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AK104 plus chemotherapy promising first-line option for gastric cancer

Presented by
Dr Jiafu Ji, Beijing Cancer Hospital, China
ASCO GI 2022
Phase 1/2, AK104-201
The combination therapy of the PD-1/CTLA-4 bispecific antibody AK104 plus chemotherapy showed promising activity and a manageable safety profile in patients with advanced gastric or gastroesophageal junction (GEJ) cancer [1]. The results of the current AK104-201 phase 1b/2 study drove the design of a phase 3 study investigating this combination therapy.

“Synergy between immune checkpoint inhibitors and chemotherapy in gastric or GEJ cancer has been demonstrated in 2 studies,” Dr Jiafu Ji (Beijing Cancer Hospital, China) said [2,3]. “In addition, we have learned that anti-PD-1 plus anti-CTLA-4 co-therapy outperforms anti-PD-1 alone, but at the cost of higher toxicity.”

The current phase 1b/2 AK104-201 study (NCT04380805) assessed the efficacy and safety of AK104, a PD-1/CTLA-4 bispecific antibody, in combination with XELOX or modified XELOX as first-line therapy for patients with gastric or GEJ cancer (n=96; mean age 62.7 years). Participants received doses of AK104 ranging between 4–15 mg/kg every 2 weeks. Objective response rate (ORR) based on RECIST v1.1 was the primary endpoint.

ORR was 65.9%, with 2.3% of the patients showing a complete response and 63.6% of the patients displaying a partial response. The ORR was numerically highest in the 10 mg/kg subgroup (83.3%) and lowest in the 6 mg/kg subgroup (56.4%). The median duration of response was 6.9 months. In the total cohort, the median progression-free survival was 7.1 months, and the median overall survival was 17.4 months.

The safety analysis did not reveal new safety issues of this combination. Moreover, no increase in treatment-related adverse events (TRAEs) was observed with dose escalation. Grade 3 or higher TRAEs were reported in 62.5% of the patients and the most common any-grade TRAEs were decreased platelet counts (28.1%), anaemia (26.0%), increased aspartate aminotransferase (26.0%), and decreased neutrophil count (22.9%).

Dr Ji concluded that the efficacy and safety data of this first-line treatment for patients with gastric or GEJ cancer are encouraging and need to be validated in the ongoing phase 3 study.

  1. Ji J, et al. AK104-201: A phase 1b/2, 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. Abstract 308, ASCO GI 2022, 20–22 January.

  2. Yelena YJ, et al. Lancet. 2021;398:27–40.

  3. Jianming X, et al. LBA53, ESMO 2021, 16–21 September.


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