First-in-human GenSci128 treatment for solid tumors with the 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

This trial will test whether the oral drug GenSci128 is safe, well tolerated, and can help adults with advanced or metastatic solid tumors that have the TP53 Y220C mutation.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 82 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Changchun GeneScience Pharmaceutical Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06908434 on ClinicalTrials.gov

What this trial studies

This Phase I, first-in-human, open-label trial gives oral GenSci128 tablets to adults with locally advanced or metastatic solid tumors that carry the TP53 Y220C mutation. The study uses dose-escalation to define safety, tolerability, and pharmacokinetics and also collects preliminary tumor response data using RECIST v1.1. Eligible patients must have progressed on standard therapies, have at least one measurable lesion, and an ECOG performance status of 0–1. All treatment and follow-up visits occur at Zhongshan Hospital, Fudan University, with safety labs and imaging to monitor drug effects and adverse events.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed locally advanced or metastatic solid tumors that harbor the TP53 Y220C mutation, have progressed after standard therapy, have at least one measurable lesion, ECOG 0–1, and life expectancy ≥3 months.

Not a fit: Patients without the TP53 Y220C mutation, those with primary CNS tumors or unstable/symptomatic brain metastases, or patients with poor performance status or short expected survival are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, GenSci128 could provide a targeted oral therapy option for patients whose tumors carry the TP53 Y220C mutation and who have exhausted standard treatments.

How similar studies have performed: This is a first-in-human trial of GenSci128; while TP53-targeted approaches have shown promise in preclinical work, there are limited clinical data for therapies specifically targeting the Y220C mutation.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital ,Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Wen Xu

Conditions Solid Tumors Harboring a TP53 Y220C Mutation