One is listed in JCO, the other is pancreatic cancer, these two KARS inhibitors are worth paying attention to tumor intelligence

*Only for medical professionals to read and reference for 1 minute a day, to give you professional "talks" in the tumor circle! (If you want the original text of the document, you can add Xiaobian WeChat yxj_oncology to get it) Key points J Clin Oncol: Another new KRASG12C inhibitor shows considerable efficacy in solid tumors BLOOD: New CAR-T product shows safety in primary CNS lymphoma New Drug: Novel KRASG12C Inhibitor Shows High Disease Control Rate in Advanced Pancreatic Cancer New Drug: Novel c-MET Inhibitor Approved in China Adagrasib (MRTX849) is an oral, highly selective, small molecule KRASG12C inhibitor
.

Recently, the results of a Phase I/IB study of adagrasib in patients with non-small cell lung cancer, colorectal cancer and other solid tumors harboring KRASG12C mutations were published in the Journal of Clincal Oncology for the first time
.

Studies have shown that Adgrasib (600mg twice daily) showed antitumor activity and was well tolerated in patients with advanced solid tumors harboring a KRASG12C mutation
.

Screenshot of the official website In this study, the researchers recruited a total of 25 patients with advanced KRASG12C-mutated solid tumors
.

Patients received oral Adagrasib 150 mg once daily, 300 mg once daily, 600 mg once daily, 1200 mg once daily, or 600 mg twice daily
.

The investigators assessed safety, pharmacokinetics, and clinical activity
.

RESULTS: Based on safety, tolerability and observed pharmacokinetics, the recommended phase II dose (RP2D) is 600 mg twice daily, and the maximum tolerated dose has not been formally defined
.

After a median follow-up of 19.
6 months, 8 of 15 patients with KRASG12C-mutated non-small cell lung cancer (53.
3%; 95% CI: 26.
6%-78.
7%) treated with Adagrasib 600 mg twice daily, based on RECIST assessment.
Confirmed partial response, median duration of response was 16.
4 months (95% CI: 3.
1 - not estimable), and median progression-free survival (PFS) was 11.
1 months (95% CI: 2.
6 - not estimable)
.

One of two patients with KRASG12C-mutant colorectal cancer achieved a partial response (response duration 4.
2 months) with Adagrasib 600 mg twice daily
.

In patients receiving RP2D, the most common treatment-related adverse events were nausea, diarrhea, vomiting, and fatigue
.

The most common grade 3-4 treatment-related adverse event was fatigue
.

02BLOOD: Novel CAR-T Product Demonstrates Safety and Efficacy in Primary CNS Lymphoma Patients with primary central nervous system lymphoma (PCNSL) are often Excluded from CAR-T studies
.

Recently, the results of a phase I/II clinical trial in a highly refractory PCNSL patient population were published in the journal BLOOD
.

Overall, Tisagenlecleucel, a CAR-T product targeting CD19, is safe and effective in PCNSL, a highly refractory patient population
.

In this study, 12 patients with relapsed PCNSL were treated with Tisagenlecleucel with a median follow-up of 12.
2 months
.

Grade 1 cytokine release syndrome (CRS) was observed in 7 patients (58.
3%), low-grade ICANS was observed in 5 patients (41.
6%), and grade 3 ICANS was observed in only 1 patient
.

Seven patients (58.
3%) experienced remission, including 6 patients (50%) who experienced complete remission (CR), and 3 patients sustained complete remission at the time of data cutoff
.

There were no treatment-related deaths
.

Tisagenlecleucel is multiplied in peripheral blood and transported into the central nervous system (CNS)
.

An exploratory analysis found that T cells, CAR-T cells and macrophages were found in the cerebrospinal fluid (CSF) of the patients after the infusion compared to baseline
.

03New Drug: Novel KRASG12C Inhibitor Shows High Disease Control Rate in Advanced Pancreatic Cancer Recently, Amgen announced the latest results of its KRASG12C inhibitor Sotorasib clinical study
.

Sotorasib demonstrated considerable activity and benefit/risk ratio in patients with KRASG12C-mutated advanced pancreatic cancer
.

Among 38 patients with advanced pancreatic cancer who had undergone multiple lines of therapy, the objective response rate with sotorasib was 21% and the disease control rate was 84%
.

At a median follow-up of 16.
8 months, the median duration of response was 5.
7 months, the median PFS was 4 months, and the median overall survival was nearly 7 months
.

04New drug: A new c-MET inhibitor is approved for clinical use in China Recently, the Center for Drug Evaluation (CDE) of the State Drug Administration of China recently announced that ASKC202, a small molecule inhibitor targeting c-MET, obtained by Osaikang Pharmaceuticals has obtained clinical trials Implied license, indication for advanced solid tumors
.

ASKC202 has previously demonstrated its activity in preclinical studies and is expected to provide a new treatment option for patients with c-MET mutations
.

Reference: 1.
Ou SI, et al.
First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1) [published online ahead of print, 2022 Feb 15].
J Clin Oncol.
2022; JCO2102752.
doi:10.
1200/JCO.
21.
02752https://ascopubs.
org/doi/full/10.
1200/JCO.
21.
027522.
Frigault MJ, et al.
Safety and Efficacy of Tisagenlecleucel in Primary CNS Lymphoma: A phase I/II clinical trial [published online ahead of print, 2022 Feb 15].
Blood.
2022;blood.
2021014738.
doi:10.
1182/blood.
2021014738 https://ashpublications.
org/blood/article-abstract/ doi/10.
1182/blood.
2021014738/484042/Safety-and-Efficacy-of-Tisagenlecleucel-in-Primary?redirectedFrom=fulltext3.
https://mp.
weixin.
qq.
com/s/l9Ynp1oXtsraTxRlqnSuRA4.
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https:// mp.
weixin.
qq.
com/s/Yawf959Lkk0YZWWf7GfVOg