770P - Neoadjuvant pembrolizumab in stage IV ovarian cancer: The phase II Neo-Pembro trial

Background

While immune checkpoint inhibitors (ICI) have revolutionized cancer care, their efficacy in ovarian cancer (OC) remains limited. Nevertheless, some patients (pts) demonstrate lasting clinical responses, emphasizing the need to understand how tumor microenvironment and molecular characteristics impact ICI response. Building on findings in other cancers, neoadjuvant ICI with induction chemotherapy may enhance tumor-specific T cell response and improve efficacy in OC.

Methods

33 previously untreated pts with stage 4 high grade serous OC received 6 cycles of carboplatin-paclitaxel and interval cytoreductive surgery after 3 cycles. Pembrolizumab (anti-PD1, Pem) was added from cycle 2 onward (200mg Q3W) and continued for 1 year. Biopsies were obtained at baseline, after 1 cycle of chemo and during surgery. Primary endpoint was dynamics of intratumoral immune response analyzed with multiplex immunofluorescence. Secondary endpoints were progression-free (PFS) and overall survival (OS), pathologic response (PR) and safety. PR was assessed using the Chemo Response Score (CRS), with major PR defined as CRS 3 and minor PR as CRS 1-2. Efficacy was compared to a historic cohort treated without Pem. HRs were estimated using Cox models.

Results

At 52.8 mo (IQR 34.5-62.6) follow-up, median PFS was 14.2 mo (95% CI 11.1-30.2) and median OS was 32.0 mo (95% CI 21.5-NR). 10 pts (30%, 95% CI 16-49) had a major PR and 9/10 were alive at data cutoff, including 6 without recurrence. In contrast, 4/23 pts with minor PR were alive (HR 0.06, 95% CI 0.01-0.48, p = 0.007). Major PR had significantly better OS compared to major PR in the historic cohort treated without Pem (median OS NR vs 21.4 mo, HR 0.11, 95% CI 0.01-0.93, p = 0.043). Adjusting univariable analyses for prognostic factors did not affect HRs. No new safety signals emerged. After chemo induction, PD-L1 expression was significantly higher in major PR. After chemo+Pem, major PR had significantly higher CD3⁺ + CD8⁺ T cell infiltration compared to minor PR.

Conclusions

Major responders show higher immune infiltration and PD-L1 expression after treatment with chemo+Pem and pathologic response was strongly associated with survival. Our data indicate that there is a subset of pts who could benefit from adding Pem in the neoadjuvant setting.

Clinical trial identification

NCT03126812.

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Netherlands Cancer Institute Merck Sharp & Dohme.

Disclosure

D. Van Den Broek: Non-Financial Interests, Institutional, Non financial benefits, Outside the submitted work: Delfi Diagnostics. G.S. Sonke: Financial Interests, Institutional, Research Funding, Outside the submitted work: Agendia, AstraZeneca, Novartis, Seagen, Roche; Financial Interests, Institutional, Research Funding: Merck. All other authors have declared no conflicts of interest.