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

NCT07441174 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IN10018-026/RNK08954-02
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Solid Tumor Cancer; PDAC

Keywords

KRASG12D mutation-positive

Outcome Measures

Primary Outcomes (2)

• Phase Ib:Recommended phase II dose (RP2D) of IN10018 in combination with RNK08954

  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.

  Defined as the proportion of subjects with complete response (CR) or partial response (PR).

  Approximately 5 years

Secondary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  Approximately 5 years

Other Outcomes (7)

• PK: AUC0-τ of IN10018 and RNK08954

  Approximately 5 years

• PK: AUC0-∞ of IN10018 and RNK08954

  Approximately 5 years

• PK: Cmax of IN10018 and RNK08954

  Approximately 5 years

Study Arms (1)

IN10018 in combination with RNK08954

OTHER

IN10018 100mg QD PO + RNK08954 1000mg/1200mg QD PO Subject should take study drug till PD.

Drug: IN10018 in combination with RNK08954

Interventions

IN10018 in combination with RNK08954 DRUG

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.

IN10018 in combination with RNK08954

Eligibility Criteria

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

You may qualify if:

• \. Voluntarily participate in the study after being fully informed, sign the written ICF, and agree to comply with the procedures specified in the protocol.
• \. Male or female aged ≥18 years at the time of signing the ICF.
• \. Subjects with pathologically confirmed locally advanced or metastatic solid tumors.
• \. 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.
• \. Requirements for tumor type are as follows:
• 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.
• 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);
• 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).
• \. 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.
• \. ECOG performance status score of 0 or 1.
• \. Life expectancy of at least 3 months (assessed by the investigator).
• \. 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:
• Platelets ≥100×10⁹/L, and no platelet transfusion or thrombopoietin (TPO) treatment has been received within 14 days before the screening blood routine test.
• 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.

You may not qualify if:

• \. Previous treatment with KRASG12D inhibitors. Note: Except for subjects in Phase Ib, who may have received previous treatment with KRASG12D inhibitors.
• \. Previous treatment with focal adhesion kinase (FAK) inhibitors.
• \. 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.
• \. Have other KRAS mutations (excluding KRASG12D mutation), and have other positive mutation sites with available marketed targeted drugs.
• \. 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.
• \. Any of the following cardiovascular conditions:
• Congestive heart failure with New York Heart Association (NYHA) functional class II or higher.
• Severe arrhythmia and left bundle branch block requiring drug treatment.
• Acute myocardial infarction, severe or unstable angina pectoris, coronary or peripheral artery bypass surgery within 6 months before the first dose.
• Left ventricular ejection fraction (LVEF) \<50%.
• 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.
• Uncontrolled hypertension (defined as systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg after standardized antihypertensive drug treatment).
• 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.
• \. 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.
• \. 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.

Sponsors & Collaborators

• InxMed (Shanghai) Co., Ltd.: lead
• Ranok Therapuetics Co. Ltd.: collaborator
• InxMed (Shenzhen) Co.,Ltd.: collaborator

Study Sites (14)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

NOT YET RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, China

NOT YET RECRUITING

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

NOT YET RECRUITING

The First Affiliated Hospital of Henan University of Science and Technology

Luoyang, He, China

NOT YET RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

NOT YET RECRUITING

Affiliated Drum Tower Hospital, Medical School of Nanjing University

Nanjing, Jiangsu, China

NOT YET RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, China

NOT YET RECRUITING

The First Affiliated Hospital of China Medical University

Shengyang, Liaoning, China

NOT YET RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, China

NOT YET RECRUITING

Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, China

NOT YET RECRUITING

Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310005

Hangzhou, Zhejiang, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

NOT YET RECRUITING

Study Officials

• Zhengbo Song, M.D

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shangyu Chen, Bachelor

CONTACT

86+18752093074; shangyu.chen@inxmed.com

Lily LI, Bachelor

CONTACT

13911551669; lily.li@inxmed.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: February 13, 2026
• First Posted: February 27, 2026
• Study Start: February 28, 2026
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): February 28, 2031
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (14)