In short
Clinical trials are investigating Selpercatinib in several cancer types, including lung cancer, thyroid cancer, pediatric solid tumors, and other RET-altered cancers. These studies look at safety, how well the treatment works, and which patients may benefit most. Some trials compare Selpercatinib with standard care, while others study it in special groups or access programs.
Key points
- Clinical trials of Selpercatinib are studying several cancers, especially RET fusion-positive non-small cell lung cancer and RET-mutant medullary thyroid cancer. The research also includes pediatric patients with RET-altered solid or brain tumors and adults with other advanced solid tumors that have RET changes. The trial phases range from Phase 1, which focuses on safety and dose, to Phase 3, which compares Selpercatinib with standard treatments or placebo. Main outcomes include progression-free survival, event-free survival, objective response rate, and safety. Some studies test Selpercatinib alone, while others compare it with chemotherapy, pembrolizumab, cabozantinib, vandetanib, or placebo.
Clinical trials overview
These studies are testing Selpercatinib in people with cancers that have RET changes, which are gene changes that may help drive tumor growth. The trials include adults, children, and teenagers, depending on the study. The phases range from Phase 1 to Phase 3, so the research includes early safety studies and later comparison studies.
Lung cancer studies
One Phase 3 study, LIBRETTO-431, compares Selpercatinib with platinum-based therapy, pemetrexed, and with or without pembrolizumab in advanced or metastatic RET fusion-positive non-small cell lung cancer. The main endpoint is progression-free survival, which means how long the cancer stays from getting worse.
Another Phase 3 study, LIBRETTO-432, looks at adjuvant Selpercatinib in stage II-IIIA RET fusion-positive NSCLC after surgery and compares it with placebo. Its main endpoint is event-free survival, which measures how long patients stay free from a cancer-related event such as recurrence or worsening.
The Phase 1/2 study in advanced solid tumors also includes people age 12 years or older with a RET gene alteration in the tumor or blood, and it measures safety first and then tumor response. In Phase 2, the study looks at objective response rate, meaning how many tumors shrink or disappear.
Thyroid cancer studies
A Phase 3 trial is comparing Selpercatinib with cabozantinib or vandetanib in progressive, advanced, kinase inhibitor-naive RET-mutant medullary thyroid cancer. The main endpoint is progression-free survival by blinded independent central review, which means experts who are not part of the treatment team review the scans and results.
Pediatric and solid tumor studies
The pediatric Phase 1/2 study includes children with advanced RET-altered solid tumors or primary central nervous system tumors. Phase 1 checks the frequency, severity, and relatedness of treatment-emergent adverse events and serious adverse events, including dose-limiting toxicities. A dose-limiting toxicity is a side effect that is serious enough to stop dose increases or limit treatment.
In Phase 2 of that pediatric study, the main goal is objective response rate, using RECIST 1.1 or RANO depending on tumor type. RECIST is a method for measuring solid tumors on scans, while RANO is used for brain tumors and other nervous system tumors.
Access and precision medicine studies
The LIBRETTO-201 expanded access program gives access to Selpercatinib for adults with locally advanced or metastatic solid tumors that have activating RET alterations. This study does not have endpoints or data analysis because it is an expanded access program, not a standard efficacy trial.
Two large precision medicine studies also list Selpercatinib among many targeted treatments. One is in cancer patients in Norway and looks at whether treatment matches the molecular tumor profile and at serious treatment-related adverse events. The other is the DRUP trial, which studies several tumor types and measures tumor response, disease control, and treatment-related grade 3 or higher and serious adverse events.
Trial endpoints and measures
Across the Selpercatinib trials, the most important endpoints are progression-free survival, event-free survival, objective response rate, and safety measures such as serious adverse events and dose-limiting toxicities.
Some trials compare Selpercatinib with standard treatment, such as chemotherapy or other targeted drugs, while others compare it with placebo or study it in access programs.