Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Escalating Doses of SIM0348 as a Single Agent in Advanced Solid Tumors

Study Overview
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Brief Summary
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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 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).

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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SIM0348
* Drug: SIM0348


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 (dose escalation and dose expansion)<br>Cohorts of at least 3 participants each will be treated with escalating doses of SIM0348. Dose expansion part will be decided based on the findings of dose escalation part. | Drug: SIM0348<br>* 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.<br>|
| Experimental: Part 2 (cohort expansion)<br>Participants will be treated with SIM0348 at a recommended dose (RD) in the study. | Drug: SIM0348<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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