CheckMate-067 research data update, O+Y program enables patients with advanced melanoma to obtain 6-year OS!

*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 it to the editor's WeChat yxj_oncology to get it) Key points The Lancet Oncology: dabrafenib combined with trametinib may improve the current status of glioma treatment JCO: nivolumab combined with ipilimumab A new drug for the treatment of advanced melanoma with a median overall survival (OS) of up to 6 years: Envolizumab was approved for marketing! New drug: PD-L1/CTLA4 double antibody + chemotherapy for the treatment of advanced pancreatic cancer was approved Phase III clinical new drug: Vometinib is planned to be included in breakthrough therapy 01 The Lancet Oncology: Dabrafenib combined with trametinib may improve glioma Current status of treatment At present, there is still an urgent need for treatments that can improve the prognosis of patients with low- or high-grade gliomas
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A research report published in The Lancet Oncology evaluated the activity and safety of dabrafenib combined with trametinib in the treatment of BRAF V600E mutation-positive low- or high-grade gliomas
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This report is part of the ROAR basket trial, which included BRAF V600E mutation-positive low- or high-grade glioma patients over 18 years of age with an ECOG score of 0-2.
Among them, 45 patients with high-grade glioma (31 patients were Glioblastoma patients), 13 low-grade glioma patients
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The patient received dabrafenib (150 mg bid) combined with trametinib (2 mg qd) until the patient became intolerant, disease progressed or died
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The primary endpoint of the study is the objective response rate [ORR, high-grade glioma cohort: complete response (CR) + partial response (PR), low-grade glioma cohort: CR+PR+ mild Mitigation (minor response, MR)]
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The results of the study showed that in the high-grade glioma cohort, after a median follow-up of 12.
7 months (IQR 5.
4-32.
3), 15 out of 45 patients (33%; 95% CI 20%-49%) According to the investigator's assessment, there was objective remission.
Among them, 3 patients achieved CR and 12 patients achieved PR
.

In the low-grade glioma cohort, after a median follow-up of 32.
2 months (IQR 25.
1–47.
8), 9 out of 13 patients (69%; 95% CI 39%–91%) passed the investigator’s assessment.
Objective remission, including 1 CR patient, 6 PR patients and 2 MR patients
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A total of 31 patients had adverse reactions above grade 3.
The most common ones were fatigue [5 (9%)], decreased neutrophil count [5 (9%)], headache [3 (5%)] and neutrophils Cytopenia [3 (5%)]
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Studies have shown that dabrafenib combined with trametinib has shown clinically significant activity in the treatment of BRAF V600E mutation-positive low- or high-grade gliomas, and its safety performance is consistent with patients with other tumor types
.

02JCO: Nivolumab combined with ipilimumab in the treatment of advanced melanoma with median OS for up to 6 years.
Recently, the latest long-term follow-up data of the CheckMate-067 study was published in the internationally renowned oncology journal Journal of Clinical Oncology
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The previous research data of the CheckMate-067 study has demonstrated the long-term clinical benefit of nivolumab monotherapy or combined with ipilimumab in the first-line treatment of unresectable stage III/IV melanoma.
This data update reported 6.
5 years (the shortest Follow-up time) Efficacy and safety data after follow-up
.

The study included 945 patients with unresectable stage III/IV melanoma who were randomly divided into the nivoliumab combined with ipilimumab group (n=314) and nivoliumab at a ratio of 1:1:1.
Drug group (n=316) and ipilimumab single-drug group (n=315)
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Patients in the nivolumumab combined with ipilimumab group received nivolumumab (1 mg/kg q3w) combined with ipilimumab (3 mg/kg q3w) after 4 cycles of treatment Anti-(3 mg/kg q2w) maintenance therapy, patients in the nivolumab monotherapy group received nivolumab (3 mg/kg q2w) combined with placebo treatment, and patients in the ipilimumab monotherapy group received ipilimumab Lumumab (3 mg/kg q3w) combined with placebo was treated for 4 cycles
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The primary endpoints of the study included progression-free survival (PFS) and OS of the three groups of patients, and the secondary endpoints included nivolumumab combined with ipilimumab and nivolumumab as a single-agent treatment efficacy, safety assessment, and melanin Tumor-specific survival (MSS)
.

The latest data show that the median OS of patients in the nivolumab combined with ipilimumab group was 72.
1 months, and the median MSS was not reached; the median OS of patients in the nivolumab monotherapy group was 36.
9 months, with a median The MSS was 58.
7 months; the median OS of patients in the ipilimumab monotherapy group was 19.
9 months, and the median MSS was 21.
9 months
.

Among the three groups of patients, the 6.
5-year OS rates of BRAF mutant patients were 57%, 43%, and 25%, respectively, and the 6.
5-year OS rates of BRAF wild-type patients were 46%, 42%, and 22%, respectively
.

The updated data of the CheckMate-067 study is the longest report of median OS and MSS in the phase III melanoma study so far, indicating that the use of nivolumab combined with ipilimumab in the treatment of patients with advanced melanoma can last forever Improve patient symptoms
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03New drug: Envolizumab was approved for marketing! On November 25, 2021, the National Medical Products Administration (NMPA) of China approved the PD-L1 inhibitor Envolimab for the listing of unresectable or metastatic highly unstable microsatellites (MSI) through the priority review and approval process.
-H) or the treatment of adult patients with advanced solid tumors with mismatch repair gene defects (dMMR), including patients with advanced colorectal cancer who have progressed after treatment with fluorouracil, oxaliplatin, and irinotecan and previous treatments Later, patients with advanced solid tumors who developed disease progression and did not have satisfactory alternative treatment options
.

04New drug: PD-L1/CTLA4 double antibody + chemotherapy for the treatment of advanced pancreatic cancer was approved for phase III clinical trials.
On November 24, Corning Jereh Biopharmaceuticals announced the PD-L1/CTLA-4 bispecific antibody KN046 developed by the company The Phase III registration clinical study (KN046-303) of the combination of albumin paclitaxel and gemcitabine in the treatment of advanced pancreatic cancer was approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration
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This study aims to compare the efficacy and safety of KN046 with placebo combined with albumin paclitaxel and gemcitabine in the treatment of patients with untreated, unresectable locally advanced or metastatic pancreatic cancer
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The primary endpoint of the study was the PFS and OS assessed by the Independent Review Committee (IRC), and the key secondary endpoint was the ORR assessed by the IRC
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Previously, a phase II clinical study on KN046 combined with albumin paclitaxel and gemcitabine in the first-line treatment of advanced pancreatic ductal adenocarcinoma (PDAC) showed that compared with the AG regimen (albumin paclitaxel combined with gemcitabine), KN046 combined with albumin paclitaxel and gemcitabine It can more than double the patient's ORR
.

The research made its debut at the 2021 American Society of Clinical Oncology (ASCO) annual meeting in the form of a poster, and the updated data of this research was announced at this year's Chinese Society of Clinical Oncology (CSCO) conference
.

05 New drug: Vometinib is planned to be included in breakthrough therapy.
On November 23, the CDE official website showed that Allis Medical’s vormetinib mesylate tablets are planned to be included in breakthrough therapy.
The first-line treatment has epidermal growth factor receptor (EGFR) ) Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion or exon 21 (L858R) substitution mutation
.

Vometinib mesylate is a third-generation EGFR-tyrosine kinase inhibitor (TKI), which has the characteristics of "dual activity, high selection, strong tumor shrinkage, and good safety"
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In March 2021, it was approved for marketing by the National Medical Products Administration in China for the treatment of locally advanced or metastatic NSCLC adults who have experienced disease progression during or after treatment with EGFR-TKI and confirmed to have EGFR T790M mutation positive after testing.
Patient
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Some time ago, the Phase III clinical study of vomitinib for the first-line treatment of locally advanced or metastatic NSCLC with EGFR sensitive mutations-FURLONG study, reached the main research focus of PFS.
Compared with gefitinib, vometinib significantly improved the patient’s PFS benefits
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References: 1.
Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial https:// com/journals/lanonc/article/PIIS1470-2045(21)00578-7/fulltext2.
Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma https://ascopubs.
org/doi/abs/ 10.
1200/JCO.
21.
022293.
https:// 4.
https://mp.
weixin.
qq.
com/s/onIBq0Mc4wCjDTcNVPKJgA5.
https://mp.
weixin.
qq.
com/s/D8zJdFG-1GtB8q8-dZr1Vg