ASCO GU 2019: CheckMate 9UT - Nivolumab or Nivo Plus BMS-986205 with or without Intravesical Bacillus Calmette-Guerin in BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer

San Francisco, CA ( Immune checkpoint inhibitors, including the anti-PD1 monoclonal antibody nivolumab, have demonstrated favorable tolerability and efficacy profiles, ushering a new treatment paradigm for advanced bladder cancer. Nivolumab has a meaningful clinical benefit in patients with advanced bladder cancer, whose disease progressed or recurred following treatment with platinum-based chemotherapy (objective response rate of 20%), and a manageable safety profile. However, an unmet need exits for new effective treatment options in an earlier stage of the disease, including patients with BCG-unresponsive, high risk- non-muscle invasive bladder cancer (NMIBC). 

Indoleamine 2,3-dioxygenase 1 (IDO1) allows tumor immune escape through kynurenine production, which stimulates activation of regulatory T cells and suppresses effector T cell proliferation. Concurrent IDO1 inhibition and PD-1 pathway blockade may have the potential to drive synergistic antitumor effects, decreasing kynurenine levels, and increasing cytotoxic T-cell proliferation within tumors. BMS-986205 is a selective potent once-daily oral IDO1 inhibitor, which has demonstrated clinical activity in combination with nivolumab in patients with immunotherapy-nave advanced bladder cancer who received >=1 prior line of therapy.

In this presented phase 2 open-label study (Clinical trial information: NCT03519256), using a novel adoptive type design, the authors plan to assess the efficacy and safety of nivolumab +/- BMS-986205 +/- intravesical BCG via randomization of patients to 4 treatment arms (Figure 1). The key inclusion and exclusion criteria are noted in Figure 2. The primary endpoint of the study is the proportion of CIS patients with complete response, duration of complete response, and event-free survival for non-CIS patients. The secondary endpoints include progression-free survival, adverse events, and incidence of laboratory abnormalities.

The study has begun recruiting in 15 countries worldwide with a target of 436 patients, and an estimated completion date in April 2023.

Presented by: Noah Hahn, MD, Johns Hopkins University School of Medicine, Baltimore, MD

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA