Trial Title:
GH55 for Advanced Cancers With MAPK Mutations: A Study on Safety and Early Results
NCT ID:
NCT06310382
Condition:
Advanced Solid Tumors With MAPK Signal Pathway Mutations
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
GH55
Description:
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.
Arm group label:
GH55 GROUP
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.
Detailed description:
This study is divided into two parts, namely the dose escalation phase I study and the
dose expansion phase II study. This study plans to include 5 dose groups, namely 40 mg,
80 mg, 150 mg, 200 mg, and 250 mg, and adopts a "3+3" dose escalation design. All of the
40 mg, 80 mg, 150 mg, 200 mg and 250 mg groups will adopt the "3+3" design, and 3-6
subjects will be enrolled in each group. The enrollment of the first subject and
subsequent subject in each dose group should be at least 7 days apart.
Subjects will receive a single dose of GH55 on day 1 (Cycle 0 Day 1, C0D1). The
investigator will assess the safety data on day 3 (C0D3) to determine whether subjects
can be initiated on multiple doses of GH55 [quaque die (QD) continuously, and 3 weeks per
cycle] on day 4 (C1D1). The dose limiting toxicity (DLT) observation period is from the
initiation of single dosing to the end of the first cycle of multiple dosing [Cycle 0 (3
days) and Cycle 1 (3 weeks)]. The sponsor and investigator will jointly assess the safety
data to determine whether to ascend to the next higher dose. These steps will be repeated
until MTD is reached, and the safety, tolerability, and PK profile of single dose and
multiple doses of oral administration of GH55 will be assessed. If MTD cannot be
determined when the dose escalation study is complete, the sponsor and investigator will
jointly determine whether to increase the ascending dose based on the existing safety,
tolerability, PK, PD and preliminary efficacy data. All subjects can continue the
treatment until disease progression, initiation of new antitumor treatment, withdrawal of
informed consent, or death (whichever occurs first). The dose expansion phase II study
will begin once the last subject in the dose escalation phase I study has completed the
DLT observation. Two dose expansion groups will be designed, with a dose level in each
group that is expected to become the RP2D based on the safety, tolerability, PK/PD
profile, and preliminary efficacy data of GH55 in the dose escalation phase I study. Two
dose expansion groups will enroll 60-80 subjects to further evaluate the efficacy,
safety, and PK/PD profile of GH55 in patients with advanced solid tumors.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Subjects must meet all the following inclusion criteria to be qualified for study
enrollment:
1. Male or female subjects aged 18-80 years (inclusive).
2. Patients with histologically or cytologically confirmed MAPK mutant (presence of
RAS/RAF/MEK/ERK mutations) locally advanced or metastatic solid tumors.
3. Patients who have failed standard treatment or have no standard treatment regimen or
are not suitable for standard treatment currently.
4. 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).
5. Eastern Cooperative Oncology Group (ECOG) performance status score: Phase I dose
escalation: 0-1. Phase II dose expansion: 0-2.
6. 3 months or longer expected survival.
7. 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.
8. Subjects must give informed consent to the study and voluntarily signed the informed
consent form prior to study initiation.
Exclusion Criteria:
Subjects who meet any one of the following exclusion criteria are not eligible for study
enrollment:
1. 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.
2. Received other unmarketed clinical investigational drug or therapy within 4 weeks
prior to the first dose.
3. 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.
4. Use of strong CYP3A4 inhibitors or inducers within 1 week prior to the first dose of
the investigational drug.
5. Previously received other selective ERK inhibitors.
6. Previously received allogeneic HSCT or organ transplantation.
7. 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).
8. Brain parenchymal metastasis or meningeal metastasis with clinical symptoms
unsuitable for study participation as judged by the investigator.
9. Patient with active infection and currently requires intravenous anti-infective
therapy.
10. History of immunodeficiency, including being positive for HIV antibody test.
11. 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).
12. History of severe cardiovascular and cerebrovascular diseases, including but not
limited to:
- Severe abnormalities in cardiac rhythm or conduction, such as ventricular
arrhythmia or second- or third-degree atrioventricular block requiring clinical
intervention;
- Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or
other grade 3 or greater cardiovascular and cerebrovascular events within 6
months prior to the first dose;
- New York Heart Disease Association (NYHA) class ≥ III cardiac function or left
ventricular ejection fraction (LVEF) < 50%;
- Clinically uncontrolled hypertension;
- Any factors that increase the risk of QTc prolongation or arrhythmia, such as
heart failure, hypokalemia that is difficult to correct, congenital long QT
syndrome, family history of long QT syndrome, and use of concomitant medication
known to prolong QT interval.
13. History of other malignant tumors (except for the cured squamous cell carcinoma in
situ of the skin, basal cell carcinoma, and cervical carcinoma in situ that have not
recurred within 5 years and are considered acceptable for study enrollment by the
investigator; except for patients who are considered acceptable for enrollment by
the investigator in the dose escalation study).
14. History of retinal vein occlusion or central serous retinopathy, or patients with
clinically significant abnormalities in the ophthalmological examination during the
screening period and judged by the investigator to be unsuitable for enrollment.
15. Unable to swallow medication or has conditions that severely impact gastrointestinal
absorption (e.g. Chronic diarrhea or intestinal obstruction) as judged by the
investigator.
16. Clinically uncontrolled third space effusion judged by the investigator to be
unsuitable for enrollment.
17. Patients with current interstitial lung disease (except radiation-induced pulmonary
fibrosis that does not required hormone therapy).
18. Known alcohol or drug dependence.
19. Mental disorder or poor compliance.
20. Previous history of severe allergy, or allergy to any active or non-active
ingredients of the investigational drug.
21. Pregnant or lactating women.
22. Other conditions judged by the investigator that render the subject unsuitable for
participation.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai East Hospital
Address:
City:
Shanghai
Zip:
200120
Country:
China
Status:
Recruiting
Contact:
Last name:
JIN LI, DOCTORATE
Phone:
021-38804518
Email:
lijin@csco.org.cn
Start date:
December 7, 2022
Completion date:
August 4, 2025
Lead sponsor:
Agency:
Suzhou Genhouse Bio Co., Ltd.
Agency class:
Other
Collaborator:
Agency:
Shanghai East Hospital
Agency class:
Other
Collaborator:
Agency:
Shandong Tumor Hospital
Agency class:
Other
Source:
Suzhou Genhouse Bio Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06310382