Andrew J. Armstrong, MD, MSc, discusses study of chemoimmunotherapy in NEPC/AVPC

In this video, Andrew J. Armstrong, MD, MSc, discusses findings from the phase 2 CHAMP trial (NCT04709276), which evaluated the addition of dual immune checkpoint blockade with ipilimumab (Yervoy) and nivolumab (Opdivo) to platinum-doublet chemotherapy in patients with neuroendocrine prostate cancer (NEPC) or aggressive-variant prostate cancer (AVPC).¹ These findings were presented at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

Armstrong is medical oncologist at Duke Cancer Center and a professor of medicine at Duke University in Durham, North Carolina.

The CHAMP trial was designed to address a significant unmet need in NEPC and AVPC, which Armstrong noted are biologically aggressive forms of prostate cancer characterized by low androgen receptor activity, low prostate-specific antigen levels, visceral metastases, and poor responses to conventional therapies. Historically, platinum-based doublet chemotherapy has been the standard treatment approach, but responses are often short-lived, with progression-free survival (PFS) typically lasting less than 6 months.

In this multicenter phase 2 study, investigators evaluated a quadruplet regimen consisting of cabazitaxel, carboplatin, ipilimumab, and nivolumab. The study enrolled 40 patients across 3 centers within the Department of Defense Prostate Cancer Clinical Trials Consortium, including patients with histologic, clinical, or molecular features of NEPC or AVPC. The primary end point was immune-modified radiographic PFS (rPFS) assessed by iRECIST/PCWG3 criteria.

The trial met its primary end point, demonstrating a 6-month rPFS rate of 74%, exceeding the historical benchmark of 55% associated with cabazitaxel plus carboplatin alone (90% CI, 63 to 100; P = .013). Median immune-modified rPFS reached 12 months (95% CI, 9.1 to 14). Objective responses were observed in 37% of patients (95% CI, 22 to 54), and the regimen produced several notably durable responses, including 2 patients who remained disease-free and off therapy beyond 30 months. Armstrong highlighted that some patients experienced pseudoprogression before ultimately responding to treatment, underscoring the importance of using immune-modified response criteria in future studies of chemoimmunotherapy for this population.

According to the authors, the combination demonstrated acceptable tolerability given the high-risk nature of the disease, with no treatment-related deaths reported. Common grade 3 to 4 adverse events included anemia, neutropenia, sepsis, thrombocytopenia, colitis, febrile neutropenia, and urinary tract infections. Armstrong noted that chemotherapy could be discontinued early in responding patients, allowing maintenance treatment with immunotherapy alone.

Looking ahead, he emphasized the need for larger randomized studies to confirm the benefit of chemoimmunotherapy in NEPC and AVPC, similar to the trials that established this approach in small cell lung cancer. He also highlighted emerging investigational strategies, including next-generation checkpoint inhibitors, T-cell engagers, and radioligand therapies, as promising avenues for future research in this biologically distinct subset of prostate cancer.

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