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

NCT07446725 | Not Yet Recruiting Phase 1

• 1 other identifier: GH55C201
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Solid Tumor Cancer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (13)

• Phase Ia, Phase Ib and Phase II: Evaluation of pharmacokinetics

  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).

  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

  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

  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

  From the initiation of study treatment to the completion of safety follow-up after the end of study treatment. Approximately 2 years.

Study Arms (1)

GH55 Capsule in combination with GH21 Capsule

EXPERIMENTAL

Drug: Phase I dose escalation; Drug: Phase I: Dose Expansion; Drug: phase II

Interventions

Phase I dose escalation DRUG

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.

GH55 Capsule in combination with GH21 Capsule

Phase I: Dose Expansion DRUG

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.

GH55 Capsule in combination with GH21 Capsule

phase II DRUG

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.

GH55 Capsule in combination with GH21 Capsule

Eligibility Criteria

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

You may qualify if:

• \. Aged 18-80 years (inclusive), regardless of gender.
• \. Histologically or cytologically confirmed locally advanced or metastatic solid tumor with aberrantly activated MAPK signaling pathway (RAS/RAF/MEK/ERK).
• \. Failed standard treatment, has no standard treatment options, refuses standard treatment, or is not eligible for standard treatment at the current stage.
• \. Has at least one measurable tumor lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• \. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• \. Estimated survival time ≥ 3 months.
• \. 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); \<br/\>For patients with --Gilbert syndrome: ≤3×ULN
• Alanine Aminotransferase (ALT) ≤2.5×ULN; \<br/\>For patients with liver metastasis or liver cancer: ≤5×ULN

You may not qualify if:

• \. 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.
• \. Received other unmarketed clinical research drugs or treatments within 4 weeks before the first dose.
• \. Underwent major organ surgery (excluding needle biopsy) or suffered significant trauma within 4 weeks before the first dose.
• \. Used strong inhibitors or inducers of CYP3A4 or P-gp within 1 week before the first dose.
• \. Previously received other selective ERK inhibitors and/or SHP2 inhibitors.
• \. Previously received hematopoietic stem cell transplantation or organ transplantation.
• \. 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).
• \. Symptomatic parenchymal brain metastasis or meningeal metastasis, deemed unsuitable for enrollment by investigators.
• \. Has an active infection requiring intravenous anti-infective treatment.
• \. Has a history of immunodeficiency, including positive HIV antibody test.
• \. 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).
• \. Has a history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

Sponsors & Collaborators

• Suzhou Genhouse Bio Co., Ltd.: lead
• Shanghai Goboard Cancer Hospital: collaborator

Study Sites (1)

Shanghai Goboard Cancer Hospital

Shanghai, Shanghai Municipality, 200000, China

Location

MeSH Terms

Interventions

Clinical Trials, Phase II as Topic

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• JIN LI, DOCTORATE

  Shanghai Goboard Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

QIAN DONG, MASTER

CONTACT

+8615221908116; dongqian@genhousebio.com

SHIYA CHEN, BACHELOR

CONTACT

+8615618310761; chenshiya@genhousebio.com

Study Design

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

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: March 3, 2026
• Study Start: February 24, 2026
• Primary Completion (Estimated): October 30, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)