O drug is approved as the first-line gastric cancer, what other domestic immune combination therapies are worth looking forward to?

Recently (April 16) a major event in the tumor circle is the FDA approval of BMS (Bristol-Myers Squibb)'s PD-1 monoclonal antibody nivolumab (opdivo, referred to as O drug) combined with chemotherapy for the first-line treatment of advanced or metastatic disease Patients with gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma
.

This is the first first-line immunotherapy approved by the FDA for the treatment of gastric cancer

This approval is based on a study code-named CheckMate-649, which is a randomized, multicenter, open phase III clinical study designed to evaluate the use of nivolumab combined with chemotherapy in comparison with chemotherapy alone Efficacy in the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma
.

The patients included in the study have not received treatment in the past, and the expression of HER2 is negative

The primary endpoint of the study is the overall survival (OS) of patients with PD-L1 positive expression (CPS≥5) compared with chemotherapy alone, nivouximab (drug O) combined with chemotherapy, and based on a blinded independent center review Progression-free survival (PFS) assessed by the Committee (BICR)
.

A total of 2032 samples were included in the entire study, and there were a total of 208 patients in the Chinese subgroup
.

The results of the study showed that in terms of OS, in patients with PD-L1 CPS≥5, the median OS of the combined treatment group was 15.

Compared with chemotherapy, the combination therapy group showed a clinically significant overall survival benefit

(A) PD-L1 CPS≥5; (b) PD-L1 CPS≥1; (c) all groups

In terms of progression-free survival (PFS), among patients with PD-L1 CPS ≥ 5, the median PFS of the combined treatment group was 8.
5 months, and that of the chemotherapy group alone was 4.
3 months (Figure a)
.

Among patients with PD-L1 CPS≥1, the median PFS of the combined treatment group was 8.

       Compared with chemotherapy, the combination treatment group showed a clinically significant progression-free survival benefit

       (A) PD-L1 CPS≥5; (b) PD-L1 CPS≥1; (c) all groups

       In the Chinese population, compared with chemotherapy alone, nivolumab combined with chemotherapy has achieved clinically significant OS and PFS benefits in the first-line treatment of unresectable advanced or metastatic gastric cancer and gastroesophageal junction cancer
.

Regardless of whether PD-L1 expression is positive and the combined positive score (CPS) ≥ 5, CPS ≥ 1, or all random populations, OS and PFS benefits have been observed

       In addition to imported PD-1 monoclonal antibody O drugs showing good efficacy in gastric cancer, domestic PD-1 monoclonal antibodies are also catching up.
Let's take a look at what combinations are worth looking forward to
.

       1.
Carrelizumab combined with capecitabine + oxaliplatin (CAPOX) followed by carrelizumab combined with apatinib

       On March 25, the journal "Clinical Cancer Research" published an online publication of karelizumab combined with capecitabine + oxaliplatin (CAPOX) sequential karelizumab combined with apati The results of the first-line treatment of the first-line treatment of HER2-negative advanced gastric/gastroesophageal junction adenocarcinoma with Nissin regimen
.

This national multi-center phase II clinical trial was led by Professor Lin Shen from Peking University Cancer Hospital.

       In the study of carrelizumab combined with CAPOX sequential carrelizumab combined with apatinib, the OS of the whole population has reached 14.
9 months, which once again proves the potential of combined immunotherapy
.

       2.
Sintilimab combined with chemotherapy as the first-line treatment of adenocarcinoma of the gastroesophageal junction

       The study is an open-label, multi-center, phase Ib study that included 20 patients with unresectable advanced or metastatic gastroesophageal junction adenocarcinoma
.

The patient received an intravenous injection of 200 mg Sintilizumab combined with CapeOx, administered every 21 days for 6 cycles; after the combined treatment, the patient continued to receive Sintilizumab (200 mg) as maintenance therapy, once every 3 weeks

       The results of the study show that ORR is 85%, both are PR; DCR is 100%
.

The median PFS was 7.

       3.
Teriplizumab combined with chemotherapy as the first-line treatment of advanced gastric cancer

       This is an open-label, multicenter, phase Ib/II trial in which patients with advanced gastric cancer are divided into 2 cohorts
.
In cohort 1, 58 patients with chemotherapy-refractory advanced gastric cancer received teriprizumab (3 mg/kg d1, Q2W) monotherapy
.
In cohort 2, 18 chemotherapy-naive patients with advanced gastric cancer received teriprizumab (360mg d1, Q3W) combined with XELOX regimen (oxaliplatin 130mg/m2qd, d1; capecitabine 1000mg/m2BID, d1-d14 ; Q3W) as a first-line treatment
.

       The results showed that in terms of efficacy, the ORR of patients in cohort 1 (refractory advanced gastric cancer) was 12.
1%, the DCR was 39.
7%, the median DOR was 9.
4 months, the median PFS was 1.
9 months, and the median OS was 4.
8 months.

.
The ORR of cohort 2 patients was 66.
7%, the DCR was 88.
9%, the median PFS was 5.
8 months, and the median OS was not reached
.

       4.
Tilelizumab combined with chemotherapy is under research

       Tilelizumab is a PD-1 humanized monoclonal antibody independently developed by BeiGene.
It was approved by the NMPA in December 2019 for use in relapsed/refractory classic Hodgkin’s lymphoma (r/r cHL).
)
.
In April 2020, tislelizumab became the first PD-1/PD-L1 monoclonal antibody approved for urothelial cancer indications in China
.

       In September 2020, the results of the RATIONALE-205 study of tislelizumab combined with chemotherapy for the first-line treatment of esophageal squamous cell carcinoma and gastric/gastroesophageal junction cancer were officially published in Clinical Cancer Research
.
A total of 15 patients were enrolled in the gastric/gastroesophageal junction cancer cohort of this study.
The ORR and DCR were 46.
7% and 80%, respectively.
The combination of tislelizumab and chemotherapy has a long-lasting effect, and the median DoR is not yet mature
.
In terms of safety, the most common adverse events (AE) include anemia, decreased appetite, nausea, and fatigue
.
On this basis, a global randomized, double-blind, multi-center Phase III study of tislelizumab combined with chemotherapy and placebo combined with chemotherapy for the first-line treatment of advanced gastroesophageal junction cancer is underway
.

       It can be seen from the above that the domestic PD-1 monoclonal antibody has also delivered a good answer in the field of gastric cancer and obtained breakthrough data.
It is expected that it will be launched as soon as possible to provide more choices for cancer patients
.

       Reference source:

       1.
https://       2.
Lin Shen et al.
First-line nivolumab plus chemotherapy versus chemotherapy in patients with advanced gastric cancer/gastroesophageal junction cancer/ esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis.
2021 AACR;

       3.
Camrelizumab combined with chemotherapy followed by camrelizumab plus apatinib as first-line therapy for advanced gastric or gastroesophageal junction adenocarcinoma.

       4.
Clin Cancer Res.
2020 Sep1;26(17):4542-4550.