrosis] is permitted), and active pneumonia that are considered inappropriate by the investigator
• History of severe hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• History of autoimmune disease
• Positive human immunodeficiency virus (HIV) test
• Severe infection within 2 weeks prior to the first dose of study treatment
• Significant cardiovascular disease
• History of allogeneic tissue/solid organ transplant or graft-versus-host disease
• Known clinically significant liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A ( SIM0348 Monotherapy); Part 1A (dose escalation and dose expansion) Cohorts of at least 3 participants each will be treated with escalating doses of SIM0348 alone or in combination with Sintilimab . Dose expansion part will be decided based on the findings of dose escalation part. Part 1A was to evaluate single agent SIM0348 once weekly or once every 3 weeks.	Drug: SIM0348; Several dose levels will be evaluated for SIM0348 administered as a single agent . SIM0348 will be given via IV infusion on Day 1, Day 8, Day 15, Day 22 of each cycle (28-day or depending on study cohort and phase) until disease progression or loss of clinical benefit.
Experimental: Part 1B (SIM0348 + Sintilimab ); Part 1B (dose escalation and dose expansion) Cohorts of at least 3 participants each will be treated with escalating doses of SIM0348 alone or in combination with Sintilimab. Dose expansion part will be decided based on the findings of dose escalation part. In Part 1B, selected dose from Part 1A were evaluated in Part 1B when they were combined with Sintilimab (200mg once every 3 weeks)	Drug: SIM0348 + Sintilimab; Selected doses from Part 1A will be evaluated for SIM0348 when they were combined with Sintilimab (200mg once every 3 weeks).
Experimental: Part 2A (SIM0348 Monotherapy Cohort Expansion); Selected doses from Part 1A will be evaluated for SIM0348 administered as a single agent. SIM0348 will be given via IV infusion until disease progression or loss of clinical benefit.	Drug: SIM0348; Several dose levels will be evaluated for SIM0348 administered as a single agent . SIM0348 will be given via IV infusion on Day 1, Day 8, Day 15, Day 22 of each cycle (28-day or depending on study cohort and phase) until disease progression or loss of clinical benefit.
Experimental: Part 2B (SIM0348 + Sintilimab Cohort Expansion); Selected doses from Part 1B will be evaluated for SIM0348 when they were combined with Sintilimab (200mg once every 3 weeks)	Drug: SIM0348 + Sintilimab; Selected doses from Part 1A will be evaluated for SIM0348 when they were combined with Sintilimab (200mg once every 3 weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Dose-limiting toxicity (DLT)		DLT evaluation window was from Baseline to the end of Cycle 1 (up to 28 days)
Part 2: Objective response rate (ORR) assessed by Investigator per RECIST v.1.1	To evaluate the anti-tumor activity of SIM0348 alone and in combination with Sintilimab	up to approximately 2 years

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2026

Study Registration Dates

• First Submitted: January 29, 2023
• First Submitted That Met QC Criteria: February 6, 2023
• First Posted (Actual): February 8, 2023

Study Record Updates

• Last Update Posted (Actual): August 25, 2026
• Last Update Submitted That Met QC Criteria: August 21, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; sintilimab
• Other Study ID Numbers: SIM0348-101

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