A Phase I First-in-Human Study of GenSci128 in Patients With Solid Tumors Harboring a TP53 Y220C Mutation

A Phase I, Multicenter, Multinational, Open-label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of GenSci128 Tablet in Patients With Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation

The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of GenSci128 Tablet in Patients with Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation

Study Overview

• Status: Recruiting
• Conditions: Solid Tumors Harboring a TP53 Y220C Mutation
• Intervention / Treatment: Drug: GenSci128 tablets

• Study Type: Interventional
• Enrollment (Estimated): 82
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wen Xu; Phone Number: +8618861095711; Email: xuwen01@genscigroup.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Zhongshan Hospital ,Fudan University
      • Contact: Tianshu Liu, Doctor; Phone Number: +8613681973996
      • Contact: liu.tianshu@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has the ability to understand and the willingness to sign a written informed consent document (prior to the initiation dose of GenSci128 and any study procedures)
2. Is willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures
3. Has confirmed TP53 Y220C mutation in tumor tissue
4. Has histologically or cytologically confirmed locally advanced or metastatic solid tumors and have progressed following standard therapy, or for whom, in the opinion of the investigator, no available and effective standard therapy exists.
5. Has at least one measurable lesion by RECIST v1.1
6. Has an ECOG status of 0 or 1
7. Has a life expectancy of ≥ 3 months.

Exclusion Criteria:

1. Has diagnosed as primary central nervous system (CNS) tumor.
2. Has CNS metastases, unless asymptomatic, neurologically stable and not requiring steroids treatment for at least 2 weeks prior to initiation dose of GenSci128.
3. Has a history of leptomeningeal disease or spinal cord compression.
4. Has stroke or transient ischemic attack within 6 months prior to initiation dose of GenSci128.
5. Has active infection requiring intravenous (IV) antibiotics or other uncontrolled inter-current illness requiring hospitalization. Minor infections, e.g., periodontal infection or urinary tract infection (UTI), which may be treated with short term oral antibiotics are allowed.
6. Uncontrolled hypertension (Blood pressure ≥ 150/90 mmHg despite optimal medical management)
7. Has a history of prior organ transplant or allogeneic stem cell transplant.
8. Has received a selective reactivator of p53 Y220C mutation.
9. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence ≤ 14 days after intervention).
10. Has known human immunodeficiency virus (HIV) infection (positive HIV 1/2 antibodies) or known chronic hepatitis B or C [participants positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA; participants positive for hepatitis C virus (HCV) IgG will be eligible if they are negative for HCV-RNA].
11. Is persisting toxicity related to prior anticancer therapy (NCI CTCAE V5.0 Grade>1). However, alopecia and sensory neuropathy Grade ≤2, or other Grade ≤2 adverse events not constituting a safety risk, based on the investigator's judgment are acceptable.
12. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or GenSci128 administration or may interfere with the interpretation of study results, in the judgment of the investigator, would make the participant inappropriate for entry into this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 150mg dose level	Drug: GenSci128 tablets; GenSci128 tablets have three specifications, including 50mg, 200mg, 500mg, and are taken in combination with the doctor's advice in different dose levels. GenSci128 will be orally administrated daily (except single dose in Cycle 0) with no interruptions until occurrence of unacceptable toxicity, or progressive disease, or withdrawal of consent, or death, or contact lost, or starting a new anticancer therapy, etc. (whichever occurs first).
Experimental: 300mg dose level	Drug: GenSci128 tablets; GenSci128 tablets have three specifications, including 50mg, 200mg, 500mg, and are taken in combination with the doctor's advice in different dose levels. GenSci128 will be orally administrated daily (except single dose in Cycle 0) with no interruptions until occurrence of unacceptable toxicity, or progressive disease, or withdrawal of consent, or death, or contact lost, or starting a new anticancer therapy, etc. (whichever occurs first).
Experimental: 600mg dose level	Drug: GenSci128 tablets; GenSci128 tablets have three specifications, including 50mg, 200mg, 500mg, and are taken in combination with the doctor's advice in different dose levels. GenSci128 will be orally administrated daily (except single dose in Cycle 0) with no interruptions until occurrence of unacceptable toxicity, or progressive disease, or withdrawal of consent, or death, or contact lost, or starting a new anticancer therapy, etc. (whichever occurs first).
Experimental: 1200mg dose level	Drug: GenSci128 tablets; GenSci128 tablets have three specifications, including 50mg, 200mg, 500mg, and are taken in combination with the doctor's advice in different dose levels. GenSci128 will be orally administrated daily (except single dose in Cycle 0) with no interruptions until occurrence of unacceptable toxicity, or progressive disease, or withdrawal of consent, or death, or contact lost, or starting a new anticancer therapy, etc. (whichever occurs first).
Experimental: 1800mg dose level	Drug: GenSci128 tablets; GenSci128 tablets have three specifications, including 50mg, 200mg, 500mg, and are taken in combination with the doctor's advice in different dose levels. GenSci128 will be orally administrated daily (except single dose in Cycle 0) with no interruptions until occurrence of unacceptable toxicity, or progressive disease, or withdrawal of consent, or death, or contact lost, or starting a new anticancer therapy, etc. (whichever occurs first).
Experimental: 2500mg dose level	Drug: GenSci128 tablets; GenSci128 tablets have three specifications, including 50mg, 200mg, 500mg, and are taken in combination with the doctor's advice in different dose levels. GenSci128 will be orally administrated daily (except single dose in Cycle 0) with no interruptions until occurrence of unacceptable toxicity, or progressive disease, or withdrawal of consent, or death, or contact lost, or starting a new anticancer therapy, etc. (whichever occurs first).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AEs) and dose limiting toxicities (DLTs)	Part 1 is a dose escalation study ，to assess the safety and tolerability of GenSci128 in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation	3 weeks
maximal tolerance dose （MTD）、recommended dose of expansion （RDE）	Part 1 is a dose escalation study ，to determine the maximum tolerated dose (MTD), if any, and recommend dose of expansion (RDE) for GenSci128 in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation	up to 3 months
recommended phase 2 dose （RP2D）	Part 2 is a dose expansion study，Determining Recommended Phase II Dose	up to 3 months

Collaborators and Investigators

• Sponsor: Changchun GeneScience Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: March 19, 2025
• First Submitted That Met QC Criteria: March 26, 2025
• First Posted (Actual): April 3, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GenSci128-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No