RNK08954 for KRAS Mutation

(TRIAD1 Trial)

Recruiting at 7 trial locations

Overseen By Xin Wu

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ranok Therapeutics (Hangzhou) Co., Ltd.

Must not be taking: Herbal medicines, CYP3A4 inhibitors

Disqualifiers: CNS metastases, Cardiovascular disease, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

152 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the safety of a new drug, RNK08954, for individuals with advanced solid tumors that have a specific KRAS G12D mutation, a gene change linked to cancer growth. The study will evaluate how the drug functions and its effects on the body, aiding in the decision of its potential wider use in the future. Individuals diagnosed with tumors carrying this KRAS mutation, who have not found success with standard treatments, might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding the treatment's effects in humans, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot use certain medications that might interact with the study drug, such as strong inhibitors or inducers of specific enzymes. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that RNK08954 is likely to be safe for humans?

Research has shown that RNK08954 is being tested for safety in patients with a specific cancer mutation called KRAS G12D. The studies aim to understand how well patients can tolerate this new treatment. Since RNK08954 is in the early testing stages, limited safety information is available.

Currently, the clinical trials primarily seek to determine the right dose that patients can tolerate without excessive side effects. The goal is to ensure the drug remains effective while maintaining safety. As this is the first time RNK08954 is being tested in humans, researchers are carefully monitoring safety.

Although clear data is not yet available, the trial focuses on safety, with close monitoring of any side effects or adverse reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

RNK08954 is unique because it targets the KRAS mutation, which is a common driver in many cancers and has been notoriously difficult to address with existing treatments. Unlike standard therapies that mostly focus on general cancer cell mechanisms, RNK08954 directly interferes with the mutated KRAS protein's function, potentially stopping cancer cells from growing. Moreover, this treatment is administered orally, which can be more convenient and less invasive compared to traditional infusions or injections. Researchers are excited about RNK08954 because it offers a novel approach to targeting a mutation that has long been considered "undruggable," potentially leading to more effective therapies for patients with KRAS-driven cancers.

What evidence suggests that RNK08954 might be an effective treatment for KRAS mutation?

Research has shown that RNK08954 targets a specific change in cells called the KRAS G12D mutation, often found in some advanced solid tumors. Drugs like RNK08954, known as RAS inhibitors, have demonstrated early signs of effectiveness in different types of cancer. However, some patients may eventually stop responding to the treatment, reducing its long-term effectiveness. The KRAS G12D mutation is usually associated with worse outcomes compared to other types, making treatments like RNK08954 promising options. This trial studies RNK08954 to determine the optimal dose that provides the most benefit with the fewest side effects. ^{1 2 3 4 6}

Who Is on the Research Team?

Zhengbo Song, MD

Principal Investigator

Zhejiang Cancer Hospital

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific genetic change called the KRAS G12D mutation. Participants should not have had previous treatments that didn't work or are no longer working, and they must be in good physical condition to handle the study procedures.

Inclusion Criteria

Must have adequate laboratory parameters at baseline.

Must be able to fast for a minimum of 10 hours.

Must be able to understand and comply with the protocol and have provided written informed consent.

Exclusion Criteria

Known hypersensitivity to any components of the study drug.

I have been diagnosed with hepatitis B or C.

Pregnancy, breast-feeding, or planning to breastfeed during the study or within 6 months after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a: Dose Escalation

Participants receive oral RNK08954 daily in dose escalation cohorts to determine the optimal dose

12-15 months

Phase 1b: Indication Expansion

Multiple indication cohorts open to evaluate the optimal dose in different cancer types

12-15 months

Phase 2: Dose Optimization

Participants receive two different doses of oral RNK08954 daily to compare and further characterize the optimal dose

12-15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RNK08954

Trial Overview The trial is testing RNK08954-01, a new drug for cancer. It's an early-stage study to find out how safe it is, what dose works best, and if it helps against these tumors. Patients will first help find the right dose and then more people will try it at that dose to see how well it works.

How Is the Trial Designed?

Group I: RNK08954 Experimental Treatment 1 Intervention

Dose-escalation of RNK08954 oral dose therapy once daily.

Who Is Running the Clinical Trial?

Ranok Therapeutics (Hangzhou) Co., Ltd.

Lead Sponsor

Trials

2

Recruited

180+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06667544

NCT06667544 | A Study of RNK08954 in Subjects With ... To determine the Recommended Dose for Expansion (RDE) of RNK08954 monotherapy in adult patients with KRAS G12D mutant solid tumors. 12-15 months. Secondary ...

2. synapse.patsnap.com synapse.patsnap.com/drug/7c9a729858204c6c831c4b28096d83c5

RNK08954 - Drug Targets, Indications, Patents - Synapse A Phase 1/2, First-in-Human, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of RNK08954 in Patients With Advanced ...

3. aacrjournals.org aacrjournals.org/cancerdiscovery/article/15/7/1325/763195/Response-and-Resistance-to-RAS-Inhibition-in

Response and Resistance to RAS Inhibition in Cancer RAS inhibitors have shown early evidence of efficacy in multiple cancer types, but clinical benefit is limited by acquired resistance.

4. clin.larvol.com clin.larvol.com/trial-detail/NCT06667544

A Study of RNK08954 in Subjects With Advanced Solid ... To determine the Recommended Dose for Expansion (RDE) of RNK08954 monotherapy in adult patients with KRAS G12D mutant solid tumors. 12-15 months. Secondary ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39777438/

KRAS Mutation Status and Treatment Outcomes in Patients ... In this cohort study of 2433 patients with PDAC, KRAS G12D and G12V mutations were associated with worse patient outcomes compared with KRAS wild type.

6. adisinsight.springer.com adisinsight.springer.com/trials/700377815

Ask the expert - AdisInsight - Springer A Phase 1/2, First-in-Human, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of RNK08954 in Patients With Advanced ...