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).
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).
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.
Presence of active or symptomatic untreated central nervous system (CNS) metastases.
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.
Single group
RNK08954-01
DrugOnce daily oral treatment for a 3 week cycle
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
Optimal Biological Dose (OBD).
To determine the Recommended Dose for Expansion (RDE) of RNK08954 monotherapy in adult patients with KRAS G12D mutant solid tumors.
Dose limiting toxicities (DLT)
To Determine Maximum Tolerated Dose (MTD) of RNK08954 monotherapy in adult patients with KRAS G12D mutant solid tumors
Objective response rate (ORR)
To determine the clinical activity of RNK08954 as monotherapy
Overall survival (OS), 1-year survival rate.
To determine the clinical activity of RNK08954 as monotherapy
.Evaluate Area under the plasma concentration (AUC0-72) in the fasted and fed states.
To evaluate the effect of food on the exposure of RNK08954
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