Introduction & Objectives: Docetaxel or the next-generation hormonal agents (NHAs) abiraterone and enzalutamide are the standard of care for patients with adenocarcinoma mCRPC but are not curative. Approximately 20% of patients develop t-NE after treatment for adenocarcinoma mCRPC, which is associated with shorter survival and has no standard of care. The vascular endothelial growth factor (VEGF)/fibroblast growth factor receptor (FGFR) inhibitor lenvatinib inhibits proliferation and angiogenesis in adenocarcinoma prostate cancer cells in vitro and in mice. In the phase 2 KEYNOTE-199 trial, pembrolizumab monotherapy showed promising antitumor activity in docetaxel-pretreated patients with adenocarcinoma mCRPC. VEGF/FGFR inhibition combined with PD-1 inhibition may have enhanced benefit in adenocarcinoma mCRPC and, in addition, may provide a new treatment option for t-NE mCRPC.
Materials & Methods: KEYNOTE-365 (NCT02861573) is a nonrandomized, open-label, multicohort, phase 1b/2 trial conducted to evaluate different pembrolizumab combination therapies in several patient populations with mCRPC. Cohort E will enroll patients with confirmed adenocarcinoma of the prostate without small cell histology per investigator. Cohort F will enroll patients with t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review). Each cohort will include patients with prior docetaxel treatment for mCRPC. Prior treatment with ≤2 NHAs (for hormone-sensitive metastatic prostate cancer [mHSPC] or mCRPC) and 1 other chemotherapy for mCRPC is permitted. Additionally, enrollment in cohort F requires prostate cancer progression within <6 months of starting an NHA (for mHSPC or mCRPC) and within <6 cycles of docetaxel for mCRPC. Each cohort will enroll 40-100 patients with Eastern Cooperative Oncology Group performance status score of 0 or 1. Both cohorts will receive pembrolizumab 200 mg IV every 3 weeks (Q3W) + oral lenvatinib 20 mg once daily until disease progression, withdrawal of consent, prespecified alanine aminotransaminase or aspartate aminotransaminase elevation, or other discontinuation event. CT or MRI will be performed at screening, Q9W through week 54, and Q12W thereafter. Adverse events (AEs) will be monitored throughout the trial through 30 days after discontinuation (90 days for serious AEs), graded using the CTCAE v4.0. Primary end points are safety and tolerability, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points include time to PSA progression; ORR and radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 by BICR; duration of response and disease control rate per RECIST v1.1 and PCWG3-modified RECIST v1.1 by BICR; and overall survival.
Results: KEYNOTE-365 is currently enrolling in Australia, Germany, New Zealand, Spain, and the United States.
Conclusions: Results from cohorts E and F of KEYNOTE-365 will provide a preliminary estimate of the efficacy and safety of pembrolizumab combined with lenvatinib in adenocarcinoma and t-NE mCRPC.

KEYNOTE-365 Cohorts E and F: Phase 1b/2 Study of Pembrolizumab + Lenvatinib Combination Therapy in Patients With Adenocarcinoma Metastatic Castration-Resistant Prostate Cancer (mCRPC) or Treatment-Emergent Neuroendocrine mCRPC (t-NE)

For 2021, our focus remains: turning new data into your daily practice. The programme will consist of state-of-the-art lectures, case discussions and panel debates. Our faculty is a group of international & multidisciplinary experts.

We will take you on our journey to Ghent and beyond. Prior the congress, we send out case challenges, where you can compare your opinion with peers & experts. These cases will be part of the Global Congresses on Prostate & Bladder Cancer programme during the congress days (12 & 13 October for PROSCA and 14 & 15 October for BLADDR). After these days, you will be updated on prostate & bladder cancer management.