GH55 for Advanced Cancers With MAPK Mutations: A Study on Safety and Early Results

NCT06310382 | Recruiting Phase 1 FDA Drug

• 1 other identifier: GH55-CRS001
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, open-label, dose escalation phase I and dose expansion phase II study aimed to evaluate the safety, tolerability, PK and PD profiles as well as to observe the efficacy of GH55 in patients with MAPK mutant advanced solid tumors. This study is divided into two parts, namely the dose escalation phase I study and the dose expansion phase II study.

Conditions

Advanced Solid Tumors With MAPK Signal Pathway Mutations

Outcome Measures

Primary Outcomes (3)

• Dose-limiting Toxicities Incidence Count Among Study Participants

  Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle. (phase I)

  2 years

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

  All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments (phase I)

  2 years

• Response Rate (ORR) Based on RECIST 1.1 Criteria

  ORR is defined as the proportion of participants with complete response or partial response (CR+PR). (phase II)

  2 years

Secondary Outcomes (6)

• Progression-free survival (PFS) Based on RECIST 1.1 Criteria

  2 years

• Duration of response (DOR) Based on RECIST 1.1 Criteria

  2 years

• Number of participants with adverse events

  2 years

• Plasma concentration (Cmax)

  2 years

• Time to achieve Cmax (Tmax)

  2 years

Study Arms (1)

GH55 GROUP

EXPERIMENTAL

Drug: GH55

Interventions

GH55 DRUG

GH55 capsule is a novel small molecule, highly selective dual-mechanism ERK1/2 inhibitor developed by Suzhou Genhouse Bio. Co., Ltd. This product can be used to treat cancers caused by abnormal activation of the MAPK pathway (mutational activation of RAS/RAF/MEK) by targeted inhibition of ERK1/2.

GH55 GROUP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18-80 years (inclusive).
• Patients with histologically or cytologically confirmed MAPK mutant (presence of RAS/RAF/MEK/ERK mutations) locally advanced or metastatic solid tumors.
• Patients who have failed standard treatment or have no standard treatment regimen or are not suitable for standard treatment currently.
• Dose escalation: At least one assessable tumor lesion according to RECIST version 1.1; Dose expansion: At least one measurable tumor lesion according to RECIST version 1.1 (tumor lesion located in the region of previous radiotherapy or other locoregional treatment sites is usually not considered a measurable lesion, unless this lesion shows clear progression or persists for 3 months after radiotherapy).
• Eastern Cooperative Oncology Group (ECOG) performance status score: Phase I dose escalation: 0-1. Phase II dose expansion: 0-2.
• months or longer expected survival.
• Major organs are functioning normally, and laboratory tests meet the following criteria during the screening period.
• Hematological system (has not received any blood transfusion or hematopoietic stimulating factor therapy within the past 14 days) Absolute neutrophil count (ANC) ≥ 1.5 × 109/L Platelet Count (PLT) ≥ 75 × 109/L Hemoglobin (Hb) ≥ 90 g/L Liver function Albumin (ALB) ≥ 3.0 g/dL Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN) Liver metastasis or liver cancer patients: ≤ 2.5 × ULN Alanine Aminotransferase (ALT) ≤ 2.5 × ULN; Liver metastasis or liver cancer patients: ≤ 5 × ULN Aspartate aminotransferase (AST) ≤ 2.5 × ULN; Liver metastasis or liver cancer patients: ≤ 5 × ULN Renal function Creatinine clearance rate (Ccr) ≥ 60 mL/min (calculated based on the Cockcroft-Gault formula) Coagulation function Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN International normalized ratio (INR) ≤ 1.5 × ULN Cardiac function Left ventricular ejection fraction (LVEF) ≥ 50% QT interval corrected by the Fridericia formula (QTcF) Males \< 450 ms, Females \< 470 ms 7. Qualified patients (male and female) with childbearing potential must agree to use reliable contraceptives (hormone or barrier or abstinence) with their partners during the study and until at least 3 months after the last dose; female patients with childbearing potential must be negative for the blood pregnancy test within 1 week before the first dose.
• \. Subjects must give informed consent to the study and voluntarily signed the informed consent form prior to study initiation.

You may not qualify if:

• Received antitumor therapy such as chemotherapy within 3 weeks before the first dose, radiotherapy, biotherapy, endocrine therapy, targeted therapy, and immunotherapy within 4 weeks before the first dose, except for the following:
• Use of nitrosoureas or mitomycin C within 6 weeks prior to the first dose of the investigational drug;
• Use of oral fluorouracil(s), small molecule targeted drugs, and antitumor traditional Chinese medicine within 2 weeks prior to the first dose of the investigational drug;
• Local palliative radiotherapy within 2 weeks prior to the first dose of the investigational drug.
• Received other unmarketed clinical investigational drug or therapy within 4 weeks prior to the first dose.
• Underwent major organ surgery (excluding needle biopsy) or had significant trauma within 4 weeks prior to the first dose or requires selective surgery during the study period.
• Use of strong CYP3A4 inhibitors or inducers within 1 week prior to the first dose of the investigational drug.
• Previously received other selective ERK inhibitors.
• Previously received allogeneic HSCT or organ transplantation.
• Adverse drug reactions of previous antitumor treatment have not recovered to grade ≤ 1 as per CTCAE version 5.0 (except for toxicity without safety risk judged by the investigator, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism that is stable after hormone replacement therapy).
• Brain parenchymal metastasis or meningeal metastasis with clinical symptoms unsuitable for study participation as judged by the investigator.
• Patient with active infection and currently requires intravenous anti-infective therapy.
• History of immunodeficiency, including being positive for HIV antibody test.
• Active hepatitis B \[HBsAg positive and HBV-DNA \> 500 IU/mL or LLQ of the study site (when the LLQ is \> 500 IU/mL)\], for which antiviral therapies other than interferon are permitted; Active hepatitis C (patients who are positive for HCV antibody but whose HCV-RNA is \< study site LLQ can be included).
• History of severe cardiovascular and cerebrovascular diseases, including but not limited to:

Sponsors & Collaborators

• Suzhou Genhouse Bio Co., Ltd.: lead
• Shanghai East Hospital: collaborator
• Shandong Tumor Hospital: collaborator

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

RECRUITING

Study Officials

• JIN LI, DPCTORATE

  021-38804518

  PRINCIPAL INVESTIGATOR

• HAIDAN WANG, DOCTORATE

  0512-86861608

  STUDY DIRECTOR

Central Study Contacts

YIMING ZHOU, bachelor

CONTACT

0512-86861608; zhouyiming@genhousebio.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 7, 2024
• First Posted: March 15, 2024
• Study Start: December 7, 2022
• Primary Completion: May 26, 2025
• Study Completion: August 4, 2025
• Last Updated: July 8, 2024

Record last verified: 2024-07

Locations

CN (1)