Teriplizumab has a new indication, osimertinib + bevacizumab failed to bring benefits to drug-resistant patients

*Only for medical professionals to read for reference, 1 minute a day, to give you professional "talking information" in the tumor circle! (If you need the original text of the literature, you can add the editor WeChat yxj_oncology to obtain it) Key points: Annals of Oncology: Osimertinib combined with bevacizumab failed to give epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) ) Treatment failure patients bring survival benefits NEJM: Hypoxia-inducible factor-2α (HIF-2α) inhibitor Belzutifan in the treatment of Von Hippel-Lindau (VHL) syndrome-associated renal cell carcinoma (RCC) has a gratifying effect.
New drug: PI3Kδ inhibitor won Approval of clinical! New drug: Teriplizumab has a new indication 01Annals of Oncology: Osimertinib combined with bevacizumab failed to bring survival benefits to patients with failed EGFR-TKI treatment, although the third-generation EGFR-TKI osimerti Nitraria is the standard first-line treatment for patients with advanced EGFR-sensitive mutations and T790M-mutated non-small cell lung cancer (NSCLC), but patients may eventually develop resistance
.

Relevant studies have shown that tumor angiogenesis pathways may be related to EGFR-TKI resistance
.

BOOSTER is an open-label randomized phase II trial that compares osimertinib (80mg qd) combined with bevacizumab (15mg/kg q3w) and osimertinib monotherapy in the advanced stage of EGFR-TKI treatment failure.
Efficacy and safety of patients with EGFR sensitive mutation (19del/L858R) combined with T790M mutation NSCLC
.

The primary endpoint of the study is the PFS assessed by the investigator
.

Secondary endpoints are overall survival (OS), objective response rate (ORR) and adverse events (AE)
.

A total of 155 patients were enrolled in the study, 78 patients were assigned to the osimertinib combined with bevacizumab group, and 77 patients were assigned to the osimertinib single-agent group
.

After a median follow-up of 33.
8 months (IQR: 26.
5-37.
6), the results showed that the median PFS of patients in the osimertinib combined with bevacizumab group was 15.
4 months (95%CI 9.
2-18.
0).
The median OS was 24.
0 (95%CI 17.
8-32.
1) months and the ORR was 55%; the median PFS in the osimertinib monotherapy group was 12.
3 months (95%CI 6.
2-17.
2), and the median OS was 24.
3 Month (95%CI 16.
9-37.
0), ORR is 55%
.

The incidence rates of treatment-related adverse reactions above grade 3 in the two groups were 47% and 18%
.

At the same time, studies have shown that smoking history is significantly related to the PFS of patients.
The HR of smokers is 0.
52 (95% CI 0.
30-0.
90); the HR of non-smokers is 1.
47 (95% CI 0.
92-2.
33)
.

Studies have shown that osimertinib combined with bevacizumab for second-line treatment of patients with advanced EGFR-sensitive mutations and T790M mutations in NSCLC patients did not bring further survival benefits to patients
.

02NEJM: HIF-2α inhibitor Belzutifan has a gratifying effect in the treatment of VHL syndrome-related RCC.
VHL syndrome is a rare genetic disease.
One in 36,000 people suffers from the disease.
At the same time, nearly 70% of VHL patients will develop RCC
.

An open-label, single-arm Phase II study published in the New England Journal of Medicine explored the efficacy and safety of the HIF-2α inhibitor Belzutifan in the treatment of RCC related to VHL syndrome
.

The primary endpoint of the study is the objective response rate [ORR, complete response (CR) or partial response (PR)] assessed by the independent Central Radiology Review Board through RECIST1.
1
.

The results of the study showed that after treatment, of the 61 patients with VHL syndrome-related RCC included in the study, 30 (49%, 95% CI 36%-62%) achieved partial remission, and another 30 patients (49%) ) The disease is stable with an ORR of 49%
.

The 2-year PFS rate of patients was 95%
.

The most common AEs were anemia (90%) and fatigue (66%).
7 patients discontinued the drug, 4 of them voluntarily discontinued the drug, 1 patient discontinued the drug due to treatment-related AEs (dizziness: level 1), and 1 patient The patient discontinued the drug due to disease progression, and one patient died (acute toxic effects of fentanyl)
.

Studies have shown that Belzutifan has shown anti-tumor activity in the treatment of VHL syndrome-related RCC, and treatment-related adverse reactions can be controlled
.

03New drug: PI3Kδ inhibitor approved for clinical use! According to the latest announcement by the Center for Drug Evaluation (CDE) of the State Drug Administration of China, BeiGene's application for fumaric acid BGB-10188 capsules has obtained implied approval for two clinical trials.
BGB-10188 is a PI3Kδ inhibitor independently developed by BeiGene It is intended to be developed for the treatment of advanced malignant tumors
.

Phosphatidylinositol 3-kinase (PI3K) is a key regulatory kinase in the PI3K/AKT/mTOR signaling pathway
.

The PI3K signaling pathway plays an important role in regulating cell growth, metabolism and angiogenesis
.

At the same time, PI3K signaling pathway dysregulation exists in a variety of cancers.
The overactive PI3K signaling pathway is significantly related to tumor progression, increase in tumor microvessel density, and enhanced chemotaxis and invasiveness of cancer cells
.

04 New drug: Teriplizumab has another new indication.
On November 26, according to the latest announcement on the official website of the National Medical Products Administration (NMPA) of China, Junshi Bio-developed PD-1 inhibitor Teriplizumab ( Tuoyi) The listing application for the new indication has been approved
.

The new indications approved this time are: Tereprizumab combined with chemotherapy for advanced first-line recurrent and metastatic nasopharyngeal carcinoma (NPC) that has not received systemic treatment
.

The new indication approved this time is mainly based on the study of JUPITER-02
.

The study is a randomized, double-blind, placebo-controlled, international multi-center phase 3 clinical study led by Professor Xu Ruihua from the Cancer Hospital of Sun Yat-sen University.
) Efficacy and safety of first-line treatment of recurrent/metastatic nasopharyngeal carcinoma
.

The results showed that the PFS of the patients in the teriprizumab combined with chemotherapy group was significantly improved, the OS benefit trend has been observed, and the patient's risk of death was reduced by 40%, and it has good safety
.

References: [1] A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial https: // for Renal Cell Carcinoma in von Hippel–Lindau Disease https:// /NEJMoa2103425?query=featured_hematology-oncology[3]https://mp.
weixin.
qq.
com/s/VfM78Ccc85ytEJrbP4wTnA[4]https://mp.
weixin.
qq.
com/s/4wwGKHjdIwLhH3qPfDVSRQ