2022 ASCO GI AK104 combined with chemotherapy may become a new first-line treatment option for patients with advanced G/GEJ adenocarcinoma

The 2022 American Society of Clinical Oncology Symposium on Gastrointestinal Oncology (ASCO GI) was held from January 20 to 22 local time, and a number of blockbuster studies have been announced
.

During the meeting, Professor Ji Jiafu from Peking University Cancer Hospital reported that the research group led by him evaluated the efficacy and safety of bispecific antibody AK104 combined with chemotherapy in gastric (G) or gastroesophageal junction (GEJ) cancer.
The results suggest that this strategy may become a new first-line treatment option for patients
.

Below are the details of the study
.

Background: Anti-PD-1 agents combined with chemotherapy as first-line treatment for advanced G/GEJ cancer have achieved overall survival (OS) and progression-free survival (PFS) benefits compared with chemotherapy alone (Checkmate-649), suggesting that immunological examination There is synergistic activity between point inhibitors and chemotherapy
.

Consistently, the combination of anti-PD-1 and anti-CTLA-4 has shown higher response rates but also greater toxicity than PD-1 monotherapy
.

We conducted this phase Ib/II study to evaluate the efficacy of AK104 (a PD-1/CTLA-4 bispecific antibody) in combination with XELOX (capecitabine and oxaliplatin) or modified XELOX (mXELOX) in Efficacy and safety in first-line treatment of G/GEJ cancer
.

This study is registered with ClinicalTrials.
gov (NCT03852251)
.

Methods Patients with unresectable advanced G/GEJ adenocarcinoma who had not received prior systemic therapy were enrolled, regardless of PD-L1 status, and known HER2-positive patients were excluded
.

The enrolled patients received AK104 (4 mg/kg, 6 mg/kg, 10 mg/kg Q2W or 10 mg/kg, 15 mg/kg Q3W) + chemotherapy (mXELOX Q2W or XELOX Q3W)
.

The primary endpoint was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.
1 (RECIST v1.
1)
.

Results As of August 13, 2021, 96 patients were enrolled, with a median age of 62.
7 years (range, 29-75), 70.
8% were male, 62.
5% had an ECOG PS of 1, and 44.
8% had liver metastases
.

The median follow-up time was 9.
95 months (range, 0.
4-26.
8)
.

Eighty-eight patients (92%) had at least one post-baseline tumor assessment
.

The ORR was 65.
9% (58/88), with 2 (2.
3%) complete responses and 56 (63.
6%) partial responses
.

The disease control rate (DCR) was 92.
0% (81/88)
.

The median duration of response (DoR) was 6.
93 months (95% CI, 4.
60-11.
20)
.

The median PFS was 7.
10 months (95% CI, 5.
55-10.
48)
.

The median OS was 17.
41 months (95% CI, 12.
35-NE)
.

Among patients with PD-L1 CPS ≥ 1 and CPS < 1, the median OS was 17.
41 months and 14.
65 months, respectively
.

The incidence of treatment-related adverse events (TRAEs) was 97.
9%, the most common being decreased platelet count (60.
4%), decreased white blood cell count (58.
3%), decreased neutrophil count (56.
3%), anemia (47.
9%), Nausea (30.
2%), vomiting (30.
2%), increased aspartate aminotransferase (30.
2%)
.

The incidence of grade 3 and above TRAEs was 62.
5%
.

No new safety signals were found
.

Conclusions AK104 combined with mXELOX/XELOX shows promising activity and manageable safety in previously untreated patients with advanced G/GEJ adenocarcinoma
.

AK104 in combination with chemotherapy represents a potential new option for first-line treatment for these patients
.

A phase III study of AK104 in combination with chemotherapy as first-line treatment for G/GEJ cancer is ongoing
.

References: A phase Ib/II, multicenter, open-label study of AK104, a PD-1/CTLA-4 bispecific antibody, combined with chemotherapy (chemo) as first-line therapy for advanced gastric (G) or gastroesophageal junction ( GEJ) cancer.