A Study to Evaluate Safety, PK and Efficacy of GH55 in Combination With GH21 in Patients With Solid Tumors

Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Efficacy of GH55 Capsule in Combination With GH21 Capsule in Subjects With Locally Advanced or Metastatic Solid Tumors Harboring Aberrantly Activated MAPK Signaling Pathway.

GH55 Capsule is a novel, highly selective small molecule dual mechanism ERK1/2 inhibitor. GH21 Capsule is a potent, orally active human SHP2 allosteric inhibitor. The combination of an ERK1/2 inhibitor and an SHP2 inhibitor achieves a dual effect: synergistic upstream and downstream blockade of the aberrantly activated RTK MAPK signaling pathway, as well as complementation of resistance mechanisms.

This study will evaluate the safety, tolerability and pharmacokinetic (PK) characteristics of GH55 Capsule in combination with GH21 Capsule in patients with advanced solid tumors with aberrantly activated MAPK signaling pathway, and investigate the efficacy of this combination regimen in the same patient population.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor Cancer
• Intervention / Treatment: Drug: Phase I dose escalation; Drug: Phase I: Dose Expansion; Drug: phase II

• Study Type: Interventional
• Enrollment (Estimated): 152
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: SHIYA CHEN, BACHELOR; Phone Number: +8615618310761; Email: chenshiya@genhousebio.com
• Study Contact Backup: Name: QIAN DONG, MASTER; Phone Number: +8615221908116; Email: dongqian@genhousebio.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Shanghai Goboard Cancer Hospital
      • Contact: JIN LI, DOCTORATE; Phone Number: +8613761222111; Email: lijin@csco.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Aged 18-80 years (inclusive), regardless of gender.
• 2. Histologically or cytologically confirmed locally advanced or metastatic solid tumor with aberrantly activated MAPK signaling pathway (RAS/RAF/MEK/ERK).
• 3. Failed standard treatment, has no standard treatment options, refuses standard treatment, or is not eligible for standard treatment at the current stage.
• 4. Has at least one measurable tumor lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• 6. Estimated survival time ≥ 3 months.

• 7. Essential organ function is basically normal, with screening laboratory results meeting the following criteria:

  • Hematological system (no blood transfusion or hematopoietic stimulants within 14 days)
  • Absolute Neutrophil Count (ANC) ≥1.5×109/L
  • Platelet (PLT) ≥75×109/L
  • Hemoglobin (Hb) ≥90g/L
  • Liver function
  • Albumin (ALB) ≥3.0g/dL
  • Total Bilirubin (TBIL) ≤1.5×Upper Limit of Normal (ULN);
    For patients with --Gilbert syndrome: ≤3×ULN
  • Alanine Aminotransferase (ALT) ≤2.5×ULN;
    For patients with liver metastasis or liver cancer: ≤5×ULN
  • Aspartate Aminotransferase (AST) ≤2.5×ULN;
    For patients with liver metastasis or liver cancer: ≤5×ULN
  • Renal function
  • Creatinine (Cr) ≤1.5×ULN
  • Creatinine Clearance (Ccr) ≥50ml/min (calculated by 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%
  • Fridericia-corrected QT interval (QTcF) Male<450ms; Female<470ms
• 8. Eligible patients of childbearing potential (male and female) must agree to use reliable contraceptive methods (hormonal, barrier, or abstinence) with their partners during the trial and for at least 3 months after the last dose; female patients of childbearing potential must have a negative serum pregnancy test within 1 week before the first dose.
• 9. Must understand the study requirements, voluntarily sign a written informed consent form before the trial.

Exclusion Criteria:

• 1. Received chemotherapy within 3 weeks, or radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, or other anti-tumor treatments within 4 weeks before the first dose, except:
• - Nitrosourea or mitomycin C: within 6 weeks before the first dose;
• - Oral fluoropyrimidines, small-molecule targeted drugs, or traditional Chinese medicine with anti-tumor indications: within 2 weeks before the first dose;
• - Local palliative radiotherapy: within 2 weeks before the first dose.
• 2. Received other unmarketed clinical research drugs or treatments within 4 weeks before the first dose.
• 3. Underwent major organ surgery (excluding needle biopsy) or suffered significant trauma within 4 weeks before the first dose.
• 4. Used strong inhibitors or inducers of CYP3A4 or P-gp within 1 week before the first dose.
• 5. Previously received other selective ERK inhibitors and/or SHP2 inhibitors.
• 6. Previously received hematopoietic stem cell transplantation or organ transplantation.
• 7. Adverse reactions from previous anti-tumor treatment have not recovered to NCI CTCAE v5.0 Grade ≤ 1 (except for toxicities judged by investigators to be safe, such as alopecia, Grade 2 peripheral neuropathy, or hypothyroidism stabilized with hormone replacement therapy).
• 8. Symptomatic parenchymal brain metastasis or meningeal metastasis, deemed unsuitable for enrollment by investigators.
• 9. Has an active infection requiring intravenous anti-infective treatment.
• 10. Has a history of immunodeficiency, including positive HIV antibody test.
• 11. Active hepatitis B (HBsAg positive and HBV-DNA > 500 IU/ml, 1000 cps/ml, or the study center's lower limit of detection [if higher]); antiviral therapy (excluding interferon) is allowed. Active hepatitis C (patients with positive HCV antibody but HCV-RNA < the study center's lower limit of detection are eligible).
• 12. Has a history of severe cardiovascular and cerebrovascular diseases, including but not limited to:
• - Severe cardiac arrhythmia or conduction abnormalities requiring clinical intervention (e.g., ventricular arrhythmia, third-degree atrioventricular block);
• - Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade ≥ 3 cardiovascular and cerebrovascular events within 6 months before the first dose;
• - New York Heart Association (NYHA) cardiac function class ≥ III;
• - Clinically uncontrolled hypertension;
• - Any factors increasing the risk of QTc prolongation or arrhythmia (e.g., heart failure, intractable hypokalemia, congenital long QT syndrome, family history of long QT syndrome, use of any known drugs that prolong the QT interval [see Appendix 8]).
• 13. Has a history of other malignant tumors (except cured in situ cancers with no recurrence for 5 years, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, as deemed eligible by investigators; eligible in the dose escalation phase at the discretion of investigators).
• 14. Has a history of retinal vein occlusion or central serous chorioretinopathy.
• 15. Unable to swallow oral medications, or has conditions severely affecting gastrointestinal absorption (e.g., chronic diarrhea, intestinal obstruction) as judged by investigators.
• 16. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently).
• 17. Has a history of interstitial pneumonia within 6 months before the first dose, or any evidence of clinically active interstitial lung disease.
• 18. Has aberrantly activated PI3K-mTOR pathway (including PI3K activating mutations, AKT activating mutations, and PTEN deletion or inactivation).
• 19. Has known alcohol or drug dependence.
• 20. Has a mental disorder or poor compliance.
• 21. Has a history of severe allergies or allergies to multiple drugs.
• 22. Is pregnant or lactating.
• 23. Deemed unsuitable for the study by investigators for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: GH55 Capsule in combination with GH21 Capsule

Drug: Phase I dose escalation; Drug: GH55 Drug: GH21 Treatment Group: Subjects will receive oral GH55 and GH21 following a dose-escalation design until confirmed disease progression, unacceptable toxicity, or fulfillment of any study withdrawal criterion.; Drug: Phase I: Dose Expansion; Drug: GH55 Drug: GH21 Treatment Group: Subjects will receive oral GH55 and GH21 at two dose levels established in the Dose Escalation phase until confirmed disease progression, unacceptable toxicity, or fulfillment of any study withdrawal criterion.; Drug: phase II; Drug: GH55 Drug: GH21 Treatment Group: Subjects will receive oral GH55 and GH21 at the fixed dose established during the Phase I portion until confirmed disease progression, unacceptable toxicity, or fulfillment of any study withdrawal criterion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ia: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (according to NCI CTCAE 5.0).	Evaluated at each dose level GH55 and GH21, as graded by National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 5.0.	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia: Dose Limited Toxicity (DLT)	Evaluated at each dose level GH55 and GH21, as graded by National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 5.0.	28 Days (first cycle)
Phase Ib and Phase II: Progression-Free Survival (PFS)	Antitumor activity was evaluated by assessing tumor response using RECIST 1.1 criteria.	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ib and Phase II: Objective response rate (ORR)	The number (%) of patients with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by investigator.	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics	Area under the concentration-time curve (AUC) from time 0 to time of last concentration measured and from time 0 extrapolated to infinity and from time 0 to time of the dosing interval at steady state	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ib and Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (according to NCI CTCAE 5.0).	Graded by National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 5.0.	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics	Maximum plasma concentration	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics	Time to maximum observed concentration	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics	Terminal half-life	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics	Apparent clearance and apparent volume of distribution	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics	Mean residence time	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics	Trough concentration at steady state	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics	Maximum concentration at steady state	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics	Accumulation ratio	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Duration of Response (DOR)	Antitumor activity was evaluated by assessing tumor response using RECIST 1.1 criteria.	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia, Phase Ib and Phase II: Disease Control Rate (DCR)	Antitumor activity was evaluated by assessing tumor response using RECIST 1.1 criteria.	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.
Phase Ia: Progression-Free Survival (PFS)	Antitumor activity was evaluated by assessing tumor response using RECIST 1.1 criteria.	From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.

Collaborators and Investigators

• Sponsor: Suzhou Genhouse Bio Co., Ltd.
• Collaborators: Shanghai Goboard Cancer Hospital
• Investigators: Principal Investigator: JIN LI, DOCTORATE, Shanghai Goboard Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 24, 2026
• Primary Completion (Estimated): October 30, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Epidemiologic Study Characteristics; Clinical Trials as Topic; Clinical Studies as Topic; Clinical Trials, Phase II as Topic
• Other Study ID Numbers: GH55C201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No