RNK08954 treatment for metastatic pancreatic ductal adenocarcinoma with KRAS G12D mutation

A Study to Evaluate the Efficacy and Safety of RNK08954 in Subjects With KRAS G12D-Mutated Metastatic Pancreatic Ductal Adenocarcinoma

This study tests whether RNK08954 is safe and helps people with metastatic pancreatic ductal adenocarcinoma who have a KRAS G12D mutation.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ranok Therapuetics Co. Ltd. (Industry-sponsored)
• Locations: 2 sites (Nanjing and 1 other locations)
• Trial ID: NCT07303465 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label phase IIa trial giving RNK08954 to adults with metastatic pancreatic ductal adenocarcinoma harboring a KRAS G12D mutation to explore safety, tolerability, and early signs of anti-tumor activity. Eligible participants are 18–75 years old with pathology‑confirmed PDAC, at least one measurable lesion per RECIST 1.1, ECOG 0–1, and adequate hematologic and organ function. The study is conducted at sites in Nanjing and Shanghai and follows patients for adverse events, tolerability, and tumor response measures. Dosing and assessment schedules are defined in the protocol and focus on preliminary efficacy signals alongside safety data.

Who should consider this trial

Good fit: Adults aged 18–75 with metastatic PDAC confirmed by pathology, a documented KRAS G12D mutation, at least one measurable lesion, ECOG performance status 0–1, and adequate blood and organ function are ideal candidates.

Not a fit: Patients without a KRAS G12D mutation, those with poor performance status (ECOG ≥2), insufficient organ function, or expected survival under 12 weeks are unlikely to receive benefit from this study.

Why it matters

Potential benefit: If successful, RNK08954 could provide a targeted treatment option that slows tumor growth and extends disease control for patients with KRAS G12D–mutant metastatic pancreatic cancer.

How similar studies have performed: Directly targeting KRAS G12D is a relatively new approach with limited clinical data so far, while KRAS G12C inhibitors have shown success in other cancers but do not apply to G12D.

Eligibility criteria

Inclusion Criteria:

* The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up.
* Male and female subjects aged 18-75 years (including 18 and 75 years).
* Pancreatic ductal adenocarcinoma confirmed by pathology (histology) or cytology.
* At the time of study enrollment, according to the solid tumor efficacy evaluation criteria (RECIST1.1), imaging diagnosis had at least one measurable lesion .
* Presence of a KRAS G12D mutation.
* Physical condition score ECOG score 0-1 points.
* Expected survival ≥ 12 weeks.
* Have adequate hematologic and end-organ function, with laboratory test results within required parameters within 7 days prior to the first dose.
* Fertile female subjects and male subjects whose partners are women of reproductive age must agree to comply with the contraceptive requirement from the time of signing the informed consent until 6 months after the final administration of the trial drug.Fertile female subjects must undergo a serum pregnancy test within 7 days before the first dose, and the result is negative; And must be non-lactating.

Exclusion Criteria:

* Diagnosed with other pathological types of pancreatic tumors;
* Presence of uncontrolled symptomatic central nervous system metastases; including leptomeningeal metastasis, spinal cord metastasis, or brainstem metastasis.
* Presence of symptomatic, moderate or greater fluid accumulation in serous cavities (e.g., pleural effusion, ascites, pericardial effusion) which either necessitates therapeutic intervention or is judged by the investigator to make the patient ineligible.
* Clinical condition with an acute and significant decline, including, but not limited to, a decrease in ECOG performance status to \>1 within 72 hours prior to the baseline visit and initiation of study treatment, a weight loss of ≥10% during the screening period, or a BMI \<18.0 kg/m²
* Except for certain circumstances, a history of malignant tumors other than the inclusion diagnosis within 2 years prior to the first administration of the drug;
* History of known severe or uncontrolled cardiovascular or cerebrovascular disease that requires treatment.
* The patient had previously used KRAS inhibitors or pan-KRAS inhibitors therapy.
* Received systemic anti-tumor therapy prior to the first dose, or received Chinese herbal preparations with clear anti-pancreatic tumor indications within 2 weeks before the first dose.
* Having received other investigational drugs or therapies not yet approved for marketing prior to the first dose, with the interval from the last administration or treatment being less than 4 weeks or 5 half-lives (whichever is shorter).
* Having undergone major surgery or experienced significant trauma within 4 weeks prior to the first dose, or requiring elective surgery during the trial period.
* The presence of severe non-healing wounds, ulcers, fractures, etc., within 4 weeks prior to the first dose.
* Severe infection occurred within 4 weeks prior to the first dose, including but not limited to hospitalization due to infectious complications, bacteremia, or severe pneumonia; presence of systemic active infection within 2 weeks prior to the first dose requiring systemic anti-infective therapy.
* Presence of active tuberculosis infection at the time of screening.
* Positive for hepatitis B surface antigen (HBsAg) at screening with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 2000 IU/mL or 10⁴ copies/mL (however, subjects can be enrolled if their HBV-DNA is \<2000 IU/mL or 10⁴ copies/mL after antiviral therapy).
* Positive for hepatitis C antibody (HCV-Ab) and positive for hepatitis C virus (HCV) ribonucleic acid (RNA) at screening.
* Known infection with human immunodeficiency virus (HIV) or active Treponema pallidum, except under certain circumstances.
* Presence of any toxicity from previous antitumor therapies that has not recovered to Grade ≤1.
* Other situations that the researchers believe should not be included.

Where this trial is running

Nanjing and 1 other locations

• Nanjing Tianyinshan Hospital — Nanjing, China (Recruiting)
• Shanghai GoBroad Cancer Hospital China Pharmaccutical University — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: ShuKui Qing, MD — Nanjing Tianyinshan Hospital
• Study coordinator: Xin Wu

Conditions KRAS G12D Mutations; Pancreatic Ductal Adenocarcinoma