IN10018 in Combination With RNK08954 for the Treatment of KRASG12D Mutation-Positive Locally Advanced or Metastatic Solid Tumors

February 25, 2026 updated by: InxMed (Shanghai) Co., Ltd.

A Multicenter, Open-Label, Phase Ib/II Clinical Trial of IN10018 in Combination With RNK08954 for the Treatment of KRASG12D Mutation-Positive Locally Advanced or Metastatic Solid Tumors

This is a multicenter, open-label, Phase Ib/II clinical study. The study includes Phase Ib-Dose Exploration Stage and Phase II - Efficacy Exploration and Determination Stage.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, open-label, Phase Ib/II clinical study. The study includes Phase Ib-Dose Exploration Stage and Phase II - Efficacy Exploration and Determination Stage. Phase Ib - Dose Exploration Stage: It is designed to evaluate the safety and preliminary efficacy of IN10018 in combination with RNK08954 for the treatment of KRASG12D mutation-positive locally advanced or metastatic solid tumors, and to determine the Recommended Phase 2 Dose (RP2D) of the combination therapy. Phase II - Efficacy Exploration and Determination Stage: It will further evaluate the anti-tumor efficacy, safety, and pharmacokinetic (PK) characteristics of IN10018 in combination with RNK08954 in KRASG12D mutation-positive locally advanced or metastatic solid tumor (Pancreatic ductal adenocarcinoma (PDAC) shall be prioritized for enrollment). Based on the preliminary efficacy and safety data, one or two advanced solid tumor indications, including but not limited to PDAC, NSCLC, and CRC will be selected for adoption of a factorial or other appropriate study design and determination of sample size. Discussions with Center for Drug Evaluation (CDE) shall be completed prior to initiating the registrational study.

Study Type

Interventional

Enrollment (Estimated)

92

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China
        • Not yet recruiting
        • Cancer Hospital Chinese Academy of Medical Sciences
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China
        • Not yet recruiting
        • Fujian Cancer Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Not yet recruiting
        • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
        • Contact:
    • He
      • Luoyang, He, China
        • Not yet recruiting
        • The First Affiliated Hospital of Henan University of Science And Technology
        • Contact:
    • Henan
      • Zhengzhou, Henan, China
        • Not yet recruiting
        • The First Affiliated Hospital of Zhengzhou University
        • Contact:
    • Hunan
      • Changsha, Hunan, China
        • Not yet recruiting
        • Hunan Cancer Hospital
        • Contact:
    • Jiangsu
      • Nanjing, Jiangsu, China
        • Not yet recruiting
        • Jiangsu Province Hospital
        • Contact:
      • Nanjing, Jiangsu, China
        • Not yet recruiting
        • Affiliated Drum Tower Hospital, Medical School of Nanjing University
        • Contact:
    • Liaoning
      • Shengyang, Liaoning, China
        • Not yet recruiting
        • The First Affiliated Hospital of China Medical University
        • Contact:
    • Shandong
      • Jinan, Shandong, China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China
        • Not yet recruiting
        • Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
        • Contact:
    • Shanxi
      • Xi’an, Shanxi, China
        • Not yet recruiting
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Recruiting
        • Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310005
        • Contact:
      • Wenzhou, Zhejiang, China
        • Not yet recruiting
        • The First Affiliated Hospital of Wenzhou Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1. Voluntarily participate in the study after being fully informed, sign the written ICF, and agree to comply with the procedures specified in the protocol.
  • 2. Male or female aged ≥18 years at the time of signing the ICF.
  • 3. Subjects with pathologically confirmed locally advanced or metastatic solid tumors.
  • 4. Subjects confirmed to be KRASG12D mutation-positive in tumor tissue samples. Subjects may use historical results from local laboratories (within 2 years before signing the ICF).

Note: Test results must be provided by a laboratory certified by the Clinical Laboratory Improvement Amendments (CLIA) or an equivalent certification, a third-party laboratory recognized by the investigator, or the pathology department of grade A tertiary hospital.

  • 5. Requirements for tumor type are as follows:

    1. Phase Ib: Subjects with locally advanced or metastatic solid tumors who have documented radiologically disease progression, and are intolerant to standard treatment, or have no standard treatment, or have failed to standard treatment.
    2. Phase II Cohort 1: Subjects with locally advanced or metastatic PDAC who have previously received gemcitabine- or nab-paclitaxel-based chemotherapy regimens or FOLFIRINOX/mFOLFIRINOX standard treatment and failed to standard treatment (have received at least first-line standard therapy and failed to standard treatment);
    3. Phase II Cohort 2: Subjects with locally advanced or metastatic solid tumors who have documented radiologically disease progression and are intolerant to standard treatment, or have no standard treatment, or have failed to standard treatment (Selected tumor types will be determined based on prior study results).
  • 6. Presence of at least 1 measurable lesion assessable by computed - tomography (CT) or magnetic resonance imaging (MRI) according to RECIST Version 1.1. For lesions previously treated with radiotherapy or other local treatments, radiological confirmation of disease progression is required before they can be considered measurable lesions.
  • 7. ECOG performance status score of 0 or 1.
  • 8. Life expectancy of at least 3 months (assessed by the investigator).

  • 9. Laboratory tests within 7 days before the first dose confirm adequate bone marrow, liver, kidney, and coagulation function reserves, and no blood transfusion or blood products have been received within 14 days before the relevant tests:

    1. Platelets ≥100×10⁹/L, and no platelet transfusion or thrombopoietin (TPO) treatment has been received within 14 days before the screening blood routine test.
    2. Hemoglobin ≥90 g/L, and no blood transfusion, red blood cell transfusion, or erythropoietin (EPO) treatment has been received within 14 days before the screening blood routine test.
    3. Neutrophil count ≥1.5×10⁹/L, and no colony-stimulating factor (CSF) has been used within 14 days before the screening blood routine test.
    4. Creatinine clearance (Clcr) estimated by the Cockcroft-Gault (C-G) formula ≥60 mL/min, or estimated glomerular filtration rate (eGFR) estimated by the Modification of Diet in Renal Disease (MDRD) equation ≥60 mL/min.
    5. Urine protein negative or weakly positive (±); or urine protein 1+, but urine protein-to-creatinine ratio (UPCR) in random morning urine <0.5 or 24-hour urine protein quantification <0.5 g/24 h.
    6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×Upper Limit of Normal (ULN) (≤5×ULN if liver metastasis exists). g) Total bilirubin ≤1.5×ULN (≤3×ULN is allowed for subjects with Gilbert's syndrome).
    7. Prothrombin time and activated partial thromboplastin time ≤1.5×ULN, International Normalized Ratio (INR) ≤1.5. For subjects receiving anticoagulant therapy, INR <3.0 or within the target range of anticoagulant therapy (if applicable).
  • 10. Female subjects of childbearing potential must agree to abstain from sexual intercourse or use effective contraceptive methods from the time of signing the ICF until 6 months after the last dose of study drug. Acceptable contraceptive methods include: oral, injectable, or implantable hormonal contraception; intrauterine device or intrauterine system; male condom with spermicide or occlusive cap (diaphragm or cervical/vaginal cap).
  • 11. Male subjects must agree to abstain from sexual intercourse, undergo sterilization surgery, or use effective contraceptive methods from the time of signing the ICF until 6 months after the last dose of study drug.

Note: Effective contraceptive methods include: use of a male condom, with the female partner also using hormonal contraception or an intrauterine device (used for at least 4 weeks before administration); use of a male condom, with the female partner also using a diaphragm with spermicide or a cervical/vaginal cap.

Exclusion Criteria:

  • 1. Previous treatment with KRASG12D inhibitors. Note: Except for subjects in Phase Ib, who may have received previous treatment with KRASG12D inhibitors.
  • 2. Previous treatment with focal adhesion kinase (FAK) inhibitors.
  • 3. Received any anti-cancer drug treatment (including cytotoxic therapy, targeted therapy, biological therapy, or hormonal therapy other than alternative therapy) or other investigational drug treatment and radiotherapy within 14 days before the first dose.
  • 4. Have other KRAS mutations (excluding KRASG12D mutation), and have other positive mutation sites with available marketed targeted drugs.
  • 5. Subjects with known spinal cord compression symptoms, unstable or symptomatic/progressive central nervous system (CNS) metastasis, or meningeal metastasis. Subjects with a history of brain metastasis who are clinically and radiologically stable (i.e., no progression of CNS disease confirmed by two consecutive brain MRI or CT scans (if MRI is not suitable) with an interval of at least 4 weeks) may be enrolled (if the subject has previously received radiotherapy for brain metastasis, the MRI or CT scan must be performed at least 4 weeks after the last brain radiotherapy). For subjects who have received corticosteroid treatment, corticosteroids must have been discontinued for at least 2 weeks before the first dose of study drug. For subjects receiving anti-epileptic treatment, their medication dose must have been stable for at least 2 weeks.

  • 6. Any of the following cardiovascular conditions:

    1. Congestive heart failure with New York Heart Association (NYHA) functional class II or higher.
    2. Severe arrhythmia and left bundle branch block requiring drug treatment.
    3. Acute myocardial infarction, severe or unstable angina pectoris, coronary or peripheral artery bypass surgery within 6 months before the first dose.
    4. Left ventricular ejection fraction (LVEF) <50%.
    5. Prolonged corrected QT interval (QTcF) by Fridericia's formula at rest, with an average QTc interval >480 ms measured by three consecutive ECGs, or risk factors for torsades de pointes, such as clinically significant hypokalemia, family history of long QT syndrome, or familial arrhythmia (e.g., Pre-excitation Syndrome) as judged by the investigator.
    6. Uncontrolled hypertension (defined as systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg after standardized antihypertensive drug treatment).
    7. Deep vein thrombosis (other than implantable venous access port or catheter-related thrombosis) or pulmonary embolism within 6 months prior to the first dose of study treatment.
  • 7. Subjects with stroke or other severe cerebrovascular diseases (e.g., acute cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage) within 12 months prior to the first dose of study treatment.
  • 8. Subjects with interstitial lung disease or any active infection requiring systemic treatment within 14 days prior to the first dose of study treatment, including but not limited to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
  • 9. Subjects with active autoimmune diseases (e.g., autoimmune thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease) requiring systemic treatment (including disease-modifying drugs, corticosteroids, or immunosuppressants) within the past 2 years. Hashimoto's thyroiditis, vitiligo, and psoriasis that do not require systemic treatment are excluded. Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
  • 10.The investigator judges that the subject has a history or evidence of substance abuse, or has medical, psychological, or social conditions that may interfere with study participation or evaluation of study results.

Note: The following conditions are not recommended for enrollment, including but not limited to: 1) Presence of pleural effusion, pericardial effusion, or ascites that is poorly controlled and requires clinical management; 2) Active bleeding such as hemoptysis or gastrointestinal bleeding during the screening period, subjects with only a small amount of blood in sputum are allowed to enroll; 3) Received live vaccines or attenuated live vaccines within 28 days prior to the first dose of study treatment.

  • 11.Subjects with gastrointestinal (GI) disorders that may significantly impair the oral administration, absorption, or metabolism of the study drug, including dysphagia, refractory nausea and vomiting, malabsorption syndrome, gastrectomy or small bowel resection that impairs the oral absorption or metabolism of the study drug, symptomatic inflammatory bowel disease, and partial or complete intestinal obstruction.

Note: Subjects with clinical or radiological evidence of intestinal obstruction, or those who developed intestinal obstruction within the previous 3 months with unresolved underlying cause are not recommended for enrollment.

  • 12.The subject has not recovered from the toxicity of previous anti-tumor treatment (except for alopecia and pigmentation), defined as not recovered to NCI CTCAE v5.0 ≤Grade 1 (≤Grade 2 for peripheral neuropathy).
  • 13.The subject has undergone major surgery within 4 weeks prior to the first dose of study drug or has not fully recovered from previous surgical treatment. For percutaneous liver biopsy and other needle biopsies, a 14-day washout period is required before the first dose of study treatment.

Note: Subjects expected to undergo major surgery or those who need to interrupt study medication for scheduled surgery during the study treatment, should also be excluded.

  • 14.The subject has received or plans to receive within 2 weeks before the first dose of study drug treatment:

    1. Drugs that are known to be narrow therapeutic window substrates of CYP3A.
    2. Drugs that are known to be strong inducers or inhibitors of CYP3A4.
    3. Drugs that are known to be strong inhibitors of P-glycoprotein.
    4. Drugs known/potentially causing QTc interval prolongation or torsades de pointes (e.g., antiarrhythmic drugs).

Note: For details, refer to Appendix 9 in Section 10.9.

  • 15.Pregnant or lactating women.
  • 16.Positive for hepatitis B surface antigen (HBsAg) with hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥2500 copies/mL or 500 IU/mL, positive for hepatitis C virus (HCV) antibody with HCV ribonucleic acid (HCV RNA) above the lower limit of detection, or positive for human immunodeficiency virus (HIV) antibody.
  • 17.A history of other malignant tumors within 5 years before the first dose, except for cured basal cell carcinoma of the skin, carcinoma in situ (e.g., carcinoma in situ of the breast, squamous cell carcinoma in situ of the skin, cervical carcinoma in situ).
  • 18.Known allergy (such as life-threatening hypersensitivity reaction) or other intolerances to IN10018, RNK08954 or their pharmaceutical excipients; or subjects with severe allergic diathesis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: IN10018 in combination with RNK08954
IN10018 100mg QD PO + RNK08954 1000mg/1200mg QD PO Subject should take study drug till PD.
Drug: IN10018 in combination with RNK08954
Based on existing clinical data, the RP2D of IN10018 as monotherapy and in combination with chemotherapy, targeted therapy, and immunotherapy is 100 mg QD. For RNK08954 as monotherapy, the Maximum Tolerated Dose (MTD) was not reached during the dose escalation of the Phase I study, and effective doses with observed tumor responses were 800 mg QD, 1000 mg QD, and 1200 mg QD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase Ib:Recommended phase II dose (RP2D) of IN10018 in combination with RNK08954
Time Frame: Approximately 6 months
Determine the Recommended Phase 2 Dose (RP2D) of IN10018 in combination with RNK08954 in subjects with KRAS G12D mutation-positive locally advanced or metastatic solid tumors by evaluating up to 18 subjects with dose-limited toxicities (DLTs).
Approximately 6 months
Phase II: To evaluate the rate of Objective Response Rate (ORR) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
Time Frame: Approximately 5 years
Defined as the proportion of subjects with complete response (CR) or partial response (PR).
Approximately 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the rate of Objective Response Rate (ORR) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
Time Frame: Approximately 5 years
ORR：Defined as the proportion of subjects with complete response (CR) or partial response (PR).
Approximately 5 years
To evaluate the time of Duration of Response (DoR) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
Time Frame: Approximately 5 years
DoR：Defined as the time from start of the first documentation of CR or PR to the first documentation of disease progression or to death due to any cause, whichever comes first.
Approximately 5 years
To evaluate the rate of Disease Control Rate (DCR) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
Time Frame: Approximately 5 years
DCR：Defined as the proportion of patients with CR, PR, or stable disease (SD).
Approximately 5 years
To evaluate the duration of Progression-free Survival (PFS) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
Time Frame: Approximately 5 years
Defined as the time from the first dose of study treatment to first documentation of disease progression or to death due to any cause, whichever comes first.
Approximately 5 years
To Evaluate the duration of Overall survival (OS) of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
Time Frame: Approximately 5 years
Defined as the time from the first dose of study treatment to the date of death due to any cause.
Approximately 5 years
To collect number of subjects with adverse event during the study.
Time Frame: Approximately 5 years
The adverse event include but not limited to abnormal lab report which investigator consider clinical significant, any suffering, pain, accident event during the study.
Approximately 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
PK: AUC0-τ of IN10018 and RNK08954
Time Frame: Approximately 5 years
Area Under the Plasma Concentration-Time Curve from Time 0 to the Dosing Interval (AUC0-τ) of IN10018 and RNK08954.
Approximately 5 years
PK: AUC0-∞ of IN10018 and RNK08954
Time Frame: Approximately 5 years
Area Under the Plasma Concentration-Time Curve from Time 0 to Infinity (AUC0-∞)
Approximately 5 years
PK: Cmax of IN10018 and RNK08954
Time Frame: Approximately 5 years
Maximum Plasma Concentration (Cmax)
Approximately 5 years
PK: Ctrough of IN10018 and RNK08954
Time Frame: Approximately 5 years
Trough Plasma Concentration (Ctrough)
Approximately 5 years
PK: Tmax of IN10018 and RNK08954
Time Frame: Approximately 5 years
Time to Reach Maximum Plasma Concentration (Tmax)
Approximately 5 years
PK: t1/2 of IN10018 and RNK08954
Time Frame: Approximately 5 years
Elimination Half-Life (t1/2)
Approximately 5 years
Plasma concentrations of IN10018 in combination with RNK08954
Time Frame: Approximately 5 years
Plasma concentrations of IN10018 in combination with RNK08954 in subjects with KRASG12D mutation-positive locally advanced or metastatic solid tumors.
Approximately 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

InxMed (Shanghai) Co., Ltd.

Collaborators

Ranok Therapuetics Co. Ltd.
InxMed (Shenzhen) Co.,Ltd.

Investigators

  • Principal Investigator: Zhengbo Song, M.D, Zhejiang Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 28, 2026

Primary Completion (Estimated)

February 28, 2031

Study Completion (Estimated)

February 28, 2031

Study Registration Dates

First Submitted

February 13, 2026

First Submitted That Met QC Criteria

February 25, 2026

First Posted (Actual)

February 27, 2026

Study Record Updates

Last Update Posted (Actual)

February 27, 2026

Last Update Submitted That Met QC Criteria

February 25, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • IN10018-026/RNK08954-02

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

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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