GST101 in Participants With RAS-Mutant Advanced Solid Tumors

NCT07868172 | Not Yet Recruiting Phase 1

• 1 other identifier: GST101-001
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, multicenter Phase I/II trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of oral GST101 in adult participants with RAS-mutant advanced solid tumors. Phase I consists of dose escalation and dose-expansion parts. Dose escalation uses accelerated titration design combined with 3+3 design to determine maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). Safety, dose-limiting-toxicity (DLT), PK and preliminary efficacy will be assessed. Phase II (indication-exploration) enrolls participants in four tumor-specific cohorts including RAS-mutant NSCLC, colorectal cancer, pancreatic ductal adenocarcinoma and other advanced solid tumors refractory to standard-of-care therapies. Participants receive GST101 orally once-daily in 21-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or loss of clinical benefit. Tumor assessments follow RECIST 1.1. Safety, PK, QTc and exploratory biomarker analyses will be performed.

Conditions

RAS-mutant Advanced Solid Tumors

Outcome Measures

Primary Outcomes (5)

• Number of Participants with Dose-Limiting Toxicity (DLT)

  The number of participants experiencing dose-limiting toxicities (DLT) during the dose-escalation period of the study.

  At the end of Cycle 1 (each cycle is 21 days)

• Incidence and Severity of Treatment-Emergent Adverse Events (AEs) and Serious AEs

  The incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including abnormalities in laboratory values and vital signs.

  Up to 36 months

• Maximum Tolerated Dose (MTD)

  To determine the maximum tolerated dose of GST101

  Up to 12 months

• Recommended Phase 2 Dose (RP2D)

  To determine the recommended phase 2 dose of GST101

  Up to 12 months

• Objective Response Rate (ORR)

  Objective response rate (ORR) as assessed by the investigator per RECIST v1.1

  Up to 36 months

Secondary Outcomes (8)

• Duration of Response (DOR)

  Up to 36 months

• Disease Control Rate (DCR)

  Up to 36 months

• Progression-Free Survival (PFS)

  Up to 36 months

• Overall Survival (OS)

  Up to 36 months

• Maximum Observed Blood Concentration (Cmax) of GST101

  Up to 36 weeks

Study Arms (1)

GST101 Monotherapy

EXPERIMENTAL

Participants receive oral GST101 once-daily in 21-day treatment cycles. Multiple dose levels (10 mg, 20 mg, 40 mg, 60 mg, 80 mg, 100 mg) are evaluated in sequential dose-escalation cohorts using accelerated titration design (ATD) combined with a 3+3 design. Selected safe doses will enter dose-expansion. Phase II indication-exploration cohorts will adopt the recommended Phase II dose (RP2D) determined from Phase I. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or loss of clinical benefit. Participants are required to fast for 1-hour before dosing and 2-hours after dosing.

Drug: GST101

Interventions

GST101 DRUG

5 mg oral tablet, administered once daily. Participants are assigned to different dose-level cohorts (10 mg, 20 mg, 40 mg, 60 mg, 80 mg, 100 mg). Fasting requirement: 1-hour fast prior to dosing and 2-hour fast after dosing. Each treatment cycle is 21-days. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or no further clinical benefit.

GST101 Monotherapy

Eligibility Criteria

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

You may qualify if:

• Aged ≥18 years, male or female, with signed informed consent.
• Histologically or cytologically confirmed RAS-mutated advanced solid tumor, with disease progression or intolerance to standard anti-tumor therapy, or no available standard treatment.
• For Phase II cohorts: eligible RAS-mutated advanced NSCLC, colorectal cancer, pancreatic cancer or other solid tumors meeting corresponding line-of-treatment criteria.
• ECOG performance status 0 or 1.
• Estimated life expectancy ≥ 3 months.
• At least one measurable lesion per RECIST 1.1.
• Adequate hematological, hepatic and renal organ function without supportive treatment within 14 days before dosing, meeting prespecified laboratory thresholds.
• Fertile participants agree to effective contraception from consent to 4 months after last dose; female participants have negative pregnancy test and no lactation at baseline.

You may not qualify if:

• Symptomatic or uncontrolled central nervous system metastases, spinal cord compression or meningeal carcinomatosis.
• Active or previous malignant tumor within 5 years (except permitted low-risk in-situ or superficial tumors).
• Uncontrolled large-volume serous cavity effusion.
• Active HIV, hepatitis B/C, syphilis or tuberculosis infection.
• History of allogeneic organ or stem cell transplantation.
• Severe uncontrolled cardiovascular, pulmonary, hepatic, renal, neurological or metabolic diseases within 6 months prior to enrollment.
• QTcF \>480 ms, long QT syndrome, reduced left ventricular ejection fraction or uncontrolled severe arrhythmia/hypertension.
• Severe cutaneous adverse drug reaction history or uncontrolled electrolyte/metabolic disorders.
• High bleeding risk, active gastrointestinal bleeding or recent venous thromboembolism within 6 months.
• Hypersensitivity to study drug or excipients.
• Pregnancy, lactation, uncontrolled psychiatric disorder or substance abuse.
• Prior treatment with any RAS-targeted inhibitor.
• Receipt of prohibited anti-tumor drugs, strong CYP3A modulators within required washout periods before dosing.
• Unresolved \>Grade 1 toxicity from prior anti-tumor therapy.
• Impaired oral drug absorption or inability to take oral medication.

Sponsors & Collaborators

• Genuine Seed Therapeutics (Zhuhai) Co., Ltd.: lead

Study Sites (2)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

Location

Study Officials

• Caicun Zhou, MD, PhD

  Shanghai East Hospital

  STUDY CHAIR

• Xianjun Yu, MD, PhD

  Fudan University

  STUDY CHAIR

Central Study Contacts

Xiaoli Shi, MMed

CONTACT

+86 18701056862; xiaoli.shi@gseedtx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2026
• First Posted: October 9, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: October 9, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)