key: cord-0824431-5d360ptr authors: Albiges, L.; Schmidinger, M.; Taguieva-Pioger, N.; Perol, D.; Gruenwald, V. title: CaboPoint: A phase II study of second-line cabozantinib in patients with metastatic renal cell carcinoma (RCC) date: 2020-09-30 journal: Annals of Oncology DOI: 10.1016/j.annonc.2020.08.2075 sha: 2057a56b4a4c62f78dc0fa21276a131e455d1aac doc_id: 824431 cord_uid: 5d360ptr nan and peripheral blood inflammatory biomarkers with survival and response outcomes. The analysis of immune TME is conducted on two cohorts of mRCC patients treated with nivolumab as 2 nd line therapy: responders (PFS 12 months) and non-responders (PFS 3 months). It consists in the immunohistochemical, genomic and transcriptomic analysis of TME including morphological and immunophenotypic evaluation of tumor-infiltrating lymphocytes (TILs) (CD8+,CD4+, FOXP3+ T cells), tumor-associated macrophages polarization (pro-inflammatory M1 and anti-inflammatory M2 macrophages), tissue NLR and lymphocyte-to-monocyte ratio (LMR), population of NK cells and expression of the phosphorilated mTOR effectors S6K1 and 4E-BP. All the assessments of the immune TME are correlated, in terms of response and survival outcomes, with the peripheral blood biomarkers NLR, derived NLR [neutrophil / (white blood cells e neutrophils)], platelet-to-lymphocyte ratio (PLR), LMR and systemic inflammation index (SII; NLR x Platelets) at baseline and during the first four cycles of treatment. Legal entity responsible for the study: Giuseppe Fornarini. Background: Aged fragile patients are not usually included in clinical trials and efficacy and tolerability of the different treatments in this population are unknown. In the METEOR trial efficacy was similar in all age groups. Conversely, ageing has been associated with a decrease in the efficacy of immune checkpoint inhibitors due to immunosenescenc, thus, TKis might be a better treatment option. However, the absence of data and concerns about possible secondary effects associated, can preclude clinicians to treat aged fragile patients with cabozantinib. A pilot phase II trial would help to have data on safety and efficacy of cabozantinib in this aged fragile population. Trial design: Pilot open-label, multicenter study to evaluate cabozantinib safety and efficacy in previously untreated aged population with metastatic renal cell carcinoma. Patients will receive cabozantinib 40 mg p.o. once daily in 28-day cycles. Dose can be escalated to 60 mg to avoid suboptimal exposure to the drug if 40 mg is considered tolerated. Geratric evaluation scales will be performed to all patients and correlation between study outcomes and functionality, comorbidity and cognitive and social status will be evaluated. 50 patients is expected to be included in 2 years in ten spanish centers of SOGUG cooperative group. Trial design: CaboPoint (NCT03945773) is a phase II, open-label study of cabozantinib in adults with unresectable, locally advanced or metastatic clear-cell RCC, whose disease progressed after checkpoint inhibitor therapy with ipilimumab and nivolumab alone (cohort A) or in combination with VEGF-targeted therapy (cohort B). The primary endpoint is objective response rate. Secondary endpoints include time to response, duration of response, disease control rate, progression-free survival and overall survival. A target of 250 patients at 50 European sites will receive cabozantinib (60 mg once daily; self-administered at home) for 18 months after the last patient receives their first dose. Safety assessments will occur every 2 weeks up to week 4, then every 4 weeks. Patients may continue cabozantinib after disease progression if there is clinical benefit. During follow-up, patients who discontinue early will be contacted every 12 weeks to assess survival and subsequent therapy. Each cohort will have an interim analysis when 60% of patients reach 12 months of follow-up. CaboPoint has been adjusted to allow the trial to continue during the COVID-19 outbreak, protecting participants in compliance with the study protocol. 1 Alternative arrangements include: study drug dispensation to the participant's home if they cannot attend the study site; safety assessments at the study site or remotely at a local health care provider, within the protocol defined window; tumour assessments at a local radiology facility if they cannot attend the study site. Enrolment is permitted if the patient can be managed in compliance with the protocol and alternative arrangements. 1 The limitations, risks and impact on data privacy of such arrangements will be accounted for and documented. Clinical trial identification: NCT03945773. Editorial acknowledgement: Dr Tamzin Gristwood of Oxford PharmaGenesis, Oxford, UK, provided medical writing and editorial support, which was sponsored by Ipsen, in accordance with Good Publication Practice guidelines. Advisory/Consultancy, Travel/Accommodation/Expenses: EUSA; Honoraria (self), Advisory/Consultancy: Ipsen Advisory/Consultancy: Exelixis; Honoraria (self), Advisory/Consultancy: EISAI Advisory/Consultancy: Alkermes. N. Taguieva-Pioger: Full/Part-time employment: Ipsen. D. Perol: Honoraria (self Honoraria (self): BMS Honoraria (self): MSD Honoraria (self): Ipsen Honoraria (self): Pierre Fabre Honoraria (self): Novartis; Honoraria (self): Takeda Research grant/Funding (institution), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options: AstraZeneca; Honoraria (self) Research grant/Funding (institution), Shareholder/ Stockholder/Stock options: MSD Honoraria (self): Roche Research grant/Funding (institution), Travel/Accommodation/Expenses: Ipsen Travel/Accommodation/Expenses: Bayer; Honoraria (self) Honoraria (self): Janssen-Cilag Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer Honoraria (self): Lilly Honoraria (self): PharmaMar Research grant/Funding (institution): Novartis; Honoraria (self): EUSAPharm Honoraria (self): Eisai Legal entity responsible for the study: Ipsen.Funding: Ipsen.Disclosure: L. Albiges: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/ Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Merck; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Peloton Therapeutics; Advisory/ Consultancy: Corvus Pharmaceuticals. M. Schmidinger: Honoraria (self), Advisory/Consultancy, Travel/ Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/ Expenses: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: