Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer progressing on enzalutamide: cohorts 4 and 5 of the phase 2 KEYNOTE-199 study.

Background: KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.

Methods: Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines.

Application of estimand framework to the design and analysis of multi-regional clinical trials.

With the increasing globalization of drug development and the publication of the International Council for Harmonisation (ICH) E17 guideline (ICH International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 2017), multi-regional clinical trials (MRCTs) have become a preferred option to accelerate the availability of new medical products by design, execution and simultaneous submission under one protocol. MRCTs, with the participation of all major regions including countries from both developed and emerging markets, surely make new drug development more efficient. Even though the proposed estimand framework (ICH E9 (R1) (2019), came later in 2019 and was not mentioned in ICH E17, the application of the estimand framework has the potential to enhance the design, execution, and analysis in MRCTs.

KEYNOTE-991: pembrolizumab plus enzalutamide and androgen deprivation for metastatic hormone-sensitive prostate cancer.

Current treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC) delays disease progression and improves survival, but resistance is inevitable. Additional therapies that prolong survival are needed. Androgen deprivation therapy (ADT) combined with next-generation hormonal agents, such as enzalutamide, is standard-of-care for men with mHSPC.

Pembrolizumab in Chinese patients with advanced melanoma: 3-year follow-up of the KEYNOTE-151 study.

Unlabelled: Survival is generally poor for Chinese patients with advanced melanoma because of high rates of acral and mucosal melanoma and limited therapeutic options. The first analysis of the phase 1b KEYNOTE-151 study showed second-line pembrolizumab was well tolerated and had clinically meaningful antitumor activity in Chinese patients with advanced melanoma. Three-year follow-up is presented.

Standard-Dose Pembrolizumab Plus Alternate-Dose Ipilimumab in Advanced Melanoma: KEYNOTE-029 Cohort 1C, a Phase 2 Randomized Study of Two Dosing Schedules.

Purpose: Standard-dose pembrolizumab plus alternative-dose ipilimumab (1 mg/kg Q3W for 4 doses) were tolerable and had robust antitumor activity in advanced melanoma in cohort B of the phase 1 KEYNOTE-029 study. Cohort C evaluated standard-dose pembrolizumab with two other alternative ipilimumab regimens.

Patients And Methods: Patients with treatment-naive unresectable stage III/IV melanoma were randomly assigned 1:1 to pembrolizumab 200 mg Q3W for ≤24 months plus ipilimumab 50 mg Q6W for 4 doses (PEM200+IPI50), or the same pembrolizumab regimen plus ipilimumab 100 mg Q12W for 4 doses (PEM200+IPI100).