Table of contents

• Trial overview
• Non-small cell lung cancer studies
• Thyroid cancer studies
• Pediatric and other solid tumor studies
• Expanded access and precision medicine programs
• Main endpoints and what they mean
• Who can participate

Trial overview

The trial data show that Selpercatinib is being studied in several clinical trial settings, mainly for cancers with RET alterations.^[1][2][3]

The studies include Phase 1, Phase 1/2, Phase 2, and Phase 3 trials, plus an expanded access program that is meant to provide access rather than test a formal endpoint.^[2][5]

Most trials focus on people with advanced, locally advanced, or metastatic cancer, and many require evidence of a RET change in the tumor or blood.^[1][3][5]

Non-small cell lung cancer studies

One major Phase 3 study, LIBRETTO-431, compares Selpercatinib with platinum-based therapy plus pemetrexed, with or without pembrolizumab, in patients with advanced or metastatic RET fusion-positive non-small cell lung cancer.^[1]

The main goal is to compare progression-free survival, which means the time before the cancer gets worse.^[1]

Another Phase 3 study, LIBRETTO-432, tests Selpercatinib against placebo after surgery in people with stage II-IIIA RET fusion-positive NSCLC.^[4]

This study measures event-free survival, which is the time before the cancer returns, worsens, or another important event happens.^[4]

Thyroid cancer studies

Selpercatinib is also being studied in RET-mutant medullary thyroid cancer in a Phase 3 trial that compares it with cabozantinib or vandetanib.^[4]

This study looks at progression-free survival by blinded central review, meaning the scans are checked by experts who do not know which treatment the patient received.^[4]

The trial includes patients with progressive, advanced disease who have not previously received a kinase inhibitor, which is a type of targeted cancer treatment.^[4]

Pediatric and other solid tumor studies

A Phase 1/2 study includes children and teenagers with advanced RET-altered solid tumors or primary central nervous system tumors.^[2]

In Phase 1, the study checks safety, including dose-limiting toxicities, which are side effects serious enough to limit treatment.^[2]

In Phase 2, the study measures overall response rate, meaning the percentage of patients whose tumors shrink or disappear.^[2]

Another large Phase 1/2 study includes patients age 12 years or older with locally advanced or metastatic solid tumors that show a RET gene alteration in the tumor and/or blood.^[3]

Its Phase 1 part looks for the maximum tolerated dose and the recommended Phase 2 dose, while Phase 2 measures response by RECIST 1.1 or RANO, depending on the tumor type.^[3]

Expanded access and precision medicine programs

The LIBRETTO-201 expanded access program gives Selpercatinib to adults with locally advanced or metastatic solid tumors with activating RET alterations.^[5]

This program lists several tumor types, including non-small cell lung cancer, medullary thyroid cancer, colon cancer, breast cancer, pancreatic cancer, papillary thyroid cancer, and other solid tumors with activating RET alterations.^[5]

The program does not have endpoints or data analysis, so it is different from a standard efficacy trial.^[5]

Selpercatinib also appears in a Phase 2 precision medicine study in advanced pancreatic cancer, where treatment is matched to molecular findings and compared with standard care.^[7]

That study measures progression-free survival.^[7]

Main endpoints and what they mean

The trial data use several common endpoints, or main results that researchers want to measure.^{[1][2][3][4][7]}

• Progression-free survival: time without the cancer getting worse.^[1][4][7]

• Overall response rate: how many patients have a tumor response, such as complete response or partial response.^[2][3]

• Event-free survival: time before the cancer returns or another important event occurs after treatment.^[4]

• Dose-limiting toxicities and other safety outcomes: side effects that may limit treatment or show how safe the study treatment is.^[2]

• Disease control: in the DRUP trial, this means stable disease at 16 weeks after treatment starts.^[6]

Some studies also use blinded independent review or independent review committees to judge scans and responses in a more objective way.^[1][2][3][4]

Who can participate

Eligibility depends on the specific trial and cancer type.^{[1][2][3][4][5][7]}

Some studies include adults only, such as the expanded access program, while others include children, teenagers, or people age 12 years and older.^[2][3][5]

Many trials require advanced, metastatic, or locally advanced disease, and several require a RET fusion or another RET alteration in the tumor or blood.^{[1][2][3][4][5]}