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Association details:
| Biomarker: | DKK1 overexpression |
|---|---|
| Cancer: | Gastroesophageal Junction Adenocarcinoma |
| Drug: | Keytruda (pembrolizumab) (PD1 inhibitor) + sirexatamab (DKN-01) (DKK1 protein inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Safety, Efficacy, and Biomarker Results from a Phase Ib Study of the Anti-DKK1 Antibody DKN-01 in Combination with Pembrolizumab in Advanced Esophagogastric Cancers
Published date:
09/04/2021
Excerpt:
Sixty-three patients received DKN-01 150 mg (n = 2) or 300 mg (n = 61) plus pembrolizumab….Among response-evaluable anti-PD-1/PD-L1-naïve patients with GEJ/GC and known tumoral DKK1 expression, ORR was 50% in DKK1-high and 0% in DKK1-low patients, median PFS was 22.1 vs 5.9 weeks (HR: 0.24, 95% CI: 0.08-0.67), respectively, and median OS was 31.6 vs. 17.4 weeks (HR: 0.41, 95% CI: 0.16-1.07), respectively....Antitumor activity was enriched in anti-PD-1/PD-L1-naïve GEJ/GC patients whose tumors expressed high DKK1.
DOI:
10.1158/1535-7163.MCT-21-0273
Trial ID:
Source:
Title:
262 Tumoral DKK1 expression correlates with better clinical outcomes in patients with advanced esophagogastric cancer (EGC) treated with DKN-01
Published date:
11/09/2020
Excerpt:
69 EGC pts were enrolled to receive D alone or in combination with pac or pem and had tumoral DKK1 expression available. 59 pts had adenocarcinoma [19 esophageal (28%), 40 GEJ/gastric (58%)]...23 pts with DKK1 high (H-score ≥ upper-tertile [≥39]) had an ORR of 22% (5 PR/23), DCR of 57% (13/23) while DKK1 low (H-score <39) had an ORR of 2% (1/46) and DCR of 26% (12/46). Median PFS was 12.1 weeks in DKK1 high vs. 6.0 weeks in DKK1 low; HR of 0.58 (95%CI: 0.34, 1.0). Median OS was 31.6 weeks in DKK1 high vs. 18 weeks in DKK1 low; HR of 0.70 (95%CI: 0.38, 1.3). Subgroup of pts (n=9) with immune checkpoint inhibitor (ICI) refractory disease treated with D + pem demonstrated longer PFS and OS for DKK1 high pts (H-score ≥39, n=4) vs DKK1 low (n=5): PFS 12.8 weeks vs 6.0 weeks; HR of 0.16 (95%CI: 0.02, 1.5) and OS 46 weeks vs. 16 weeks, respectively; HR of 0.22 (95%CI: 0.03, 2.0). High levels of tumoral DKK1 expression correlate with improved clinical outcomes in heterogeneous EGC pts treated with D monotherapy or in combination.
DOI:
10.1136/jitc-2020-SITC2020.0262
Trial ID:
Title:
Tumoral DKK1 Expression Correlates with Better Clinical Outcomes in Patients with Advanced Esophagogastric Cancer (EGC) Treated With DKN-01
Published date:
11/09/2020
Excerpt:
In the study, high levels of tumoral DKK1 expression correlated with improved clinical outcomes in heterogeneous EGC patients treated with DKN-01 as monotherapy or in combination with pembrolizumab or paclitaxel. Pooled data for the 69 patients in the study for whom tumoral DKK1 expression data is available demonstrated that DKK1-high patients experienced higher overall response rates (ORR), a doubling of median progression-free survival (PFS), and longer median overall survival (OS) as compared to DKK1-low patients.
Trial ID:
