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Additional file 2: Figure S2. Function of YAP/TAZ expression in HuH-28 and G415 cells

Additional file 3: Figure S3. Expression analysis of CCA cell lines after YAP/TAZ inhibition

Additional file 4: Suppl. Table S1. iCCA, dCCA and pCCA cohorts

Additional file 5: Suppl. Table S2. Primers and antibodies used in this study

Figure S1. Example of a typical staining pattern of on-slide control tissues (PD-L1, SP263). Tonsillary crypt epithelium showed strong membranous immunoreactivity (black triangle), while immune cells in germinal centers were weakly positive (black arrow, A). Gallbladder epithelium (black triangle) was negative but occasionally few immune cells were positive (black arrow, B). (PPTX 2692 kb)

Figure S1. Histology of the detected MSI gallbladder carcinoma. High magnification pictures of Hematoxylin & Eosin (HE) stained full-slide sections of the detected MSI GBC show a typical glandular, tubular, acinar, ductal morphology of pancreatobiliary subtype (A: original magnification: 200x and B: 400x). (DOCX 348 kb)

3099 Background: NTRK gene fusions, coding for chimeric TRK proteins, are oncogenic drivers in many solid tumors. In an integrated analysis of three phase 1/2 trials (ALKA-372-001 [EudraCT 2012-000148-88]; STARTRK-1 [NCT02097810]; STARTRK-2 [NCT02568267]), entrectinib, a potent CNS-active TRK inhibitor, showed durable systemic and intracranial responses in pts with NTRK-fp solid tumors. We report updated data from a larger cohort with longer follow-up (clinical cutoff 2 Aug 2021). Methods: Pts with locally advanced/metastatic NTRK-fp solid tumors and ≥12 months’ follow-up from first tumor assessment were efficacy evaluable. The safety cohort also included pts from TAPISTRY (NCT04589845). Tumor responses were assessed by blinded independent central review (BICR) per RECIST v1.1 at Week 4 and every 8 weeks thereafter. Primary endpoints: objective response rate (ORR) and duration of response (DoR). Progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR and safety were also assessed. Results: The efficacy-evaluable cohort comprised 150 adults (vs 121 previously) with 17 different solid tumor types. Median age was 58.5 years; 91% of pts had ECOG PS 0–1 and 37% had received ≥2 prior lines of therapy. Median survival follow-up was 30.6 months. ORR was 61.3% (n = 92/150; 95% CI: 53.1–69.2), including 25 complete responses. Responses were observed in all tumor types with n>1 (Table). Median DoR, PFS and OS were 20.0 months (95% CI 13.2–31.1), 13.8 months (95% CI 10.1–20.0), and 37.1 months (95% CI 27.2–not estimable [NE]), respectively. In pts with and without investigator-assessed baseline CNS metastases (n = 31 / n = 119), ORR was 61.3% (95% CI 42.2–78.2) and 61.3% (95% CI 52.0–70.1) respectively. IC-ORR was 69.2% (n = 9/13) in pts with BICR-assessed measurable CNS metastases; median IC-DoR was 17.2 months (7.4–NE). In the safety population (N = 235: all treated pts), most treatment-related adverse events (TRAEs) were grade 1/2 and not serious; the most frequent were dysgeusia (36.6%), diarrhea (29.8%) and weight increase (28.5%). TRAEs led to dose interruption, reduction and discontinuation in 32.8%, 24.3% and 7.2% of pts, respectively. Conclusions: In this updated analysis, entrectinib continued to demonstrate deep and durable responses and was well tolerated in pts with NTRK-fp solid tumors with or without baseline CNS metastases. Clinical trial information: STARTRK-2 [NCT02568267]. [Table: see text]

Figure S1. Histology of the detected MSI gallbladder carcinoma. High magnification pictures of Hematoxylin & Eosin (HE) stained full-slide sections of the detected MSI GBC show a typical glandular, tubular, acinar, ductal morphology of pancreatobiliary subtype (A: original magnification: 200x and B: 400x). (DOCX 348 kb)