General Information

Retevmo (selpercatinib) is a selective and potent RET kinase inhibitor. 

Retevmo is specifically indicated for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), and the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).

Retevmo is supplied as a capsule for oral administration. The recommended dosage of Retevmo based on body weight is:

• Less than 50 kg: 120 mg 
• 50 kg or greater: 160 mg 

Take Retevmo orally twice daily (approximately every 12 hours) until disease progression or unacceptable toxicity. Swallow the capsules whole. Do not crush or chew the capsules. Do not take a missed dose unless it is more than 6 hours until next scheduled dose.  If vomiting occurs after Retevmo administration, do not take an additional dose and continue to the next scheduled time for the next dose. 

Mechanism of Action

Retevmo (selpercatinib) is an orally bioavailable selective inhibitor of wild-type, mutant and fusion products involving the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET), with potential antineoplastic activity. Upon oral administration, selpercatinib selectively binds to and targets various RET mutants and RET-containing fusion products. This results in an inhibition of cell growth of tumors cells that exhibit increased RET activity. RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types; dysregulation of RET activity plays a key role in the development and progression of these cancers.

Side Effects

Adverse effects associated with the use of Retevmo may include, but are not limited to, the following:

• laboratory abnormalities
• dry mouth
• diarrhea
• increased creatinine
• increased alkaline phosphatase
• hypertension
• fatigue
• edema
• decreased platelets
• increased total cholesterol
• rash
• decreased sodium
• constipation

Clinical Trial Results

Retevmo was approved under accelerated approval based on overall response rate and duration of response. Continued approval for each indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

Accelerated Approval was based on the LIBRETTO-001 Phase 1/2 trial's endpoints of objective response rate (ORR) and duration of response (DoR). The single-arm, multi-center Phase 1/2 trial enrolled 702 patients with RET-driven cancers. The trial enrolled both treatment-naive patients and heavily pretreated patients with a variety of advanced solid tumors including RET fusion-positive NSCLC, RET-mutant MTC, RET fusion-positive thyroid cancer, and certain other solid tumors with RET alterations. Results are as follows:

RET Fusion-Positive NSCLC:

• Systemic Treatment Naïve Patients: ORR 85% and median DoR not reached at time of analysis.
• Treatment Experienced Patients: ORR 64% and median DoR 17.5 months.

RET-Mutant MTC:

• Cabozantinib/Vandetanib Naïve Patients: ORR 73% and median DoR 22 months
• Cabozantinib/Vandetanib Experienced Patients: ORR 69% and median DoR not reached at time of analysis.

RET Fusion-Positive Thyroid Cancers:

• Systemic Treatment Naïve patients: ORR 100% and median DoR not reached at time of analysis.
• Treatment Experienced Patients: ORR 79% and median DoR 18.4  months.