Phase 3 Study of RMC-6236 in Patients with Previously Treated Metastatic PDAC

JRCT ID: jRCT2031240614

Registered date:16/01/2025

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Pancreatic Ductal Adenocarcinoma
• Date of first enrollment: 01/03/2025
• Target sample size: 42
• Countries of recruitment: USA,Japan,Italy,Japan,Spain,Japan,Germany,Japan,France,Japan
• Study type: Interventional

Intervention(s)

<Phase 3 part>
Patient will be randomized in a 1:1 ratio to receive RMC-6236 (Arm A) or Investigator's choice of standard of care chemotherapy (Arm B).
[Arm A]
RMC-6236 will be administered orally at a dose of 300 mg once daily.

[Arm B]
Gemcitabine plus nab-paclitaxel (GnP): In 28-day cycle, administer the following on Day 1, 8, and 15.
Gemcitabine: 1000 mg/m2 intravenous (IV) over 30 minutes
Nab-paclitaxel: 125 mg/m2 IV over 30 minutes

mFOLFIRINOX: In 28-day cycle, administer the following on Day 1 and 15.
Oxaliplatin: 85 mg/m2 IV over 2 hours
Leucovorin: (calcium folinate/folinic acid): 400 mg/m2 IV over 2 hours after oxaliplatin
Irinotecan: 150 mg/m2 IV over 90 minutes concurrent with last 90 minutes of leucovorin infusion
5-fluorouracil: 2400 mg/m2 IV continuous over 46 hours (or 1200 mg/m2/day)

Nal-IRI+5-FU/LV: In 28-day cycle, administer the following on Day 1 and 15.
Liposomal irinotecan: 70 mg/m2 IV over 90 minutes
Leucovorin (calcium folinate/folinic acid): 400 mg/m2 IV over 30 minutes
5-fluorouracil: 2400 mg/m2 IV continuous over 46 hours (or 1200 mg/m2/day)

FOLFOX: In 28-day cycle, administer the following on Day 1 and 15.
Oxaliplatin: 85 mg/m2 IV over 2 hours
Leucovorin (calcium folinate/folinic acid): 400 mg/m2 IV over 2 hours concurrent with oxaliplatin
5-fluorouracil: 400 mg/m2 bolus immediately after leucovorin and 2400 mg/m2 IV continuous over 46 hours (or 1200 mg/m2/day) after IV bolus

<Japanese Safety Run-in Cohort>
Administer RMC-6236 orally at a dose of 300 mg once daily.

Outcome(s)

Primary Outcome

To compare the effect of treatment with RMC-6236 versus Investigator's choice of standard therapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).
In Japanese Safety Run-in Cohort, to evaluate the safety and tolerability of RMC-6236 monotherapy in Japanese patients with metastatic PDAC

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

At least 18 years old and has provided informed consent.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Histologically or cytologically confirmed PDAC with metastatic disease.
Measurable disease per RECIST 1.1.
Adequate organ function (bone marrow, liver, kidney, coagulation)
Documented RAS mutation status, either mutant or wild-type. Eligible RAS mutations defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).
Able to take oral medications.Able to take oral medications.Able to take oral medications.

Exclude criteria

Prior therapy with direct RAS-targeted therapy (eg. degraders and/or inhibitors).
History of or known central nervous system metastatic disease.
Any conditions that may affect the ability to take or absorb study treatment
Major surgery within 4 weeks prior to randomization.
Patient is unable or unwilling to comply with protocol-required study visits or procedures

Related Information

• Primary Sponsor: Zeena Salman
• Secondary ID(s): NCT06625320