Advanced Solid Tumors With MAPK Signal Pathway MutationsPhase 1/2NCT06310382
GH55 for Advanced Cancers With MAPK Mutations: A Study on Safety and Early Results
A Phase 1/2 study testing GH55 in people with Advanced Solid Tumors With MAPK Signal Pathway Mutations, run by Suzhou Genhouse Bio Co., Ltd. at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Advanced Solid Tumors With MAPK Signal Pathway Mutations
- What is being tested?
- GH55
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteChina
- Study dates
- 7 Dec 2022to 4 Aug 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet all the following inclusion criteria to be qualified for study enrollment:
- 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.
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- 3 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.
- 8. Subjects must give informed consent to the study and voluntarily signed the informed consent form prior to study initiation.
Who cannot join
- Subjects who meet any one of the following exclusion criteria are not eligible for study enrollment:
- 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.
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- 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:
- 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.
- 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).
- 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.
- Unable to swallow medication or has conditions that severely impact gastrointestinal absorption (e.g. Chronic diarrhea or intestinal obstruction) as judged by the investigator.
- Clinically uncontrolled third space effusion judged by the investigator to be unsuitable for enrollment.
- Patients with current interstitial lung disease (except radiation-induced pulmonary fibrosis that does not required hormone therapy).
- Known alcohol or drug dependence.
- Mental disorder or poor compliance.
- Previous history of severe allergy, or allergy to any active or non-active ingredients of the investigational drug.
- Pregnant or lactating women.
- Other conditions judged by the investigator that render the subject unsuitable for participation.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai East Hospital
Shanghai, Shanghai Municipality, 200120
JIN LI, DOCTORATE, 021-38804518, lijin@csco.org.cn
About this study
Official title: A Phase I/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Antitumor Activity of GH55 in Patients Harboring MAPK Pathway Mutations in Advanced Solid Tumors
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.
Read the 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.
- Being tested
- GH55
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GH55Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| GH55 GROUP | Experimental | Not described Receives: Drug: GH55 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: 2 years
Secondary outcomes (6)
Progression-free survival (PFS) Based on RECIST 1.1 Criteria
PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression or death which occurs first. (phase I/II)
Measured: 2 years
Duration of response (DOR) Based on RECIST 1.1 Criteria
DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD). (phase I/II)
Measured: 2 years
Number of participants with adverse events
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 II)
Measured: 2 years
Plasma concentration (Cmax)
Highest observed plasma concentration of GH55. (phase I/II)
Measured: 2 years
Time to achieve Cmax (Tmax)
Time of highest observed plasma concentration of GH55. (phase I/II)
Measured: 2 years
Area under the plasma concentration-time curve (AUC)
Area under the plasma concentration time curve of GH55. (phase I/II)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2024
- Study start7 Dec 2022
- Primary completion26 May 2025 (estimated)
- Study completion4 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid Tumors With MAPK Signal Pathway MutationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Suzhou Genhouse Bio Co., Ltd.
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai East Hospital, Shandong Tumor Hospital
- Responsible party
- Sponsor
- Investigators
- JIN LI, DPCTORATE, Principal investigator, 021-38804518HAIDAN WANG, DOCTORATE, Study director, 0512-86861608
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06310382
- Sponsor's protocol ID
- GH55-CRS001
- Status last verified
- Jul 2024
- First submitted
- 7 Mar 2024
- Last updated
- 8 Jul 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Antitumor Activity of GH55 in Patients Harboring MAPK Pathway Mutations in Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT06310382
- Acronym / sponsor ID
- GH55-CRS001
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Suzhou Genhouse Bio Co., Ltd.University, hospital or other
- Collaborators
- Shanghai East Hospital, Shandong Tumor Hospital
- Study start
- 7 Dec 2022 (actual)
- Primary completion
- 26 May 2025 (estimated)
- Study completion
- 4 Aug 2025 (estimated)
- First posted
- 15 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GH55 GROUP | Experimental | Drug: GH55 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subjects must meet all the following inclusion criteria to be qualified for study enrollment:
- 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).
Key exclusion criteria (31 listed)
- Subjects who meet any one of the following exclusion criteria are not eligible for study enrollment:
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GH55GH55 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. | Drug | GH55 GROUP |
Primary outcome
Dose-limiting Toxicities Incidence Count Among Study Participants
Time frame: 2 years
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)
Number of Participants Reporting Adverse Events (AEs) or Serious Adverse Events (SAEs)Objective
Time frame: 2 years
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)
Response Rate (ORR) Based on RECIST 1.1 Criteria
Time frame: 2 years
ORR is defined as the proportion of participants with complete response or partial response (CR+PR). (phase II)
6 secondary outcomes
Progression-free survival (PFS) Based on RECIST 1.1 Criteria
Time frame: 2 years
Duration of response (DOR) Based on RECIST 1.1 Criteria
Time frame: 2 years
Number of participants with adverse events
Time frame: 2 years
Plasma concentration (Cmax)
Time frame: 2 years
Time to achieve Cmax (Tmax)
Time frame: 2 years
Area under the plasma concentration-time curve (AUC)
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2024.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
JIN LI, DPCTORATE principal investigator
021-38804518
HAIDAN WANG, DOCTORATE study director
0512-86861608
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing GH55 in people with Advanced Solid Tumors With MAPK Signal Pathway Mutations, run by Suzhou Genhouse Bio Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact YIMING ZHOU, bachelor (0512-86861608, zhouyiming@genhousebio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting Toxicities Incidence Count Among Study Participants (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2024; AzTrials last refreshed its copy on 27 Oct 2026.