NMPA Approval

March 21, 2022 Ensartinib (first-line treatment for lung cancer)

On March 21, 2022, Betta Pharmaceuticals Co., Ltd. received the "Drug Registration Certificate" issued by the State Drug Administration (drug approval number: GUO XIE ZHU ZHUN H20200009, GUO YAO ZHUN ZI H20200010), Ensartinib. hydrochloride capsule has been approved for marketing as a new indication for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) (referred to as "first-line treatment indication"), which is the second indication approved by Ensartinib. The above approval is based on the eXalt 3 multicenter clinical study. The eXalt 3 study is a global open multicenter randomized controlled phase III clinical study designed to evaluate the effect and safety treatment of Ensartinib versus Crizotinib on untreated (first-line) patients with ALK. positive in NSCLC patients. In the eXalt 3 global multi-center clinical study, the 4-year OS rate of Ensartinib in the baseline population without brain metastases reached 75.7%; the 4-year OS rate in the baseline population with brain metastases reached 47.7%; the 4-year OS rate in the overall population reached 66.3% %. ^[1]

March 24, 2022, Dabrafenib combined with Trametinib (full line treatment for lung cancer)

On March 25, 2022, the Novartis Group WeChat Page announced that Novartis (China) dual-targeted combination therapy drug Tafinlar^® Dabrafenib mesylate Capsules  and Mekinist^® indication for the treatment of BRAF V600 mutation-positive metastatic non-small cell lung cancer. The approval of the indications in China is based on the registered clinical study on the treatment of BRAF mutation-positive metastatic NSCLC in the Chinese population with Dabrafenib combined with Trametinib. This study is a national multicenter phase II clinical trial led by Professor Zhang Li from the Cancer Prevention and Treatment Center of Sun Sun Yat-sen University. The study confirmed that Dabrafenib combined with Trametinib has excellent efficacy in treating metastatic NSCLC with BRAF V600E mutation. ^[2]

March 24, 2022 Brigatinib (first line treatment lung cancer)

On March 24, 2022, the ALK inhibitor Brigatinib of Takeda Pharmaceutical was approved by NMPA for marketing, which is applicable to the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) positive. Alunbrig^® (Brigatinib) was approved based on the research data of the global phase clinical trial ALTA-1L. The results of the study confirmed that the acceptance of Alunbrig^® The median PFS of patients treated with (Brigatinib Tablets) reached 24 months after evaluation by the independent review committee, while the median PFS of the control group was 11.1 months (HR=0.48, P<0.0001), and the median PFS of the researchers reached 30.8 months compared with 9.2 months in the control group (HR=0.43, P<0.0001), which reduced the risk of disease progression or death by 57% compared with the control group. In addition, it has a breakthrough effect on patients with baseline brain metastasis: the median PFS reached 24 months after evaluation by the independent review committee, and 5.6 months in the control group (HR=0.25, P<0.0001), significantly reducing the risk of disease progression or death by 75% compared with the control group. Alunbrig^®The 4-year OS rate of patients with brain metastasis at the baseline of first-line treatment was 71%, and the risk of death was reduced by 57% (the 4-year OS rate of the control group was 44%, HR=0.43, P=0.02). ^[3]

April 8, 2022 Larotrectinib (NTRK solid tumor)

On April 8, 2022, the National Drug Administration (NMPA) approved the tumor precise treatment drug, Larotrectinib Vitrakvi^®） It is used for the treatment of adult and child solid tumor patients with NTRK gene fusion. Larotrectinib is the world's first accurate targeted drug with unlimited tumor types, with indications covering all ages (including infants), and is the first choice for patients with advanced NTRK gene fusion tumor ^[4]. Clinical research shows that ^[5], the objective response rate of lung cancer is 75%, and that of thyroid cancer, fibrosarcoma and gastrointestinal stromal tumor is as high as 100%! According to the summary data of three large clinical trials of patients with NTRK gene fusion positive tumors, the total remission rate of Larotrectinib is 75%, and 22% of patients have complete remission.

April 29, 2022 Larotrectinib (first-line/second-line for lung cancer)

On April 29, 2022, the third-generation ALK inhibitor Lorlatinib was approved by NMPA as a single agent for anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) patient. The latest data from the CROWN study showed that the three-year progression-free survival rate of Lorlatinib in the first-line treatment of ALK-positive non-small cell lung cancer was as high as 63.5% when the treatment follow-up was up to 36.7 months. Based on the available data, the researchers extrapolated that the progression-free survival of Lorlatinib in the first-line treatment of ALK-positive NSCLC would exceed 60 months ^[6].

June 30, 2022 Furmonertinib (first-line for lung cancer)

On June 30, 2022, China's National Medical Products Administration (NMPA) announced on its official website that Furmonertinib Mesilate Tablets  was approved as a single-drug first-line treatment for patients with epidermal growth factor receptor (EGFR) receptors. Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion (19DEL) or exon 21 (L858R) substitution mutation. The approval of the above indications is based on the results of a national multi-center, randomized controlled, double-blind phase III registration clinical study (FURLONG). In March 2022, the European Conference on Lung Cancer announced the results of the FURLONG study. On June 2, 2022, the full text of the FURLONG study was published in the top journal "The Lancet Journal of Respiratory Medicine" ^[7].

July 13, 2022 Trilaciclib (before chemotherapy)

On July 13, 2022, according to the official website of the National Medical Products Administration (NMPA), Simcere Pharmaceutical Group Limited and G1 Therapeutics jointly developed the world's first innovative drug  Trilaciclib ( Triraciclib Hydrochloride for Injection) was conditionally approved for marketing in China with the approval number HJ20220066. The approved indication of Trilaciclib is "applicable to patients with extensive-stage small cell lung cancer (ES-SCLC) who have not received systemic chemotherapy in the past. Can reduce the incidence of chemotherapy-induced myelosuppression".

National Medical Products Administration announced the approval of Trilaciclib

July 29, 2022 Entrectinib (full line for lung cancer)

On July 29, 2022, China's National Medical Products Administration (NMPA) announced on its official website that Roche's Entrectinib (Rozlytrek) has been approved for marketing in China! Entrectinib is an NTRK/ROS1 dual-target inhibitor, and the approved indication this time is NTRK fusion-positive locally advanced and metastatic solid tumors. This is the second NTRK inhibitor approved for marketing in China after Larotrectinib (Vitrakvi^®). The approval is mainly based on the combined analysis results of 3 Phase I/II clinical studies (ALKA-372-001, STARTRK-1 and STARTRK-2 trials). The efficacy evaluation population included 168 patients who had not previously received ROS1 inhibitor therapy. Based on the data update of the 2022 World Conference on Lung Cancer (WCLC), in the first-line treatment of ROS1-positive NSCLC patients, the overall objective response rate (ORR) of entrectinib reached 68.7%, and the median duration of response (DOR) reached 35.6 months , the median progression-free survival (PFS) was 17.7 months, and the median overall survival (OS) was 47.7 months.

The risk of intracranial metastasis in patients treated with Entrectinib for 12 months was only 1%; in 25 patients with baseline measurable CNS metastasis, the intracranial ORR was 80%, showing intracranial anti-tumor effect, and the drug is safe Tolerable ^{[8, 9, 10]}.

October 8, 2022 Savolitinib (full line for lung cancer)

On October 8, 2022, Eli Lilly and Company announced that the highly selective RET inhibitor Selpercatinib (40mg & 80mg capsules) has been approved by the National Medical Products Administration (NMPA) for the treatment of RET rearrangement adult patients with fusion-positive locally advanced or metastatic non-small cell lung cancer (NSCLC), adult patients with advanced or metastatic RET-mutant medullary thyroid carcinoma (MTC) requiring systemic therapy, and pediatric patients aged 12 and over, and those requiring systemic therapy treatment of adult and pediatric patients 12 years and older with advanced or metastatic RET fusion-positive thyroid cancer (TC) that is refractory to radioactive iodine (if radioactive iodine is indicated). The approval is based on data from two global studies, LIBRETTO-001 and LIBRETTO-321, for the use of Selpercatinib in the Chinese population.

From: Insight Database

FDA- Approval

December 12, 2022 Adagrasib (second-line for lung cancer)

On December 12, 2022, the U.S. Food and Drug Administration (FDA) approved the RAS GTPase family inhibitor Adagrasib (Krazati, Mirati Therapeutics, Inc.) for locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation adult patients who have received at least one prior systemic therapy, as determined by an FDA-approved test. The above approval is based on the conclusions of the NCT03785249 clinical trial, which includes locally advanced or metastatic NSCLC patients with KRAS G12C mutation. Efficacy was evaluated in 112 patients whose disease progressed on or after platinum-based chemotherapy and immune checkpoint inhibitors (administered simultaneously or sequentially). Patients received Adagracib 600 mg orally twice daily until disease progression or unacceptable toxicity. The primary efficacy outcome measures were objective response rate (ORR) according to RECIST 1.1, as assessed by blinded independent central review, and duration of response (DOR). The ORR was 43% (95% CI: 34%, 53%), and the median DOR was 8.5 months (95% CI: 6.2, 13.8).

Link：FDA grants accelerated approval to adagrasib for KRAS G12C-mutated NSCLC | FDA

Reference

[1] JAMA Oncol. 2021 Nov 1;7(11):1617-1625. doi: 10.1001/jamaoncol.2021.3523.

[2] Lancet Oncol. 2017 Oct;18(10):1307-1316. doi: 10.1016/S1470-2045(17)30679-4. Epub 2017 Sep 11.

[3] J Clin Oncol. 2020 Nov 1;38(31):3592-3603. doi: 10.1200/JCO.20.00505. Epub 2020 Aug 11.

[4] On April 13, 2022, the information on drug approval certificates to be collected will be released (nmpa.gov.cn)

[5]A Drilon,et al.2022 ASCO Abstract 3100.

[6]AACR Annual Meeting 2022 Itinerary Planner | Presentation (abstractsonline.com)

[7] Lancet Respir Med. 2022 Nov;10(11):1019-1028. 

[8] https://clinicaltrials.gov/ct2/show/NCT02568267.

[9] https://clinicaltrials.gov/ct2/show/NCT02097810

[10] F. Hoffman La Roche Ltd. Data on file.