GAVRETO is a kinase inhibitor indicated for treatment of:...Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer as detected by an FDA approved test (NSCLC).

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.

Roche...announced that the European Commission (EC) has granted conditional marketing authorisation for Gavreto® (pralsetinib) as a monotherapy for the treatment of adults with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor.

CStone Pharmaceuticals...announces that the National Medical Products Administration (NMPA) of China has approved GAVRETO (pralsetinib) capsules for the treatment of adult patients with locally advanced or metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) after platinum-based chemotherapy.

Overall, the ARROW study showed that pralsetinib was effective in shrinking tumours in patients with RET fusion+ NSCLC regardless of previous treatment history.

We are pleased to see that the NMPA has accepted the company’s NDA for pralsetinib with the priority review designation for the treatment of RET fusion-positive NSCLC patients previously treated with platinum-based chemotherapy.

...Diagnosis during dose expansion (Part 2) – All patients (with the exception of Groups 3, 4 and 9) must have an oncogenic RET fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor, as determined by local or central testing of tumor or circulating tumor nucleic acid in blood; as detailed below. ...

...Pathologically documented and definitively diagnosed non-resectable or metastatic NSCLC with a RET fusion for patients who are either treatment naïve, or who have been previously treated with systemic therapy....

...Diagnosis during dose expansion (Phase 2) – All patients (with the exception of patients with MTC enrolled in Groups 3, 4 and 9) must have an oncogenic RET fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor, as determined by local testing of tumor or circulating tumor nucleic acid in blood; as detailed below. ...

...Patient must meet 1 of the following 2 criteria: a. Have a documented RET fusion using either tissue or plasma as determined by a local test. ...

...- participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion previously treated with a platinum-based chemotherapy....

...- Must have a diagnosis of locally advanced (non-resectable) or metastatic RET-fusion positive NSCLC...

...- Participant must have a documented RET-fusion...

Pralsetinib showed robust and durable clinical activity with a well-tolerated safety profile in Chinese patients with RET fusion-positive NSCLC.

This multicenter, retrospective, real-world data analysis enrolled thirty-one aNSCLC with acquired RET-fusion…Patients who received pralsetinib-based therapy had a longer PFS and TTF compared with patients in cohort 2 (PFS: 8.42 months vs. 6.97 months, TTF: 6.48 months vs. 4.24 months).

With longer follow-up, pralsetinib continues to demonstrate deep and durable response and long-term clinical benefit in RET fusion+ NSCLC Chinese patients with or without prior platinum-based chemotherapy.

62 patients with RET-fusion positive NSCLC received pralsetinib at 20 Italian centers….The objective response rate (ORR) was 66 % [95 % confidence interval (CI), 53-81] in the evaluable population (n = 59). The disease control rate (DCR) was 79 %. After a median follow-up of 10.1 months, the median progression free survival was 8.9 months (95 %CI, 4.7-NA)....In the real-world setting, pralsetinib confirmed durable systemic activity and intracranial response in RET-fusion positive NSCLC.

...281 pts with RET fusion+ NSCLC had received pralsetinib...The ORR was 63.1% in pts with prior platinum treatment and 77.6% in those who were systemic treatment-naïve (Table), consistent with earlier data cuts. Median overall survival was 44.3 months in pre-treated pts and not reached in treatment-naïve pts.

A retrospective efficacy and safety analysis was performed on data from patients with RET fusion positive NSCLC who were enrolled in the pralsetinib Italian expanded access program (EAP)….The objective response rate (ORR) was 66% [95% confidence interval (CI), 53–81] in the evaluable population (n=58). The disease control rate (DCR) was 79%. After a median follow-up of 10.1 months, the median progression free survival was 8.9 months (95% CI, 4.7–NA). In patients with measurable brain metastases (n = 6) intracranial ORR was 83%, and intracranial DCR was 100%....In the real-world setting, pralsetinib confirmed durable systemic activity and intracranial response in RET fusion-positive NSCLC.

Between 17 March 2017 and 06 November 2020 (data cutoff), 281 patients with RET fusion–positive NSCLC were enrolled. The ORR was 72% (54/75; 95% CI, 60–82) for treatment-naïve patients and 59% (80/136; 95% CI, 50–67) for patients with prior platinum-based chemotherapy (enrolment cutoff for efficacy analysis: 22 May 2020)....Pralsetinib treatment produced robust efficacy and was generally well tolerated in treatment-naïve patients with advanced RET fusion–positive NSCLC.

From April 2020, we administered pralsetinib to a total of 10 patients with RET fusion-positive non-small cell lung cancer...Of the nine patients with measurable lesions, seven achieved a partial response. Additionally, one patient without measurable lesions also showed a clinical response.

Roche...today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Gavreto® (pralsetinib) as a monotherapy for the treatment of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor....The CHMP recommendation is based on the results of the phase I/II ARROW study, in which Gavreto demonstrated rapid, potent, and durable clinical activity in patients with advanced RET fusion-positive NSCLC.

Pralsetinib shows high ORRs in Chinese RET fusion+ NSCLC patients regardless of prior therapy….Pralsetinib safety profile in Chinese patients is manageable, with no new safety signals detected. Overall, pralsetinib showed a favorable benefit-risk profile, offering a transformative medicine to Chinese RET-fusion driven advanced NSCLC patients.

RET fusion+ Chinese NSCLC patients without or with prior platinum-based chemotherapy were enrolled and administered with pralsetinib...Pralsetinib shows high ORRs in Chinese RET fusion+ NSCLC patients regardless of prior therapy....Pralsetinib is a promising targeted therapy with rapid and deep clinical activity in RET fusion+ NSCLC Chinese patients regardless of prior therapies.

Of 233 patients with RET fusion-positive NSCLC...Overall responses were recorded in 53...of 87 patients with previous platinum-based chemotherapy, including five (6%) patients with a complete response; and 19...of 27 treatment-naive patients, including three (11%) with a complete response....Pralsetinib is a new, well-tolerated, promising, once-daily oral treatment option for patients with RET fusion-positive NSCLC.

ARROW is a phase 1/2 open-label study conducted at 84 sites in 13 countries. Phase 2 expansion cohorts included patients with RET fusion–positive NSCLC….Pralsetinib showed rapid, potent, and durable clinical activity in patients with RET fusion-positive NSCLC (regardless of prior therapies), including poor prognosis patients not eligible for platinum-based therapy.

This is the first pivotal study to show that pralsetinib has deep and durable antitumor activity, and is well-tolerated in a cohort of Chinese patients with RET fusion+ NSCLC previously treated with platinum-based chemotherapy.

Overall, the data showed that efficacy and safety outcomes in Chinese patients with RET-fusion NSCLC were consistent with previously reported data from the global patient population in the ARROW trial.

54 pts with advanced solid tumors had received pralsetinib at starting dose of 400 mg QD with median follow-up 8.8 months. ORR, disease control rate (DCR), and % of pts with tumor size reduction are shown in the table for pts with metastatic RET fusion+ NSCLC.

...354 pts with advanced solid tumors had received pralsetinib at starting dose of 400 mg QD with median follow-up 8.8 months….ORR was similar regardless of RET fusion partner, prior therapies, or central nervous system involvement. Overall there were 7 (6%) complete responses, 4 (5%) in prior platinum pts and 3 (12%) in treatment naïve pts; median time to response overall was 1.8 months and median duration of response (DOR) was not reached (95% CI, 11.3–NR)....data demonstrate that pralsetinib has rapid, potent, and durable clinical activity in pts with advanced RET fusion+ NSCLC regardless of RET fusion genotype...

As the clinical data for pralsetinib have matured, with deep and durable responses along with robust evidence of activity against brain metastases, our confidence has continued to grow in the potential of pralsetinib to provide lasting benefit to a broad population of patients with RET fusion-positive NSCLC...

Our study demonstrates that pralsetinib is an effective therapeutic option that provides survival benefits for elderly NSCLC patients harboring RET fusion.

One patient acquiring RET fusion after EGFR-TKI resistance received pralsetinib monotherapy and obtained clinic response...Selective RET inhibitors showed durable efficacy compared with cabozantinib for RET fusion NSCLC.