2021 ASCO | CStone's selective RET inhibitor pratinib demonstrates long-lasting clinical activity in patients with metastatic RET fusion non-small cell lung cancer and advanced solid tumors

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The American Society of Clinical Oncology (ASCO) annual meeting is the world's largest, highest academic, and most authoritative clinical oncology conference.
Many international cutting-edge and highly-regarded clinical oncology research results and clinical data are unveiled at this conference.

ASCO 2021 will be held in the form of an online virtual meeting on June 4-8, 2021.

A few days ago, the official website of the ASCO annual meeting officially announced the summary of the conference.

It is worth noting that the latest results of the Phase I/II ARROW clinical study of pratinib, a selective RET inhibitor of CStone Pharmaceuticals, were unveiled.

The results of the study show that pratinib has brought lasting clinical benefits to patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) and other advanced solid tumors.

Pratinib has shown a high remission rate in newly treated RET fusion-positive NSCLC patients, and has shown clinical activity in a variety of RET fusion tumor patients, and the safety characteristics of the study are consistent with the results of the previously published ARROW study.

Relevant detailed data will be published at the 2021 ASCO Annual Meeting from June 4 to 8, 2021.

Pratinib is an oral, once-a-day, potent and highly selective RET inhibitor.
At present, the China National Medical Products Administration ("National Medical Products Administration") has approved it to be marketed under the trade name Pugeta®.
In the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer who have previously received platinum-containing chemotherapy for transfection rearrangement (RET) gene fusion positive.

Its application for extended indications has been accepted by the State Food and Drug Administration and has been included in priority review.
The extended indications include advanced or metastatic transfection rearrangement (RET) gene mutation medullary thyroid carcinoma (MTC) that requires systemic treatment.
, And advanced or metastatic RET fusion-positive thyroid cancer (TC) that requires systemic treatment and is refractory to radioactive iodine (if radioactive iodine is appropriate).

Previously, the U.
S.
Food and Drug Administration (FDA) approved it to be marketed under the trade name GAVRETO™ for the treatment of adult patients with metastatic RET fusion-positive NSCLC confirmed by the FDA-approved test method and those in need of systemic treatment.
Adults with advanced or metastatic RET-mutated medullary thyroid cancer and children 12 years and older, as well as adults with advanced or metastatic RET fusion-positive thyroid cancer and children 12 years and older who require systemic treatment and are refractory to radioiodine (if applicable) patient.

The latest research data of pratinib released by ASCO comes from a clinical study called ARROW, which is a global phase I/II clinical study aimed at evaluating pratinib in RET fusion-positive NSCLC The safety, tolerability and efficacy of RET mutant medullary thyroid carcinoma (MTC) and other advanced solid tumors fused with RET.

As of the data deadline (November 6, 2020), a total of 216 patients with RET fusion-positive NSCLC who received 400 mg of pratinib once a day and 19 patients with RET fusion solid tumors were included in the data released by ASCO researching.

 Data on RET fusion-positive NSCLC The median follow-up period of pratinib was 17.
1 months, and showed long-lasting clinical benefit in RET fusion-positive NSCLC patients who received or did not receive treatment.

Among 68 newly treated patients, the overall response rate (ORR) was 79% (95% CI: 68%, 88%).

The complete response (CR) rate was 6%, 10% of patients had complete regression of the target tumor, and 74% of patients had a partial response (PR).

The median time to response (mDOR) was not reached (95%CI: 9.
0 months, not reached).

For patients who have not received treatment, the initial research plan restricts the enrollment of researchers to the researcher's determination to be unsuitable for standard platinum-based chemotherapy, which may be caused by age, comorbidities or other poor prognostic factors.

This qualification restriction was lifted in July 2019, and its goal is to enable more people to reflect the practice in real life.

In an exploratory analysis of patients who did not receive treatment after the expansion of the inclusion criteria (n = 25), the ORR was 88% (95% CI: 69%, 98%), and all responses were PR.

Among the 126 patients who had previously received platinum-based chemotherapy, the ORR was 62% (95% CI: 53%, 70%).

The CR rate was 4%, 12% of the target tumors completely resolved, and 58% of the PR patients.

The median DOR was 22.
3 months (95% CI: 15.
1 months, not reached).

Data on other RET fusion-positive solid tumors In a patient population with a median follow-up time of 12.
1 months who have received adequate treatment, pratinib has shown clinical activity in a variety of other RET-driven tumor types.

Among the 19 patients with various RET fusion-positive solid tumors other than non-small cell lung cancer and thyroid cancer, the ORR was 53% (95% CI: 29%, 76%), and the median DOR was 19.
0 months (95% CI: 29%, 76%).
%CI: 5.
5 months, not assessable).

Patients with the following cancers (pancreatic cancer, cholangiocarcinoma, colon cancer, lung cancer (except NSCLC), mesenchymal cancer, salivary duct cancer, sweat gland cancer and thymic cancer) and tumors of patients diagnosed with primary cancer The lesions are reduced.

Of the three patients with pancreatic cancer, a type of tumor that is particularly difficult to treat, one achieved complete remission and the other two achieved partial remission.

Safety data as of November 6, 2020, the data cut-off date, a total of 471 patients received the recommended dose of pratinib 400 mg once a day.

Pratinib is well tolerated in patients with various tumors, and no new safety signals have been observed.

The most common treatment-related adverse events (AEs) (≥20%) reported by researchers were neutropenia, elevated aspartate aminotransferase (AST), anemia, decreased white blood cell count, elevated alanine aminotransferase (ALT), and hypertension , Constipation and weakness.

Overall, 6% of patients discontinued pratinib due to treatment-related adverse events.

These latest data will be presented in two posters at the ASCO annual meeting, one on RET fusion-positive NSCLC (abstract number: 9089), and the other on RET fusion solid tumors (abstract number: 3079).