A Phase Ia/Ib Study of GH2616 Tablet in Subjects With Advanced Solid Tumors

NCT06329206 | Recruiting Phase 1 FDA Drug

• 1 other identifier: GH2616-101
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ia/Ib, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, pharmacodynamics (PD) and preliminary efficacy of GH2616 Tablet in subjects with advanced solid tumors. It includes two parts: the dose escalation study (Phase Ia) and the dose expansion study (Phase Ib).

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Number of Participants Reporting Adverse Events (AEs) or Serious Adverse Events (SAEs)

  Adverse events (AE), serious adverse events (SAE), and severity of AE using the NCI-CTCAE version 5.0.

  2 years

• Dose-limiting Toxicities Incidence Count Among Study Participant

  DLT refers to Dose-Limiting Toxicity. It is defined as a side effect or adverse reaction of a drug or treatment that is severe enough to prevent an increase in dosage. Identifying DLT is crucial in clinical trials for determining the maximum tolerated dose (MTD) of a new drug.

  2 years

Secondary Outcomes (7)

• Objective Response Rate (ORR) based on RECIST 1.1 criteria

  2 years

• Progression-Free Survival (PFS) based on RECIST 1.1 criteria

  2 years

• Duration of Response (DOR) based on RECIST 1.1 criteria

  2 years

• Plasma Concentration (Cmax)

  2 years

• Area Under the plasma Concentration-Time Curve (AUC)

  2 years

Study Arms (1)

GH2616 GROUP

EXPERIMENTAL

Dose Escalation: Dose Escalation Cohorts Subjects will be enrolled at various doses of GH2616. These Dose Escalation Cohorts will be utilized to To determine the maximum tolerated dose (MTD) and/or recommended dose for expansion(s) (RDEs) for Dose Expansion. Dose Escalation: Backfill Cohorts 2 \~ 3 dose cohorts are allowed to be backfilled.These Backfill Cohorts will be utilized to build additional data to support selection of doses and/or tumor types for further study in Dose Expansion. Dose Expansion: Expansion Cohorts 2 \~ 3 dose cohorts are planned.Subjects with advanced solid tumors harboring TP53 mutation and whole genome duplication (WGD+) will be enrolled.These Cohorts will be utilized to to determine the recommended Phase II dose (RP2D) of GH2616 Tablet.

Drug: GH2616 Tablets

Interventions

GH2616 Tablets DRUG

GH2616 tablets will be given orally

GH2616 GROUP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women ≥18 years old.
• The following two points are evaluated by the Investigator and are deemed suitable to participate in the study: a. The subject fully understands the requirements of the study and voluntarily signs the written informed consent; b. Be able to comply with the medication requirements of the study and all study related procedures and evaluations.
• Meeting the requirements of tumor types shown below:
• Phase Ia Study:
• Subjects with a histological or cytological diagnosis of recurrent or metastatic advanced solid tumors who have failed or are intolerant to standard treatment, or have no standard therapy. The specific tumor types include but not limited to high-grade serous ovarian cancer (HGSOC), uterine carcinosarcoma (UCS), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), triple-negative breast cancer (TNBC), bladder urothelial carcinoma (BLCA), colorectal cancer (CRC), etc.
• Phase Ib study:
• Dose expansion study (Phase Ib): Subjects with a histological or cytological diagnosis of recurrent or metastatic advanced solid tumors harboring TP53 mutation and WGD+ who have failed or are intolerant to standard treatment, or have no standard therapy.
• The specific tumor types include but not limited to high-grade serous ovarian cancer (HGSOC), uterine carcinosarcoma (UCS), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), triple-negative breast cancer (TNBC), bladder urothelial carcinoma (BLCA), colorectal cancer (CRC), etc.. Note: The specific tumor types/basket design with specific gene(s) will be determined by the principal Investigator and the Sponsor based on the Phase Ia study results.
• Survival expectations are ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (Appendix 1).
• Subjects with advanced solid tumors have at least one evaluable lesion according to RECIST 1.1 (Appendix 2).
• Subjects with adequate organ function at the time of screening (requiring no blood transfusion, no use of hematopoietic stimulating factor or human albumin within 14 days prior to screening), specifically defined as:
• Blood routine: Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count (PLT) ≥100×109/L; Hemoglobin (HGB) ≥ 90 g/L (9 g/dL);
• Liver function: Serum Total bilirubin (TBIL) ≤ 1.5 Upper limit of normal value (ULN), and serum TBIL≤ 3×ULN in patients with liver metastasis or confirmed Gilbert syndrome. Alanine aminotransferase (ALT) and Aspartate transferase (AST) ≤ 2.5×ULN in subjects without liver metastasis; ALT or AST≤ 5×ULN in subjects with liver metastasis;
• Renal function: estimated creatinine clearance (CLcr) ≥ 60 mL/min as calculated using Cockcroft-Gault formula (Appendix 3);

You may not qualify if:

• In Phase Ia and Ib studies, subjects will be excluded if they meet any of the following criteria:
• Has received chemotherapy within 21 days prior to the first administration of GH2616 Tablet or has received radiation therapy, biologic therapy, endocrine therapy, targeted therapy, immunotherapy, or other anti-tumor drug treatments within 28 days prior to the first administration of GH2616 Tablet, or other anti-tumor drugs or treatments within the following interval before the first administration of GH2616 Tablet: Nitrosoureas or mitomycin C within 6 weeks prior to the first administration of the investigational drug. Oral fluoropyrimidines, small molecule targeted therapies, and Chinese herbal medicines with indications for anti-tumor within 14 days prior to the first administration of the investigational drug. Local palliative radiation therapy within 14 days prior to the first administration of the investigational drug.
• Has received other investigational drugs or treatments not yet approved for marketing within 28 days prior to the first administration.
• At rest, the average Corrected QT interval (QTc, Fridericia's correction formula used) obtained by 12-lead Electrocardiograph (ECG) examination is \> 450 ms for males or 470 ms for females (confirmed by repeated examinations). A variety of clinically significant arrhythmia, conduction, and resting ECG abnormalities, such as complete left bundle branch block, degree III, degree II, PR interval \>250 ms. Various factors that may increase the risk of prolonged QTc or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of long QT syndrome in a direct family member or sudden unexplained death before age 40, and use of any medications known to prolong QT intervals.
• Has evidence of infectious diseases:
• Active hepatitis B (hepatitis B surface antigen (HbsAg) positive and hepatitis B virus deoxyribonucleic acid (HBV-DNA) \> 500 IU/ml or 1000 cps/ml or lower limit of detection at the study site \[only if lower limit of detection at the study site is higher than 500 IU/ml or 1000 cps/ml\]), antiviral therapy other than interferon is allowed; active hepatitis C (subjects with hepatitis C virus (HCV) antibody positive but hepatitis C virus ribonucleic acid (HCVRNA) \< lower limit of detection at the study site are allowed to be enrolled);
• HIV infected patients (HIV 1/2 antibody positive detected by antigen/antibody test); Considering that HIV infections can be chronically managed, expanding cancer clinical trial eligibility to be more inclusive of patients with HIV infections is justified in many cases, and may accelerate the development of effective therapies in cancer patients with these chronic infections. Therefore, well-controlled HIV patients who have been on established antiretroviral therapy (ART) for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment should be included. Note: patients who are using ART drugs that are prohibited or cautious concomitant medications specified in the protocol (e.g. strong inhibitors or strong inducers of P-gp) could be switched to an alternate effective ART regimen (with minimal drug-drug interaction potential) before study participation or should be excluded from the study if their regimen cannot be altered.
• Known active syphilis infection.
• Has symptomatic or active central nervous system (CNS) metastases. Treated or untreated asymptomatic patients with CNS lesions are eligible only if all of the following criteria are met:
• Presence of measurable lesions outside the CNS as determined by RECIST 1.1.
• No history of intracranial or spinal hemorrhage.
• No stereotactic radiation therapy or whole brain radiation therapy or neurosurgical resection within 28 days prior to initiation of study treatment.
• No continuous use of corticosteroids during CNS disease treatment period.
• Metastases limited to the cerebellum or supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
• No evidence of intermediate progression between completion of CNSdirected therapy (if given) and initiation of study treatment.

Sponsors & Collaborators

• Suzhou Genhouse Bio Co., Ltd.: lead
• Zhejiang Cancer Hospital: collaborator
• Henan Cancer Hospital: collaborator
• Hubei Cancer Hospital: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator

Study Sites (1)

Zhejiang Cancer Hospital

Zhejiang, China

RECRUITING

Central Study Contacts

SHIYA CHEN, bachelor

CONTACT

+8615618310761; chenshiya@genhousebio.com

ZHENGBO SONG, Doctorate

CONTACT

+8613857153345; zjccgcp_phase1@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2024
• First Posted: March 25, 2024
• Study Start: March 20, 2024
• Primary Completion: April 25, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 8, 2024

Record last verified: 2024-07

Locations

CN (1)