Phase Ib Study of Oral R01 Monotherapy in Advanced Solid Tumors

NCT07806500 | Not Yet Recruiting Phase 1

• 1 other identifier: GBMT-R01-P02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I（Ib）, open-label, single-arm clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of R01 administered orally as monotherapy twice daily (BID) in patients with advanced solid tumors, including squamous cell lung cancer, gastric cancer , and esophageal cancer. Patients with advanced squamous cell lung cancer, gastric cancer , and esophageal cancer will be enrolled. All subjects will receive oral R01 monotherapy and will undergo physical examinations, laboratory tests, radiographic tumor response assessments, biological sample collection, and safety follow-ups as specified in the protocol. The study comprises two consecutive sub-stages: a dose-bridging escalation stage (i.e., a dose escalation stage designed to bridge from the highest dose evaluated in Phase Ia) and a dose expansion stage. The dose escalation follows a classic '3+3' design at three dose levels (240, 320, and 400 mg BID). The 400 mg dose may be initiated after the Safety Review Committee (SRC) review based on safety and PK data. The primary objectives of this stage are to characterize dose-limiting toxicities (DLTs), determine the maximum tolerated dose (MTD), and establish the recommended Phase II dose (RP2D). The dose expansion stage will be conducted at the RP2D in selected indication cohorts, with a planned enrollment of at least 6 subjects per cohort (including subjects with the corresponding indications enrolled at the same dose level during the dose escalation stage), to further evaluate the safety, tolerability, PK characteristics, and preliminary antitumor efficacy at this dose level. With respect to study endpoints: during the dose escalation stage, the primary endpoints are the incidence of DLTs, the MTD, and/or the determination of the expansion dose (RP2D); secondary endpoints include PK parameters of R01 and its metabolites, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). During the dose expansion stage, the primary endpoints are ORR and the incidence and severity of treatment-related adverse events (TRAEs); secondary endpoints include duration of response (DOR), time to response (TTR), DCR, PFS, OS, and steady-state PK parameters.

Conditions

Squamous Cell Lung Cancer; Gastric Cancer; Esophageal Cancer

Outcome Measures

Primary Outcomes (4)

• Number of Participants with Dose-Limiting Toxicities (DLTs)

  Dose-limiting toxicity (DLT) is defined as a toxicity occurring during the observation window at any dose level, judged by the investigator to be related to R01, and meeting any of the following criteria: Hematologic toxicities: Grade 4 hematologic toxicity; Grade 4 neutropenia persisting for \>7 days despite G-CSF treatment; Grade 4 anemia not recovering to ≤Grade 2 within 14 days despite transfusion support; Grade 4 thrombocytopenia regardless of bleeding; Febrile neutropenia ; Grade 3 thrombocytopenia with clinically significant bleeding. Non-hematologic toxicities: Grade ≥3 non-hematologic toxicity; QTcF \>500 ms or increase of \>60 ms from baseline confirmed by repeat ECG; Grade ≥3 hypoxemia or Grade ≥3 dyspnea; Actual dosing in Cycle 1 \<75% of planned dose or dosing delay \>14 days due to study drug-related toxicity. DLTs will be assessed according to CTCAE v6.0 during the DLT observation window.

  Cycle 1 (21 days)

• Determination of Maximum Tolerated Dose (MTD) and/or Expansion Dose

  The maximum tolerated dose (MTD) is defined as the highest dose level at which ≤1 of 6 participants experiences a dose-limiting toxicity (DLT) during the DLT observation window. DLTs will be assessed according to CTCAE v6.0. The MTD will be determined using a standard 3+3 dose escalation design. The expansion dose will be selected based on the MTD, pharmacokinetic exposure, safety, tolerability, and preliminary efficacy observed during the dose escalation phase, and will not exceed the MTD.

  From the beginning of first patient in (FPl) to the end of dose escalation phase up to approximately 9 months

• Objective Response Rate (ORR)

  Objective response rate (ORR) is defined as the proportion of participants who achieve a confirmed best overall response of complete response (CR) or partial response (PR), as assessed by the investigator according to RECIST version 1.1. CR is defined as the disappearance of all target lesions and any pathological lymph nodes (short axis \<10 mm). PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. All responses must be confirmed by a repeat assessment performed no less than 4 weeks after the initial response is first documented. ORR will be reported for each dose cohort and for the overall study population. The 95% confidence interval (CI) for ORR will be calculated using the Clopper-Pearson exact method.

  From the beginning of first patient in (FPl) to the end of dose expansion phase up to approximately 4 months

• Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs)

  Treatment-emergent adverse events (TEAEs) are defined as adverse events that start or worsen in severity after the first dose of study drug (R01) through 30 days after the last dose of study drug, or until initiation of another antineoplastic therapy, whichever occurs first. Treatment-related adverse events (TRAEs) are defined as TEAEs for which the investigator assesses a causal relationship to the study drug as possibly, probably, or definitely related. The incidence and severity of TEAEs and TRAEs will be summarized by dose cohort and for the overall safety population. Severity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.

  From first dose to 30 days after last dose

Secondary Outcomes (7)

• Pharmacokinetic (PK) parameters of R01 and its metabolites

  Cycle 0 (single-dose PK, 3 days); Cycle 1 (steady-state PK, 21 days)

• Objective response rate (ORR)

  From the beginning of first patient in (FPl) to the end of dose escalation phase up to approximately 9 months

• Disease control rate (DCR)

  From the beginning of first patient in (FPI) to the end of study up to approximately 13 months

• Progression-free survival (PFS)

  From the beginning of first patient in (FPI) to the end of study up to approximately 13 months

• Overall survival (OS)

  From the beginning of first patient in (FPI) to the end of study up to approximately 13 months

Other Outcomes (2)

• Change from Baseline in Functional Pharmacodynamic Parameters (Hemoglobin, Red Blood Cell Count, and Reticulocyte Count)

  From the beginning of first patient in (FPI) to the end of study up to approximately 13 months

• Exploratory Biomarker Analysis and Association with Drug Exposure and Clinical Efficacy

  From the beginning of first patient in (FPI) to the end of study up to approximately 13 months

Study Arms (1)

Experimental: R01 Oral Monotherapy

EXPERIMENTAL

This is a single-arm, open-label study consisting of a dose escalation phase and a dose expansion phase. The investigational product R01 is an oral formulation for the treatment of patients with advanced solid tumors.The dose escalation phase will evaluate three prespecified dose levels (240 mg BID, 320 mg BID, and 400 mg BID). Participants will be enrolled sequentially to determine the maximum tolerated dose (MTD) and/or the recommended dose for expansion. In the dose expansion phase, participants will uniformly receive the expansion dose determined during the dose escalation phase to further evaluate safety and preliminary efficacy.All participants will receive oral R01 twice daily, with each treatment cycle consisting of 21 days. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of informed consent, or other discontinuation criteria specified in the protocol.

Drug: R01

Interventions

R01 DRUG

The study consists of two parts: (1) Dose Escalation Phase: Three prespecified escalating dose levels will be evaluated: 240 mg BID, 320 mg BID, and 400 mg BID. (2) Dose Expansion Phase: Subjects will receive the expansion dose determined in the dose escalation phase. All subjects will receive R01 orally, twice daily, with each treatment cycle consisting of 21 days. Treatment will continue until the discontinuation criteria specified in the study protocol are met.

Experimental: R01 Oral Monotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age: 18 to 75 years (inclusive), of any sex.
• \. Patients with unresectable squamous cell lung cancer, gastric cancer, or esophageal cancer confirmed by histology or cytology, specifically including those in whom existing standard therapy has failed (≥1 line) or who cannot tolerate standard therapy, or who have evidence of locoregional recurrence or metastasis and are not suitable for curative-intent surgical resection or radiotherapy; the investigator comprehensively assesses that the clinical trial participant is not suitable to receive standard treatment.
• \. Tumor type: advanced squamous cell lung cancer, gastric cancer (including signet-ring cell gastric cancer), and esophageal cancer.
• \. At screening, presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Tumor lesions previously treated with radiotherapy or other locoregional therapy are considered measurable only if progressive disease (PD) at the treated site has been clearly documented after completion of the treatment.
• \. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• \. Expected survival of at least 12 weeks.
• \. Essentially normal function of major organs, with laboratory values at screening meeting the following criteria:
• ANC ≥1500/mm³ (1.5×10⁹/L);
• PLT ≥75,000/mm³ (75×10⁹/L);
• Hb ≥9 g/dL (90 g/L) (most recent test during the screening period, and within 7 days before the first dose);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) both ≤2.5× the upper limit of normal (ULN); if liver metastases are present, both ALT and AST ≤5.0× ULN;
• Total bilirubin (TBIL) ≤1.5× ULN;
• Serum creatinine (SCr) ≤1.5× ULN or estimated creatinine clearance (CrCl) ≥50 mL/min (according to the Cockcroft-Gault formula);
• Albumin (ALB) ≥28 g/L;
• Serum potassium ≥3.5 mmol/L and ≤5.5 mmol/L.

You may not qualify if:

• Patients meeting any of the following criteria will not be enrolled in this study:
• \. Patients with advanced disease at risk of life-threatening complications in the short term (patients with visceral crisis).
• \. Known or symptomatic active CNS metastases, manifesting as clinical symptoms, cerebral edema, spinal cord compression, carcinomatous meningitis, leptomeningeal disease, and/or progressive growth.
• \. Major surgery, chemotherapy, radiotherapy, any investigational drug, or other anti-cancer therapy within 4 weeks before the first dose.
• \. Patients who have not been withdrawn from another clinical trial within 4 weeks before study entry, or who are currently participating in another clinical trial involving an investigational drug or device.
• \. Known history of allergy or suspected allergic symptoms to any component of the R01 formulation.
• \. Use, within 14 days or 5 drug half-lives before the first dose (whichever is shorter), of: drugs known to be strong inhibitors/inducers of CYP3A4 or CYP2D6; drugs known to significantly prolong the QT interval.
• \. At screening, a mean corrected QT interval (QTcF) \>480 msec based on the average of 3 ECG assessments at rest (repeat testing and averaging of 3 values is required only if the first ECG indicates QTcF \>480 msec); history of long QT syndrome or a confirmed family history of long QT syndrome; history of clinically significant ventricular arrhythmia, or current use of antiarrhythmic drugs, or an implanted defibrillation device used to treat ventricular arrhythmia.
• \. Uncontrolled electrolyte disturbances that may affect the action of drugs that prolong the QTcF interval (e.g., hypocalcemia below the lower limit of normal (LLN), hypokalemia \<3.5 mmol/L, hyperkalemia \>5.5 mmol/L).
• \. Concurrent severe/unstable angina pectoris; persistent arrhythmia of NCI CTCAE version 6.0 grade ≥2; atrial fibrillation of any grade; symptomatic congestive heart failure; cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism); myocardial infarction within 6 months, or prior coronary/peripheral artery bypass surgery.
• \. Clinically significant active infections, including hepatitis B, hepatitis C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related diseases, syphilis, active tuberculosis infection, and other diseases posing a risk of transmission, as well as uncontrolled systemic bacterial/fungal/other viral infections. Active hepatitis B is defined as: positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg), with hepatitis B virus deoxyribonucleic acid (HBV-DNA) ≥2000 IU/mL (equivalent to 10⁴ copies/mL); active hepatitis C is defined as a positive HCV RNA test result; active syphilis is defined as a positive rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test or the presence of clinical symptoms; active tuberculosis infection is defined as a positive T-SPOT.TB test or positive tuberculin skin test with purified protein derivative (PPD).
• \. Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities, that may increase the risk of participating in the study or the risk associated with administration of the investigational drug, or that may interfere with the study results, as well as any other condition that the investigator considers to make the patient unsuitable for participation in this study.
• \. Diabetic patients whose blood glucose is not effectively controlled (repeated fasting blood glucose \[FBG\] \>7.0 mmol/L).
• \. Persistently elevated corrected serum calcium levels on the 2 most recent independent tests (interval ≥24 h), ≥2.7 mmol/L (10.8 mg/dL) or exceeding the upper limit of the laboratory reference range.
• \. Female clinical trial participants of childbearing potential with a positive pregnancy test at screening, or who do not agree to use highly effective contraception during the study and for 6 months after the last dose; male clinical trial participants who do not agree to use contraception during the study and for 6 months after the last dose, or who do not agree to refrain from donating sperm.

Sponsors & Collaborators

• Beijing Anjianxi Bio-Medical Technology Co., Ltd.: lead

Study Sites (1)

Aerospace Central Hospital, Beijing, China, 100049

Beijing, Beijing Municipality, 100049, China

Location

Related Publications (9)

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MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Study Officials

• Yuankai Shi, MD

  Aerospace Center Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haiyong Wang, PhD

CONTACT

86+18911251079; wanghy@ajxmed.com

Study Design

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

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 8, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 8, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)