On Tuesday, the MFDS approved Roche’s Gavreto to treat adult patients with RET fusion-positive locally advanced or metastatic NSCLC and adult patients with RET-mutated locally advanced or metastatic medullary thyroid cancer requiring systemic therapy....The permits for the two therapies were based on their response rates and duration of response in phase 1/2 trials.

Thyroid Carcinoma - Medullary Carcinoma: Preferred Regimens...Pralsetinib (RET mutation-positive)

CStone Pharmaceuticals...announces that the National Medical Products Administration (NMPA) of China has accepted the New Drug Application (NDA) of selective inhibitor GAVRETO (Pralsetinib) with priority review designation for the treatment of the patients with advanced or metastatic RET-altered thyroid cancer...This NDA acceptance is based on efficacy and safety results from the global Phase 1/2 ARROW trial designed to evaluate pralsetinib in RET-mutant MTC.

FDA also granted Priority Review to Gavreto for the treatment of people with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer

...Pathologically documented and definitively diagnosed RET mutation in advanced MTC patients who are treatment naïve or who have been previously treated with MKI therapy, or 1c....

...- participants must have a pathologically documented, definitively diagnosed advanced solid tumor with an oncogenic RET fusion or mutation that was previously treated with a selective tyrosine kinase inhibitor (TKI) that inhibits RET...

...- Confirmed RET mutation....

In pts with RET-mutant MTC who had received prior C/V (n = 67), ORR was 51% (34/67; 95% CI 38–63; 2 complete responses [CR]; 32 partial responses [PR]), median duration of response (DoR) was 25.8 months...In this updated analysis including more pts, pralsetinib continues to be efficacious with a manageable safety profile in pts with RET-altered TC.

CStone Pharmaceuticals (CStone, HKEX: 2616)...today announced positive results from China registrational study of the global pivotal Phase 1/2 ARROW clinical trial of the RET inhibitor GAVRETO® (pralsetinib), showing deep and durable anti-tumor activity in Chinese patients with advanced or metastatic RET-mutant- MTC.

Among patients with baseline measurable disease who received pralsetinib...overall response rates were 15 (71%) of 21 (95% CI 48–89) in patients with treatment-naive RET-mutant medullary thyroid cancer and 33 (60%) of 55 (95% CI 46–73) in patients who had previously received cabozantinib or vandetanib, or both...

Pralsetinib demonstrated potent and durable clinical activity in RET+ MTC regardless of prior treatment with approved multikinase inhibitors or RET-mutation and was well tolerated.…ORR was 65% (95% CI 53–75; n=51/79, 5% complete response [CR]; 59% partial response [PR; 1 pending confirmation])...

In 79 REP with RET+ MTC (mutation: 61% M918T, 28% C634X, 4% V804X, 8% other), ORR was 65% (95% CI 53–75; n=51/79, 5% complete response...Pralsetinib demonstrated potent and durable clinical activity in RET+ MTC regardless of prior treatment with approved multikinase inhibitors or RET-mutation and was well tolerated.

In 79 REP with RET+ MTC (mutation: 61% M918T, 28% C634X, 4% V804X, 8% other)...Responses occurred regardless of RET genotypes (somatic or germline), including 5 of 6 pts with V804X gatekeeper mutation. Pralsetinib demonstrated potent and durable clinical activity in RET+ MTC regardless of prior treatment with approved multikinase inhibitors or RET-mutation and was well tolerated.

In first-in-human testing, BLU-667 significantly inhibited RET signaling and induced durable clinical responses in patients with RET-altered NSCLC and MTC without notable off-target toxicity, providing clinical validation for selective RET targeting.

Pralsetinib is a potent and selective RET inhibitor that targets RET alterations, including fusions and mutations, regardless of the tissue of origin…74% ORR in treatment naïve RET-mutated MTC and 60% ORR+ in those previously treated…Pralsetinib has broad and durable antitumor activity with multiple advanced solid tumor types.