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12-04-2021 | Oncology | News | Article

AACR 2021

mCRPC with immunogenic signature may respond to nivolumab plus ipilimumab

Author:
Laura Cowen

medwireNews: Combination therapy with nivolumab and ipilimumab has shown antitumor activity in a phase 2 study of men with metastatic castration-resistant prostate cancer (mCRPC) and a positive immunogenic signature (ImS+).

Data from the NEPTUNES trial were presented by Mark Linch, from the University College London Cancer Institute in the UK, at the virtual AACR Annual Meeting 2021.

Linch and team screened 184 men with mCRPC that had progressed following at least one line of therapy and found that 62 (34%) were ImS+. These individuals had at least one of either DNA mismatch repair deficiency (MMRD), DNA damage repair deficiency excluding MMRD, or a high level (>20%) of tumor infiltrating lymphocytes (TILs).

Of the ImS+ men, 35 were treated with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles, followed by nivolumab 480 mg every 4 weeks for up to 1 year.

During a median 7.2 months of follow-up, 10 patients had either a radiologic response, a prostate-specific antigen (PSA) response of at least 50%, conversion of circulating tumor cells (CTC) at 9 weeks, or a combination of the three, giving a composite response rate (CRR) of 28.6%.

Linch told delegates that this was “numerically higher than other CPI [checkpoint inhibitor] studies in prostate cancer” but noted that two more responses were needed to reject the null hypothesis that the CRR was at or below 20%.

In spite of this, 70% of responders had an ongoing response at 12 months, the median overall survival was around 18 months, and the median progression-free survival was approximately 5 months.

When the researchers analyzed the response criteria separately, the PSA response rate was 22.9%, while the radiologic and CTC response rates were 11.4% each. Of note, three of the four patients with a CTC response also had a PSA response.

Linch and team also looked at the response rates according to a number of biomarkers and found that responses were enriched among patients with MMRD or BRCA1/2 mutations. Specifically, four of five patients with MMRD and three of four of those with BRCA1/2 mutations responded to treatment. Conversely, there were no responses among individuals with ATM, CHD1, or CHEK2 mutations.

He said: “Further study of nivolumab plus ipilimumab in biomarker selected patients with mCRPC is warranted.”

Linch reported that the safety profile of the combination therapy was “consistent with other studies using this treatment schedule.” Serious adverse reactions occurred in 57% of patients, and were most commonly gastrointestinal events, particularly diarrhea. Four patients had pneumonitis and there were no treatment-related deaths.

However, only 31% of participants completed all four cycles of combination therapy, which suggests “that alternative dosing schedules may be required,” Linch remarked.

He concluded that accrual to cohort 2, which will test nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, is underway and that that translational biomarker analysis is ongoing.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

AACR Annual Meeting 2021; 10–15 April

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