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Background: FGFR alterations are reported across various malignancies and might act as oncogenic drivers in multiple histologies. Erdafitinib is an oral, selective pan-FGFR tyrosine kinase inhibitor with activity in FGFR-altered advanced urothelial carcinoma. We aimed to evaluate the safety and activity of erdafitinib in previously treated patients with FGFR-altered advanced solid tumours. Methods: The single-arm, phase 2 RAGNAR study was conducted at 156 investigative centres (hospitals or oncology practices that are qualified oncology study centres) across 15 countries. The study consisted of four cohorts based on tumour histology and patient age; the results reported in this Article are for the primary cohort of the study, defined as the Broad Panel Cohort, which was histology-agnostic. We recruited patients aged 12 years or older with advanced or metastatic tumours of any histology (except urothelial cancer) with predefined FGFR1–4 alterations (mutations or fusions according to local or central testing). Eligible patients had disease progression on at least one previous line of systemic therapy and no alternative standard therapy available to them, and an Eastern Cooperative Oncology Group performance status of 0–1 (or equivalent for adolescents aged 12–17 years). Patients received once-daily oral erdafitinib (8 mg/day with provision for pharmacodynamically guided up-titration to 9 mg/day) on a continuous 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate by independent review committee according to Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, or Response Assessment In Neuro-Oncology (RANO). The primary analysis was conducted on the treated population of the Broad Panel Cohort. This ongoing study is registered with ClinicalTrials.gov, number NCT04083976. Findings: Patients were recruited between Dec 5, 2019, and Feb 15, 2022. Of 217 patients treated with erdafitinib, 97 (45%) pa

AIM: To evaluate the diagnostic value of spectral detector computed tomography (SDCT)-derived iodine overlay maps and low-energy virtual mono-energetic images (VMI) for the initial locoregional assessment of primary, therapy-naive head and neck cancer. MATERIALS AND METHODS: Fifty-six patients with histologically confirmed untreated squamous cell carcinoma of the head and neck who underwent SDCT of the neck for staging purposes were included in this retrospective study. Attenuation, image noise as well as signal-and contrast-to-noise ratios (S-/CNR) in VMI40-70keV were obtained from region of interest (ROI)-based measurements in the tumour and important anatomical landmarks (sternocleidomastoid muscle, subcutaneous fat, thyroid gland, submandibular gland, carotid artery, and jugular vein). Tumour conspicuity and delineation, as well as subjective image quality, were rated for conventional images, VMI40-70keV, and iodine overlay maps using five-point Likert scales. RESULTS: The CNR of the tumour versus the floor of the mouth and the CNR of the tumour versus the sternocleidomastoid muscle was significantly higher in VMI40keV in comparison to conventional images (10.0 f 7.3 versus 3.8 f 3.3 and 11.3 f 7.6 versus 3.6 f 2.8; p<0.05 each). This was supported by qualitative results, as tumour conspicuity and delineation received superior ratings in iodine overlay maps and VMI40keV compared to conventional images (5 [3-5] and 5 [4-5] versus 3 [2-5]; 5 [2-5] and 5 [3-5] versus 3 [2-4], respectively, all p<0.05). VMI40keV yielded the highest score among all included image reconstructions for overall image quality (p<0.05 all). CONCLUSION: Iodine overlay maps and low-energy VMI derived from SDCT improve initial assessment of primary squamous cell carcinoma of the head and neck compared to conventional images. (c) 2022 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

Background The programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) axis plays a central role in suppressing antitumor immunity; axis dysregulation can be used by cancer cells to evade the immune system. Tislelizumab, an investigational monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to Fc 3R on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The aim of this phase IA/IB study was to investigate the safety/tolerability, antitumor effects and optimal dose and schedule of tislelizumab in patients with advanced solid tumors. Methods Patients (aged >=18 years) enrolled in phase IA received intravenous tislelizumab 0.5, 2, 5 or 10 mg/kg every 2 weeks; 2 or 5 mg/kg administered every 2 weeks or every 3 weeks; or 200 mg every 3 weeks; patients in phase IB received 5 mg/kg every 3 weeks. Primary objectives were to assess tislelizumab's safety/tolerability profile by adverse event (AE) monitoring and antitumor activity using RECIST V.1.1. PD-L1 expression was assessed retrospectively with the VENTANA PD-L1 (SP263) Assay. Results Between May 2015 and October 2017, 451 patients (n=116, IA; n=335, IB) were enrolled. Fatigue (28%), nausea (25%) and decreased appetite (20%) were the most commonly reported AEs. Most AEs were grade 1-2 severity; anemia (4.9%) was the most common grade 3-4 AE. Treatment-related AEs led to discontinuation in 5.3% of patients. Grade 5 AEs were reported in 14 patients; 2 were considered related to tislelizumab. Pneumonitis (2%) and colitis (1%) were the most common serious tislelizumab-related AEs. As of May 2019, 18% of patients achieved a confirmed objective response in phase IA and 12% in phase IB; median follow-up duration was 13.6 and 7.6 months, respectively. Pharmacokinetics, safety and antitumor activity obtained from both phase IA and IB determined the tislelizumab recommended dose; ultimately, tislelizumab

Background: Tislelizumab, a humanized IgG4 monoclonal Ab with high affinity and specificity forPD-1, was engineered to minimize binding to FcgammaRonmacrophages, thus abrogating antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports fromthis first-in-human study (NCT02407990), and other early phase studies, suggested tislelizumab was generally well tolerated and had antitumor activity in pts with advanced solid tumors.Here we report the effects of tislelizumab in a subset of pts enrolled in phase 1A/1B. Method(s): Eligible patients with advanced esophageal [EC], gastric [GC], hepatocellular [HCC], and non-small cell lung [NSCLC] cancers were treated with tislelizumab 2 or 5 mg/kg every 2 wks or 3 wks (Q3W); 97% received 5mg/kg Q3W. Adverse events (AEs) were assessed per NCI-CTCAE 4.03 criteria and tumor assessments performed every 9 wks using RECIST v1.1. Result(s): Of the 207 pts (EC=54; GC=54; HCC=50; NSCLC=49), 114 were male 111 were Asian, 78 were Caucasian and all but one received>=1 prior anticancer therapy. Treatment-related AEs (TRAEs) occurring in >=5% of pts were fatigue (8.7%) decreased appetite (6.8%), rash (6.8%), hypothyroidism(6.3%), and nausea (6.3%). Grade >=3 TRAEs occurring in >=2 pts were pneumonitis (n=3), elevated AST (n=3) and elevated ALT (n=2). Grade 5 TRAEs occurred in two pts: pneumonitis in a pt with NSCLC with compromised pulmonary function and acute hepatitis in a pt with HCC with rapidly progressing disease. As of 27 Apr 2018, a total of 23 pts remained on study treatment; median duration of study follow-up ranged from 4.9-9.9 mo. Responses in each tumor type are presented in the table. (Table Presented) Conclusion(s): Tislelizumab was generally well tolerated and antitumor activity was observed in each tumor type. Tislelizumab, as monotherapy and in combination, is being evaluated in multiple phase 2 and phase 3 studies.