-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Adenocarcinoma of the stomach or gastroesophageal junction (G/GEJ) is a common malignant tumor with a poor prognosis.
It ranks fifth among the most common malignancies and third among the causes of cancer deaths.
Capecitabine combined with oxaliplatin (CAPOX) is one of the standard first-line treatments for unresectable, locally advanced or metastatic G/GEJ adenocarcinoma.
In a phase 1 study, the PD-1 inhibitor carrelizumab showed anti-tumor activity against locally advanced or metastatic G/GEJ adenocarcinoma.
Previous studies have found that PD-1 inhibitors + VEGFR2 inhibitors can synergistically change the tumor microenvironment.
This combined treatment plan has attracted widespread attention.
Recently, the team of Professor Lin Shen from Peking University Cancer Hospital published the results of cohort 1 analysis in a multi-center, open-label, phase 2 clinical trial.
The trial evaluated carrelizumab combined with CAPOX, followed by carrelizumab.
The efficacy and safety of Rizumab+Apatinib as a first-line combination regimen for locally advanced or metastatic G/GEJ adenocarcinoma.
Research methodology This research involved two parallel cohorts.
Patients with human epidermal growth factor receptor 2 (HER2) negative, locally advanced or metastatic G/GEJ adenocarcinoma who have not received systemic treatment in the past were randomly assigned to cohort 1 or cohort 2 at 1:1.
Patients in cohort 1 received carrelizumab (200 mg) + CAPOX (capecitabine, 1000 mg/m2; oxaliplatin, 130 mg/m2) for 4-6 cycles without disease progression (PD) patients were treated with carrelizumab (200 mg) + apatinib (375 mg).
Patients in cohort 2 were treated with carrelizumab (200 mg) + apatinib (500 mg).
The primary endpoint of the study is the objective response rate (ORR), and the secondary endpoints include progression-free survival (PFS), duration of remission (DoR), disease control rate (DCR), and safety.
Research results The results of the analysis of cohort 1 are announced this time.
In cohort 1, all 48 patients were included in the efficacy and safety analysis population.
During the entire study period, the median treatment duration of carrelizumab was 21.
4 weeks (interquartile range [IQR], 13.
3-29.
4).
The median treatment duration of oxaliplatin and capecitabine were 14.
6 weeks (IQR, 9.
7-15.
7) and 17.
0 weeks (IQR, 13.
3-17.
6), respectively.
In the sequential treatment phase, the median treatment duration of carrelizumab and apatinib were 8.
9 weeks (IQR, 3.
4-24.
4) and 12.
1 weeks (IQR, 6.
4-28.
6), respectively.
After the study treatment ended, 31 patients (64.
6%) received at least one follow-up anti-tumor treatment.
Among these 48 patients, 1 case (2.
1%) achieved complete remission (CR), 27 cases (56.
3%) achieved partial remission (PR), 17 cases (35.
4%) had stable disease (SD), and the ORR was 58.
3% ( 28/48; 95% CI, 43.
2-72.
4).
Overall, 43 patients (89.
6%) had smaller target lesions compared with baseline.
The median DoR was 5.
7 months (95% CI, 4.
4-8.
3).
During the study period, 22 (78.
6%) of the patients who achieved CR/PR received karelizumab + CAPOX treatment and then received karelizumab + apatinib again.
In these patients, the DoR time is longer, with a median value of 7.
2 months (95% CI, 4.
4-10.
3).
As of the data cutoff date, the median PFS was 6.
8 months (95% CI, 5.
6-9.
5), and the median OS was 14.
9 months (95% CI, 13.
0-18.
6). Twenty-eight patients (58.
3%) showed tumor PD-L1 expression, of which 15 had PD-L1 CPS>1 and 13 had PD-L1 CPS≤1.
The ORR of the PD-L1 CPS>1 group was 53.
3% (95% CI, 26.
6-78.
7), and the PD-L1 CPS ≤1 group was 61.
5% (95% CI, 31.
6-86.
1).
The median PFS of patients with PD-L1 CPS>1 and PD-L1 CPS≤1 were 7.
1 months (95% CI, 5.
7-13.
1) and 5.
7 months (95% CI, 4.
0-not reached [NR]), respectively.
The median OS of the PD-L1 CPS>1 group was 15.
7 months (95% CI, 11.
7-not reached [NR]), and the median OS of the PD-L1 CPS ≤1 group was 14.
9 months (95% CI, 8.
4 -NR).
In terms of safety, the most common (>10%) level 3 treatment-related adverse events were decreased platelet count (20.
8%), decreased neutrophil count (18.
8%), and hypertension (14.
6%).
One patient (2.
1%) had treatment-related death due to abnormal liver function and interstitial lung disease.
Conclusion The researchers believe that for patients with locally advanced or metastatic G/GEJ adenocarcinoma, karelizumab combined with CAPOX, sequential karelizumab + apatinib as the first-line treatment program shows good anti-tumor Liveness and controllable safety.
This treatment option deserves further evaluation in a phase 3 randomized trial.
References: Peng Z, Wei J, Wang F, et al.
Camrelizumab combined with chemotherapy followed by camrelizumab plus apatinib as first-line therapy for advanced gastric or gastroesophageal junction adenocarcinoma.
Clin Cancer Res.
2021 Mar 25: clincanres.
4691.
2020.
doi : 10.
1158/1078-0432.
CCR-20-4691.
It ranks fifth among the most common malignancies and third among the causes of cancer deaths.
Capecitabine combined with oxaliplatin (CAPOX) is one of the standard first-line treatments for unresectable, locally advanced or metastatic G/GEJ adenocarcinoma.
In a phase 1 study, the PD-1 inhibitor carrelizumab showed anti-tumor activity against locally advanced or metastatic G/GEJ adenocarcinoma.
Previous studies have found that PD-1 inhibitors + VEGFR2 inhibitors can synergistically change the tumor microenvironment.
This combined treatment plan has attracted widespread attention.
Recently, the team of Professor Lin Shen from Peking University Cancer Hospital published the results of cohort 1 analysis in a multi-center, open-label, phase 2 clinical trial.
The trial evaluated carrelizumab combined with CAPOX, followed by carrelizumab.
The efficacy and safety of Rizumab+Apatinib as a first-line combination regimen for locally advanced or metastatic G/GEJ adenocarcinoma.
Research methodology This research involved two parallel cohorts.
Patients with human epidermal growth factor receptor 2 (HER2) negative, locally advanced or metastatic G/GEJ adenocarcinoma who have not received systemic treatment in the past were randomly assigned to cohort 1 or cohort 2 at 1:1.
Patients in cohort 1 received carrelizumab (200 mg) + CAPOX (capecitabine, 1000 mg/m2; oxaliplatin, 130 mg/m2) for 4-6 cycles without disease progression (PD) patients were treated with carrelizumab (200 mg) + apatinib (375 mg).
Patients in cohort 2 were treated with carrelizumab (200 mg) + apatinib (500 mg).
The primary endpoint of the study is the objective response rate (ORR), and the secondary endpoints include progression-free survival (PFS), duration of remission (DoR), disease control rate (DCR), and safety.
Research results The results of the analysis of cohort 1 are announced this time.
In cohort 1, all 48 patients were included in the efficacy and safety analysis population.
During the entire study period, the median treatment duration of carrelizumab was 21.
4 weeks (interquartile range [IQR], 13.
3-29.
4).
The median treatment duration of oxaliplatin and capecitabine were 14.
6 weeks (IQR, 9.
7-15.
7) and 17.
0 weeks (IQR, 13.
3-17.
6), respectively.
In the sequential treatment phase, the median treatment duration of carrelizumab and apatinib were 8.
9 weeks (IQR, 3.
4-24.
4) and 12.
1 weeks (IQR, 6.
4-28.
6), respectively.
After the study treatment ended, 31 patients (64.
6%) received at least one follow-up anti-tumor treatment.
Among these 48 patients, 1 case (2.
1%) achieved complete remission (CR), 27 cases (56.
3%) achieved partial remission (PR), 17 cases (35.
4%) had stable disease (SD), and the ORR was 58.
3% ( 28/48; 95% CI, 43.
2-72.
4).
Overall, 43 patients (89.
6%) had smaller target lesions compared with baseline.
The median DoR was 5.
7 months (95% CI, 4.
4-8.
3).
During the study period, 22 (78.
6%) of the patients who achieved CR/PR received karelizumab + CAPOX treatment and then received karelizumab + apatinib again.
In these patients, the DoR time is longer, with a median value of 7.
2 months (95% CI, 4.
4-10.
3).
As of the data cutoff date, the median PFS was 6.
8 months (95% CI, 5.
6-9.
5), and the median OS was 14.
9 months (95% CI, 13.
0-18.
6). Twenty-eight patients (58.
3%) showed tumor PD-L1 expression, of which 15 had PD-L1 CPS>1 and 13 had PD-L1 CPS≤1.
The ORR of the PD-L1 CPS>1 group was 53.
3% (95% CI, 26.
6-78.
7), and the PD-L1 CPS ≤1 group was 61.
5% (95% CI, 31.
6-86.
1).
The median PFS of patients with PD-L1 CPS>1 and PD-L1 CPS≤1 were 7.
1 months (95% CI, 5.
7-13.
1) and 5.
7 months (95% CI, 4.
0-not reached [NR]), respectively.
The median OS of the PD-L1 CPS>1 group was 15.
7 months (95% CI, 11.
7-not reached [NR]), and the median OS of the PD-L1 CPS ≤1 group was 14.
9 months (95% CI, 8.
4 -NR).
In terms of safety, the most common (>10%) level 3 treatment-related adverse events were decreased platelet count (20.
8%), decreased neutrophil count (18.
8%), and hypertension (14.
6%).
One patient (2.
1%) had treatment-related death due to abnormal liver function and interstitial lung disease.
Conclusion The researchers believe that for patients with locally advanced or metastatic G/GEJ adenocarcinoma, karelizumab combined with CAPOX, sequential karelizumab + apatinib as the first-line treatment program shows good anti-tumor Liveness and controllable safety.
This treatment option deserves further evaluation in a phase 3 randomized trial.
References: Peng Z, Wei J, Wang F, et al.
Camrelizumab combined with chemotherapy followed by camrelizumab plus apatinib as first-line therapy for advanced gastric or gastroesophageal junction adenocarcinoma.
Clin Cancer Res.
2021 Mar 25: clincanres.
4691.
2020.
doi : 10.
1158/1078-0432.
CCR-20-4691.
