Suzhou-China based Cstone Pharmaceuticals Co. Ltd., which in-licensed RET inhibitor pralsetinib from Blueprint Medicines Corp. in 2018, has won Chinese approval for the drug to treat adult patients with locally advanced or metastatic RET fusion-positive non-small-cell lung cancer (NSCLC) after platinum-based chemotherapy. Already approved as Gavreto in the U.S., the drug is Cstone’s first product approved in China and the country’s first selective RET inhibitor. Cstone said it expects two more drugs to win approval this year.

RET fusions account for 1% to 2% of NSCLC patients. However, though Gavreto targets a very small subset of patients, it could change the standards of care for those with RET fusion-positive NSCLC, who are mostly non-smokers.

The NMPA approval was granted based on a global phase I/II clinical study known as Arrow, evaluating Gavreto’s efficacy and safety in patients with RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer and other advanced solid tumors with RET fusions.

“Data from the Arrow study showed that Gavreto had robust and durable antitumor activity in Chinese patients with advanced or metastatic RET fusion-positive NSCLC after platinum-based chemotherapy,” Cstone said.

The overall response rate was 56% among the Chinese patients, with the median duration of response not reached. The six-month duration of response rate was 83%.

Detailed data were presented at the International Association for the Study of Lung Cancer 2020. Cstone said the efficacy and safety results of pralsetinib at 400 mg once daily from China sites were consistent with previously reported data from the global patient population.

As of a data cutoff date of May 22, 2020, a total of 37 patients with advanced RET fusion-positive NSCLC from 10 China sites were enrolled in the trial. All patients had received at least one platinum-based chemotherapy regimen, with about half having received no fewer than three types of systemic treatments, and 32% having received no fewer than three types of chemotherapy regimens.

In 32 patients, the confirmed overall response rate was 56%, including one complete response and 17 partial responses. The median time to first response was 1.9 months Furthermore, the disease control rate reached 97% and one patient was not evaluable.

More indications to come

Cstone is also studying Gavreto in other indications, including first-line NSCLC, thyroid cancer and other solid tumors. “We plan to release the key results from two first-line studies of pralsetinib in RET fusion-positive NSCLC and RET-mutant medullary thyroid cancer Chinese patients treated without platinum-based chemotherapy this year,” said Cstone’s chief medical officer Jason Yang. “If the results are positive, we will submit new drug applications.”

In December 2020, Gavreto was granted breakthrough therapy designation in China for patients with advanced or metastatic RET-mutant MTC. Cstone filed for an NDA in March for advanced or metastatic RET-mutant MTC and RET fusion-positive thyroid cancer.

Two China approvals ahead

Cstone is next expecting NDA approvals in China for its KIT/PDGFRA inhibitor Ayvakit (avapritinib) and PD-L1 inhibitor sugemalimab, both this year.

The marketing nod for avapritinib could come “imminently”, Cstone said on March 25. If approved, the drug would likely be indicated for adults with unresectable or metastatic gastrointestinal stromal tumor harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. Avapritinib is expected to be China’s first approved precision therapy for such patients. The drug is also expected to be approved in Taiwan in the first half of 2021. As in the U.S. it will be marketed under the brand name Ayvakit.

As with Gavreto, Cstone licensed Greater China rights for avapritinib from Blueprint in June 2018.

Next is sugemalimab, approval of which is expected in the second half of this year. In August 2020, sugemalimab met primary endpoint in a phase III trial as first-line treatment for stage IV squamous and non-squamous NSCLC, for which Cstone said only sugemalimab had proven efficacious among all PD-L1 competitors. The company licensed China rights to the drug to Pfizer in 2020, followed shortly thereafter by a deal providing ex-China rights exclusively to Eqrx Inc.

Another late-stage asset to note of is IDH1 inhibitor Tibsovo (ivosidenib), which Cstone licensed from Agios Pharmaceuticals Inc. – now part of Servier Pharmaceuticals LLC following approval of Servier’s purchase of the company on March 25 – for greater China. Cstone expects to submit an NDA to the NMPA for ivosidenib in the second half of 2021.