A Study of RNK08954 in Subjects With Advanced Solid Tumors With KRAS ((Kirsten Rat Sarcoma) G12D Mutation

NCT06667544 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: RNK08954-01
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 6

Brief Summary

This is a first in human (FIH), Phase 1/2 open-label multi-center, dose escalation and expansion study to evaluate the safety, tolerability and pharmacokinetics of RNK08954 to determine the optimal dose and recommended dose for expansion and evaluate clinical activity in patients with advanced solid tumors with KRAS G12D mutation. This is a 2-part study: dose exploration/indication expansion and dose optimization ( to identify a dose that preserves clinical benefit with optimal tolerability).

Conditions

KRAS G12D Mutation

Outcome Measures

Primary Outcomes (2)

• Treatment-emergent adverse events (TEAEs).

  To evaluate the safety and tolerability of RNK08954 in adult patients with KRAS G12D mutant solid tumors in approximately 42 subjects

  12-15 months

• Optimal Biological Dose (OBD).

  To determine the Recommended Dose for Expansion (RDE) of RNK08954 monotherapy in adult patients with KRAS G12D mutant solid tumors.

  12-15 months

Secondary Outcomes (4)

• Dose limiting toxicities (DLT)

  12-15 months

• Objective response rate (ORR)

  12-15 months

• Overall survival (OS), 1-year survival rate.

  12-15 months

• .Evaluate Area under the plasma concentration (AUC0-72) in the fasted and fed states.

  12-15 months

Study Arms (1)

RNK08954

EXPERIMENTAL

Dose-escalation of RNK08954 oral dose therapy once daily.

Drug: RNK08954-01

Interventions

RNK08954-01 DRUG

Once daily oral treatment for a 3 week cycle

RNK08954

Eligibility Criteria

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

You may qualify if:

• Must be 18 years of age or older.
• Must have pathologically documented locally advanced or metastatic malignancy harboring KRAS G12D mutations identified through deoxyribonucleic acid (DNA) sequencing of tumor tissues or circulating deoxyribonucleic acid (ctDNA) performed locally.
• Must have received prior standard therapy appropriate for their tumor type, or in the opinion of the investigator, would be unlikely to derive further clinically meaningful benefit from appropriate standard of care therapy.
• Must have measurable lesion(s) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 by Computed tomography (CT) scan with contrast (magnetic resonance imaging (MRI), if the patient is allergic to contrast media).
• Measurable disease may be in the field of prior irradiation; however, at least 3 weeks must have elapsed between the completion of radiation therapy and the baseline scan documenting disease status.
• Bone disease is considered radiologically measurable only if there is at least a 50% lytic component.
• NOTE: Bone disease consisting of only blastic lesion is not considered measurable.
• NOTE: in Phase 1a, patients must have measurable or evaluable disease.
• Archival or fresh tumor tissue must be available for evaluating relevant biomarkers. Formalin-fixed paraffin-embedded (FFPE)block preferred, or a minimum of 3 unstained FFPE slides of one archived block is required.
• NOTE: cytology samples from fine needle aspirates or brushing biopsies are not sufficient.
• NOTE: Phase 1a and 1b: Patients are additionally encouraged to undergo pre-treatment tumor biopsy.
• Must have adequate performance status, Appendix D.
• o Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0, or 1.
• Must be able to take oral medications and willing to record daily adherence to the investigational product.
• Must have adequate laboratory parameters at baseline:

You may not qualify if:

• A patient is not eligible to participate in the study if any of the following criteria are met:
• Concurrent anticancer therapy \[chemotherapy, monoclonal antibodies, targeted therapy, hormonal therapy or investigational agents\] within the lesser of 28 days or 5 half-lives before study Day 1.
• NOTE: Patient must agree not to participate in any other interventional clinical studies during their participation in this trial while on study treatment.
• NOTE: patients receiving hormonal ablation therapy for breast cancer or hormone refractory prostate cancer are allowed.
• NOTE: Patients taking part in surveys or observational studies are eligible to participate in this study.
• Significant acute decline in clinical status including:
• Decline in ECOG PS to \>1 between baseline visit and within 72 hours prior to starting study treatment.
• Weight loss of ≥10% during screening.
• Presence of active or symptomatic untreated central nervous system (CNS) metastases.
• NOTE: Patients with asymptomatic or stable CNS metastases are eligible, provided that the CNS metastases are radiologically and clinically stable for at least 2 weeks prior to enrollment, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
• Unresolved toxicities from prior anticancer therapy, defined as not having resolved according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade ≤ 1, or to levels dictated in the eligibility criteria, with the exception of alopecia.
• Prior radiotherapy to the only area of measurable disease, unless there is documented disease progression.
• NOTE: Patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of the first dose of RNK08954.
• Presence of gastrointestinal (GI) tract disease causing inability to take oral medication, such as malabsorption syndrome, requirement for intravenous alimentation, uncontrolled inflammatory GI disease, e.g. Crohn's disease or ulcerative colitis, or any other severe acute or chronic condition that may increase the risk of study participation including, e.g. history of abdominal fistula, GI perforation, peptic ulcer.
• Current or history within 6 months prior to study enrollment of medically significant cardiovascular disease including symptomatic congestive heart failure \> New York Heart Association (NYHA) Class II, unstable angina pectoris, clinically significant cardiac arrhythmia, or a history of long QT Syndrome (the heart's electrical activity as graphed on an electrocardiogram) or a family member with this condition.

Sponsors & Collaborators

• Ranok Therapeutics (Hangzhou) Co., Ltd.: lead

Study Sites (6)

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

RECRUITING

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, China

RECRUITING

Shanghai Chest Hospital

Shanghai, China

RECRUITING

Study Officials

• Zhengbo Song, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xin Wu

CONTACT

86571-86630936; xinwu@ranoktherapeutics.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

Model Details: PK-guided single-patient cohort followed by, A U-BOIN (Utility-based Bayesian Optimal Interval) design, with an incorporated Accelerated Titration (AT) step in the first dose level and then will enroll a minimum of 3 patients per dose level.

Study Record Dates

• First Submitted: October 28, 2024
• First Posted: October 31, 2024
• Study Start: November 8, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: October 30, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)