A phase I study to assess the safety and tolerability of intravesical pembrolizumab in recurrent non-muscle invasive bladder cancer (NMIBC)
| العنوان: | A phase I study to assess the safety and tolerability of intravesical pembrolizumab in recurrent non-muscle invasive bladder cancer (NMIBC) |
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| المؤلفون: | Jeremy Crew, Mariolina Salio, Karin Purshouse, Mark R. Middleton, Andrew Protheroe, Caroline Haddon, Victoria K Woodcock, Gillian Verrall, Leena Elhussein, Chrissie Butcher, Vincenzo Cerundolo |
| المصدر: | Journal of Clinical Oncology. 37:406-406 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Cancer Research, medicine.medical_specialty, Bladder cancer, business.industry, Urology, Pembrolizumab, medicine.disease, Phase i study, 03 medical and health sciences, 0302 clinical medicine, Oncology, Tolerability, 030220 oncology & carcinogenesis, medicine, Intravesical bcg, Local immunity, business, Intermediate risk, Non muscle invasive, 030215 immunology |
| الوصف: | 406 Background: Intravesical BCG has been the mainstay of therapy following TURBT for intermediate risk NMIBC for many years and is thought to act through activation of non-specific local immunity. With the recent success of checkpoint inhibitor treatment in metastatic bladder cancer, we sought to investigate the anti-PD1 inhibitor pembrolizumab as a potential agent for use in patients with intermediate risk NMIBC in a phase I/II study. The primary aim of the phase I safety run-in was to assess the safety and tolerability of intravesical pembrolizumab after TURBT in patients with intermediate risk NMIBC. Methods: Eligible patients had recurrent NMIBC for which adjuvant treatment post TURBT was a reasonable treatment option, ECOG PS 0-1 and adequate end organ function. Pembrolizumab was administered by intravesical instillation once weekly for a total of 6 doses. Intra-patient dose escalation was performed in three paired patient cohorts with doses starting at 50mg and increasing through 100mg to a maximum of 200mg. Adverse events (AEs) were assessed using CTCAE v4.03 with dose limiting toxicity (DLT) defined as a clinically significant, drug related, grade 4 haematological or ≥ grade 3 non-haematological toxicity occurring within 7 days of administration of the first treatment at a given dose for that patient. Results: In the first 4 patients treated, no DLTs were seen during dose escalation. Drug-related AEs included Grade 1 dysuria, fatigue and nausea. Grade 1-2 urinary tract infections, Grade 1 cystitis and Grade 3 urosepsis (SAE) were observed but assessed as probably not related to pembrolizumab. Recruitment of a final cohort of two patients at repeated doses of 200mg is ongoing to confirm safety and tolerability of this dose. Conclusions: Administration of intravesical pembrolizumab was safe and well tolerated in patients with NMIBC following TURBT. A randomised, parallel group, phase II marker-lesion study to assess the safety, efficacy and tolerability of either intravesical pembrolizumab or intravenous pembrolizumab in a larger cohort of patients with intermediate risk recurrent NMIBC is planned. Clinical trial information: NCT03167151. |
| تدمد: | 1527-7755 0732-183X 0316-7151 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::461e7a935e42dd32524c1985ecaedc72Test https://doi.org/10.1200/jco.2019.37.7_suppl.406Test |
| رقم الانضمام: | edsair.doi...........461e7a935e42dd32524c1985ecaedc72 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X 03167151 |
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