Gastroesophageal adenocarcinoma (GEA) : ESMO 2021

ESMO 2021 has already begun, with major key players such as Roche, Daiichi Sankyo, Mirati Therapeutics, Merck, BMS, Innovent Biologics, Coherus BioSciences, Leap Therapeutics, BeiGene, MacroGenics, Zymeworks, Bayer, Taiho Oncology, and others set to present the updated findings from their lead candidates targeting various oncology indications including GI Cancer.

Delveinsight has already published post-conference insights on Marcrogenics' Margetuximab and Zymework's Zanidatamab in first-line HER2 expressing gastric cancers. Apart from Macrogenics and Zymework, Leap Therapeutics, in collaboration with BeiGene, also presented recent findings from its Phase II DisTinGuish Trial (NCT04363801) evaluating DKN-01 in combination with tislelizumab and chemotherapy as first-line therapy (LOT) in patients with advanced GEA. As per the company, the combination was well tolerated with encouraging early activity as the first LOT for advanced GEA (unselected for PD-L1), with significant clinical benefit among those patients with PD-L1-low expression, the ORR was 79%, with 100% in DKK1-high patients and 57% in DKK1-low patients. Among those patients with PD-L1-high expression, the ORR was 67%, with 75% ORR in DKK1-high patients and 50% in DKK1-low patients. Adverse events with grade ≥3 were reported in 52% of the patients. Additionally, median DoR and PFS data are not yet mature and are expected in the first half of 2022. Conclusively, results presented at the ESMO Congress showed robust objective clinical responses achieved from this

Expert views: "Initial data from this trial have shown that patients with high levels of DKK1 expression, a group with a poor prognosis, had encouraging responses to treatment. The additional data presented show evidence that not only is DKK1 a critical biomarker in predicting response to DKN-01 and tislelizumab therapy, but also that the combination can induce deep responses regardless of the patient's PD-L1 status, including particularly poor prognosis patients with both low PD-L1 and high DKK1. Taken together, these are promising results for the combination therapy of DKN-01 with tislelizumab and chemotherapy in first-line patients with gastric or gastroesophageal junction cancers."

Member of the Faculty at Massachusetts General Hospital Cancer Centre and Harvard Medical School

INSIGHTS: It is quite well known that DKK1 is significantly expressed in various cancers and could be a biomarker for targeted therapy and a predictor for the prognosis of specific cancers. The high expression of DKK1 may promote tumour metastasis in some cancers thereby worsening the prognosis of the patients. The above preliminary results from the study look quite interesting in GEA patients who have high expression of DKK1 biomarker regardless of their PD-L1 status. Additionally, it can be stated that the combination of DKN-01 and tislelizumab therapy was successful enough to generate early deep responses in the first-line patients with GEA. With these early results, it would be quite unfair to comment anything about its realistic anti-tumour activity in the future but DelveInsight remains quite optimistic about the clinical efficacy of the drug and still waits for the matured data readouts.

*SD= Stable disease, ORR=Objective response rate, PD= Progressive disease, OS= Overall survival, PFS= Progression-free survival, CR= Complete response, PD= Partial response, TRAE= treatment-related adverse event, AE= Adverse events, DoR=Duration of response, RE =Response evaluable, GEA= gastroesophageal adenocarcinoma, LOT=Line of therapy, CPS=combined positive score