Drug Update · Oncology

FDA Approves Selpercatinib for RET Fusion Solid Tumors: ORR 47%

September 12, 2026

Approval date

07/14/2026

Indication

Locally advanced or metastatic solid tumors with a RET gene fusion in adults and pediatric patients 2 years and older who progressed on or after prior systemic treatment or have no satisfactory alternative treatment options

Primary efficacy (other tumors)

ORR 47% (95% CI: 35, 59) in 75 patients (LIBRETTO-001) [4]

Median duration of response

24.5 months (95% CI: 11.2, 49.1) [4]

Clinical Perspective

This approval affects oncologists, pediatric oncologists, and multidisciplinary cancer teams treating adult and pediatric patients 2 years of age and older with locally advanced or metastatic RET fusion-positive solid tumors ^[3]^[1]. The source‑confirmed data support use of selpercatinib in patients with RET gene fusions detected by an FDA‑approved test when disease has progressed on or following prior systemic treatment or when no satisfactory alternative treatment options exist ^[3]^[1]. How selpercatinib should be sequenced with other RET-directed therapies and integrated across specific tumor histologies remains to be defined in broader clinical practice and ongoing studies?

Dr. Rahul Verma, MBBS, MD (General Medicine), DM (Medical Oncology) · Oncology

On July 14, 2026 the Food and Drug Administration granted traditional approval to selpercatinib (Retevmo, Eli Lilly and Company) for adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options ^[3]^[2]. The approval was based in part on efficacy data from LIBRETTO-001 showing an overall response rate (ORR) of 47% and a median duration of response (DOR) of 24.5 months in 75 patients with RET fusion-positive tumors other than NSCLC and thyroid cancer ^[3].

Clinical Context

Selpercatinib (Retevmo) is a small-molecule kinase inhibitor that targets RET and is manufactured by Eli Lilly and Company; the product is available as capsules and tablets per the prescribing information ^[1]^[5]. The July 14, 2026 regulatory action converted prior accelerated approvals for the indication in adult and pediatric patients to traditional approval for locally advanced or metastatic RET fusion-positive solid tumors that progressed following prior systemic therapy or when no satisfactory alternative exists ^[2]^[3]. The agent’s approval requires selection of patients whose tumors harbor a RET gene fusion as detected by an FDA‑approved test; information on FDA‑approved tests is referenced in the prescribing information ^[1]^[5]. The approval decision referenced data from multicenter, open‑label, multi‑cohort trials including LIBRETTO-001 (adults) and supportive pediatric data from LIBRETTO-121 ^[3]^[5].

Key Findings

Selpercatinib (Retevmo) achieved an overall response rate (ORR) of 47% (95% CI: 35, 59) in 75 patients with RET fusion-positive solid tumors other than non‑small cell lung cancer and thyroid cancer enrolled in LIBRETTO-001; the median duration of response was 24.5 months (95% CI: 11.2, 49.1) ^[3].
Efficacy supporting the approval also included results in RET fusion-positive NSCLC and RET fusion-positive thyroid cancer cohorts from LIBRETTO-001 and supportive pediatric responses observed in LIBRETTO-121; pediatric and young adult responses included durable responses in RET‑mutant medullary thyroid cancer and RET fusion-positive thyroid cancer per FDA summary ^[3]^[4]^[5].

Safety & Tolerability

Hepatotoxicity: monitor ALT and AST prior to initiating therapy, every 2 weeks during the first 3 months, then monthly thereafter; withhold, reduce dose, or permanently discontinue based on severity ^[1].
Clinicians should consult current prescribing information for full dosing guidance.
Interstitial lung disease/pneumonitis: monitor for new or worsening pulmonary symptoms and withhold, reduce dose, or permanently discontinue based on severity ^[1].
Hypertension: do not initiate in uncontrolled hypertension; monitor blood pressure after 1 week and at least monthly thereafter and take dose actions per severity ^[1].
QT interval prolongation: assess QT, electrolytes and TSH at baseline and periodically; monitor more frequently with concomitant strong or moderate CYP3A inhibitors or other QT‑prolonging drugs ^[1].
Hemorrhagic events: permanently discontinue for severe or life‑threatening hemorrhage ^[1].
Hypersensitivity: withhold and initiate corticosteroids; resume at reduced dose with steroid taper per labeling ^[1].
Tumor lysis syndrome: closely monitor patients at risk and treat as clinically indicated ^[1].
Risk of impaired wound healing: withhold at least 7 days prior to elective surgery and do not administer for at least 2 weeks following major surgery until adequate wound healing ^[1].
Hypothyroidism: monitor thyroid function before and periodically during treatment; withhold or discontinue based on severity ^[1].
Embryo-fetal toxicity: can cause fetal harm; advise females of reproductive potential to use effective contraception ^[1].
Slipped capital femoral epiphysis/slipped upper femoral epiphysis (SCFE/SUFE) in pediatric patients: monitor for symptoms and treat as medically and surgically appropriate ^[1].
The most common adverse reactions (≥25%) reported in adults with solid tumors included musculoskeletal pain, edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, rash, nausea, constipation, cough, headache, vomiting, dyspnea, and hemorrhage ^[1].

Study Design

The FDA based its decision on efficacy and safety data from multicenter, open‑label, multi‑cohort trials. Efficacy for the non‑NSCLC/non‑thyroid solid tumor population was evaluated in 75 patients enrolled in LIBRETTO-001 (NCT03157128) with major outcome measures of ORR and DOR assessed by blinded independent review ^[3]^[5]. Pediatric efficacy was evaluated in LIBRETTO-121, an international, open‑label, multi‑cohort pediatric trial supporting responses in pediatric and young adult patients ^[3]^[4]^[5]. The conversion to traditional approval and fulfillment of postmarketing requirements is documented in the FDA approval letter effective July 14, 2026 ^[2].

FAQ

Q1 What is selpercatinib (Retevmo) approved for?

Selpercatinib (Retevmo) is approved for the treatment of adult patients with locally advanced or metastatic non‑small cell lung cancer with a RET gene fusion, adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer with a RET mutation who require systemic therapy, adult and pediatric patients 2 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion who require systemic therapy and who are radioactive iodine‑refractory (if radioactive iodine is appropriate), and adult and pediatric patients 2 years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.

Q2 How does selpercatinib work?

Selpercatinib is a kinase inhibitor that inhibits wild‑type RET and multiple mutated RET isoforms; it demonstrated anti‑tumor activity in tumors harboring constitutively activated RET proteins resulting from gene fusions and mutations in preclinical models and clinical trials. The prescribing information describes RET inhibition as the mechanism of action and notes activity against certain RET fusion proteins and mutations.

Q3 What is the recommended dose of selpercatinib?

The recommended dose for adult and adolescent patients 12 years of age or older is weight‑based: patients less than 50 kg receive 120 mg orally twice daily and patients 50 kg or greater receive 160 mg orally twice daily. Pediatric dosing for patients 2 to less than 12 years is based on body surface area with specific dose tiers described in the prescribing information; dosing is continued until disease progression or unacceptable toxicity. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of selpercatinib?

The most common adverse reactions (≥25%) in adults with solid tumors included musculoskeletal pain, edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, rash, nausea, constipation, cough, headache, vomiting, dyspnea, and hemorrhage. Labeling also includes warnings and precautions for hepatotoxicity, interstitial lung disease/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor lysis syndrome, impaired wound healing, hypothyroidism, embryo‑fetal toxicity, and slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Selpercatinib for RET Fusion Solid Tumors: ORR 47%

Direct Clinical Takeaway & Evidence Summary

FDA Approves Selpercatinib for RET Fusion Solid Tumors: ORR 47%

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Cite & Reference This Monograph

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