공시 • Oct 18
Daiichi Sankyo And AstraZeneca Present Initial Results For DATROWAY Plus Rilvegostomig Combination Therapy in Urothelial Cancer
Daiichi Sankyo and AstraZeneca presented initial results from one sub-study of the TROPION-PanTumor03 phase 2 trial showing that DATROWAY (datopotamab deruxtecan) plus rilvegostomig showed promising tumor responses and disease control as first-line and second-line combination therapy in patients with locally advanced or metastatic urothelial cancer. DATROWAY is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. Rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody. In a sub-study of patients with locally advanced or metastatic urothelial cancer, DATROWAY plus rilvegostomig was evaluated in both the first-line and second-line treatment settings. As first-line treatment for patients not eligible for cisplatin (n=22), DATROWAY plus rilvegostomig demonstrated a confirmed objective response rate (ORR) of 68.2% (95% confidence interval [CI]: 45.1-86.1) and a disease control rate (DCR) of 95.5% (80% CI: 83.4-99.5). Median progression free survival (PFS) was not reached in the first-line setting and the PFS rate was 73.5% (95% CI: 46.5-88.4) at 12 months. As second-line treatment for patients who previously received platinum-based chemotherapy and no prior treatment with immunotherapy (n=18), DATROWAY plus rilvegostomig demonstrated a confirmed ORR of 38.9% (95% CI: 17.3-64.3) and a DCR of 83.3% (80% CI: 66.6-93.7). Median PFS was 12.5 months (95% CI: 4.2-NR) and the PFS rate was 60.0% (95% CI: 33.7–78.7) at 12 months. Median duration of response (DoR) was not yet reached in either setting. The safety profile of DATROWAY plus rilvegostomig was consistent with the known safety profiles of each agent. Grade 3 or higher treatment-related adverse events (TRAEs) were observed in four of 22 patients (18.2%) receiving first-line treatment and in seven of 18 patients (38.9%) receiving second-line treatment. The most common grade 3 or higher TRAEs occurring in patients treated with DATROWAY plus rilvegostomig in the first-line (n=22) and second-line (n=18) settings, respectively, were increased amylase (13.6%, 16.7%), neutropenia (4.5%, 5.6%), stomatitis (0%, 5.6%), decreased appetite (0%, 5.6%) and anemia (0%, 5.6%). There was one (4.5%) interstitial lung disease (ILD) event adjudicated as drug-related in first-line and two (11.1%) in second-line setting with no grade 3 or higher ILD events observed. Daiichi Sankyo has initiated the TROPION-Urothelial03 phase 2/3 trial evaluating DATROWAY plus platinum-based chemotherapy compared to gemcitabine and platinum-based chemotherapy in patients with metastatic urothelial carcinoma following progression during or after treatment with enfortumab vedotin in combination with pembrolizumab. In TROPION-PanTumor03, patients were enrolled across seven sub-studies that evaluated DATROWAY as monotherapy or in combination with other approved or investigational cancer medicines. In a sub-study evaluating patients with locally advanced or metastatic urothelial cancer (sub-study 6, cohort 6B [n=40]), patients received DATROWAY in combination with rilvegostomig in either the first-line setting (cisplatin ineligible patients with no prior systemic therapy, or progression more than 12 months after neoadjuvant or adjuvant therapy) or the second-line setting (previous platinum-based chemotherapy in the locally advanced or metastatic setting, or progression less than 12 months after platinum-based neoadjuvant or adjuvant therapy). Of the second-line patients who were not previously treated with immunotherapy (n=18), six had previous treatment in the adjuvant or neoadjuvant setting with progression within 12 months and 12 had been treated in the metastatic setting. Median duration of follow-up was 10.8 months and 9.7 months in the first-line and second-line setting, respectively. Summary of Sub-study 6, Cohort 6B of TROPION-PanTumor03 Efficacy Results: Efficacy Measure First-Line Subset (n=22) Second-Line Subset (n=18) Confirmed ORR,(%) (95% CI) 68.2% (45.1–86.1) 38.9% (17.3–64.3) CR, n (%) 1 (4.5%) 0 PR, n (%) 14 (63.6%) 7 (38.9%) SD, n (%) 6 (27.3%) 8 (44.4%) PD, n (%) 1 (4.6%) 3 (16%) DCR at 12 weeks, (%) (80% CI) 95.5% (83.4–99.5) 83.3% (66.6–93.7) DoR, median(months) (95% CI) NR (9.4 months–NR) NR (6.9 months–NR) PFS median (months) (95% CI) NR (10.8 months–NR) 12.5 months (4.2 months–NR) CI, confidence interval; CR, complete response; DCR, disease control rate; DoR, duration of response; NR, not reached; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease ORR is CR+ PR As assessed by investigator Patient has no post-baseline assessment and died less than 13 weeks after first dose Proportion of patients who had achieved a CR or PR in the first 13 weeks or who had SD for at least 11 weeks after start of treatment as assessed by investigator. TROPION-PanTumor03 is a global, multicenter, multi-cohort, open-label, phase 2 trial evaluating the efficacy and safety of DATROWAY as monotherapy and in combination with various approved or investigational cancer medicines across seven sub-studies in several metastatic solid cancers, including endometrial, gastric, prostate, ovarian, colorectal, urothelial and biliary tract cancer. Cohort 6B is evaluating DATROWAY (6 mg/kg) plus rilvegostomig as first-line and second-line combination therapies in patients with locally advanced or metastatic urothelial cancer. The primary endpoint is ORR as assessed by investigator as well as safety and tolerability. Secondary endpoints include investigator-assessed DCR, DoR, PFS as assessed by investigator as well as pharmacokinetics. TROPION-PanTumor03 will enroll approximately 580 patients across all sub-studies in Asia, Europe and North America. Rilvegostomig is AstraZeneca’s PD-1/TIGIT bispecific antibody. The TIGIT component of rilvegostomig is derived from the clinical-stage anti-TIGIT antibody, COM902, developed by Compugen Ltd.
