Daraxonrasib

RASONQUE is indicated for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy. RASONQUE is an inhibitor of the RAS GTPase family, indicated for the treatment of adult patients with metastatic pancreatic adenocarcinoma who have received at least one prior systemic therapy or who are not candidates for multiagent systemic therapy.

Daraxonrasib is an inhibitor of the RAS GTPase family. Daraxonrasib binds to cyclophilin A, resulting in a binary complex that binds to the active, GTP-bound state of RAS. The tri-complex inhibits RAS signaling by blocking interactions with downstream effectors and promoting GTP hydrolysis to the inactive GDP-bound state of RAS. Daraxonrasib inhibition of wild-type and mutant variants of KRAS, NRAS, and HRAS induces tumor growth suppression and apoptosis. In RAS-dependent models of pancreatic adenocarcinoma, daraxonrasib treatment led to tumor growth inhibition and regression and is associated with antitumor immunity.

Recommended dosage: 300 mg orally once daily. Swallow tablets whole with or without food. Administer prophylactic and concomitant medications to reduce the risk of dermatologic reactions.

None. None.

Dermatologic and Soft Tissue Toxicity: RASONQUE can cause dermatologic or soft tissue toxicities, including rash, pruritus, and dry skin. Advise patients to limit sun exposure, use sunscreen, and use emollient creams. Withhold, reduce the dose, or permanently discontinue based on severity. Stomatitis and Oral Disorders: RASONQUE can cause stomatitis, including mouth ulcers and oral mucositis. Diarrhea: RASONQUE can cause diarrhea. Gastrointestinal Perforation: Monitor for gastrointestinal perforation. Withhold if suspected. If appropriate, reduce the dose or permanently discontinue if no other potential causes of gastrointestinal perforation are identified. Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms. If appropriate, reduce the dose or permanently discontinue if no other potential causes of ILD/pneumonitis are identified.

The following clinically significant adverse reactions are described elsewhere in the labeling: Dermatologic and Soft Tissue Toxicity Stomatitis and Oral Disorders Diarrhea Gastrointestinal Perforation Interstitial Lung Disease (ILD)/Pneumonitis Most common adverse reactions (≥ 20%) were rash, diarrhea, stomatitis, nausea, fatigue, vomiting, abdominal pain, edema, decreased appetite, and hemorrhage. Most common laboratory abnormalities (≥ 20%) were decreased albumin, decreased calcium, decreased hemoglobin, increased aspartate aminotransferase, decreased lymphocytes, decreased platelets, increased alanine aminotransferase, decreased sodium, decreased white blood cells, decreased magnesium, increased alkaline phosphatase, increased creatinine, and decreased potassium.

Strong CYP3A Inhibitors with P-gp Inhibition: Avoid concomitant use. Strong CYP3A Inhibitors without P-gp Inhibition: Reduce RASONQUE dosage. Moderate CYP3A Inhibitors with or without P-gp Inhibition: Reduce RASONQUE dosage. P-gp Inhibitors: Reduce RASONQUE dosage. Cyclosporine A: Avoid concomitant use. Strong CYP3A Inducers: Avoid concomitant use. Increase RASONQUE dosage if concomitant use cannot be avoided. Moderate CYP3A Inducers: Increase RASONQUE dosage. P-gp Substrates: Take at least 4 hours apart from RASONQUE.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).