Locally advanced or metastatic solid tumors carrying the TP53 Y220C mutation
Conditions
Interventions
Experimental group:Phase 1:
Accelerated titration design will be performed at dose level 1 and dose level 2 with within-subject dose escalation.
- If no grade >=2 TEAEs occur in the first subject duri
- If the first subject has a grade >=2 TEAEs during DLT observation at dose level 1, stop the within-subject dose escalation and initiate the BF-BOIN design from dose level 1.
?Stage 2: BF-BOIN design
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion 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.Age >=18 at time of signing ICF (or the legal age of consent if > 18 in the jurisdiction in which the study is taking place). 4.Has confirmed TP53 Y220C mutation in tumor tissue; 5.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. 6.Is able to provide fresh or archival tumor tissues (FFPE blocks or at least 10 unstained slides). These samples will be used to retrospectively identify TP53 Y220C and other gene (e.g., KRAS) mutations in the central laboratory; 7.Has at least one measurable lesion by RECIST v1.1. 8.Has an ECOG status of 0 or 1; 9.Has a life expectancy of >= 3 months. 10.Has adequate hematologic and organ function within 7 days prior to initiation dose of GenSci128, defined by the following; 11.WOCBP must be willing to use adequate contraception while receiving GenSci128, and within 30 days after the last dose of GenSci128 and have a negative serum or urine HCG test within 7 days prior to initiation dose of GenSci128. 12.Nonsterile males must be willing to use adequate contraception for the duration of receiving GenSci128 and within30 days after the last dose of GenSci128.
Exclusion criteria
Exclusion criteria: 1.Any active malignancy 470 msec obtained from 3 consecutive ECGs during screening period. e) With any factors that increase the risk of torsade de pointes (e.g., hypokalemia despite standard medical management, family history of long QT syndrome). f) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, second /third degree heart block). 9.Has a history of prior organ transplant or allogeneic stem cell transplant. 10.Has received a selective reactivator of p53 Y220C mutation. 11.Known severe hypersensitivity to GenSci128 and/or any of its excipients; 12.Has undergone major surgery within 4 weeks prior to initiation dose of GenSci128. 13.Has received treatment with any of the following anti-cancer therapies prior to initiation dose of GenSci128. a) Any herbal medicine or Chinese patent medicines treatment which have anti-cancer activity within 2 weeks. b) Radiotherapy within 4 weeks. c) Chemotherapy or hormonal therapy within 3 weeks. d) Biological therapy (e.g., cytokines or antibodies) or small molecule targeting drugs within 5 half-lives or 4 weeks (whichever is shorter). 14.Has received strong inducers or inhibitors of CYP3A4 or P-gp, or proton pump inhibitors, or medications with a known risk of QT/QTc prolongation within 5 half-lives or 14 days (whichever is longer) prior to initiation dose of GenSci128; 15.Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence = 14 days after intervention). 16.Has inability to swallow oral medications (i.e., tablets, capsules) without chewing, breaking, crushing, opening or otherwise altering the product formulation. 17.Has gastrointestinal illness that in the opinion of the investigator, would preclude the absorption of GenSci128, which is an oral agent; 18.Has known HIV infection (positive HIV 1/2 antibodies) or known chronic hepatitis B or C [participants positive for HBsAg or HBcAb will be eligible if they are negative for HBVDNA; participants
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tumor size; | — |
Countries
China
Contacts
Public ContactLiu Tianshu
Zhongshan Hospital, Fudan University
Outcome results
None listed