Clinical Summary: 

• Design/Population: The randomized phase 2 S2001 trial evaluated olaparib plus pembrolizumab versus olaparib alone as maintenance therapy in patients with germline BRCA1- or BRCA2-mutated pancreatic cancer.
• Key Outcomes: The trial was stopped early for futility after failing to meet the prespecified progression-free survival improvement threshold. Olaparib plus pembrolizumab showed numerical improvements in response rate and progression-free survival compared with olaparib alone, suggesting preliminary clinical activity.
• Clinical Relevance: Olaparib plus pembrolizumab did not meet the efficacy bar for broad use in germline BRCA-mutated pancreatic cancer, but biomarker analyses may help identify subgroups more likely to benefit from PARP inhibitor and immune checkpoint inhibitor combination therapy.

Vincent Chung, MD, City of Hope, Duarte, California, presented results from the randomized phase 2 SWOG S2001 trial, which evaluated maintenance olaparib plus pembrolizumab versus olaparib alone in patients with germline BRCA1- or BRCA2-mutated pancreatic cancer. The study was developed through a collaborative effort involving SWOG, Alliance, ECOG-ACRIN, and NRG and sought to build on the established role of olaparib in this molecularly defined population.

The study did not meet its primary progression-free survival (PFS) end point and was stopped early for futility. Despite this, the combination demonstrated signs of clinical activity, including higher response rates and longer PFS than olaparib alone. Ongoing biomarker analyses using banked tissue and blood samples may help identify subsets of patients most likely to benefit from combining PARP inhibition with immune checkpoint blockade.

Dr Chung presented these results at the 2026 ASCO Annual Meeting in Chicago, Illinois.

Transcript: 

Hi, I'm Vincent Chung, I'm a medical oncologist at City of Hope in Duarte, California. The study I'll be presenting is S2001. S2001, this is a randomized phase 2 study of olaparib plus pembrolizumab versus olaparib alone in germline BRCA1 and BRCA2 mutated pancreatic cancer patients.

For this clinical trial, this is a very interesting clinical trial because I think one of the challenges that we've had in this disease is that as we all know, pancreatic cancer is a very lethal disease. We have seen that in germline BRCA1 and BRCA2-mutated pancreatic cancer patients. Lymparza is actually a standard maintenance therapy that's been approved based upon the POLO trial. This trial showed that there was an improvement in progression-free survival. However, there was no overall survival benefit in that trial. That kind of leads us to want to try to think about methods of potentially deepening and extending and sustaining that response. That's where this idea kind of came out.

What we do know is that with genomic instability, we do see that patients actually respond better to immune checkpoint inhibitors and that's what kind of led to this particular combination. PARP inhibitors in preclinical studies have shown that there's an increase upregulation of PD-L1 as well as an increase in the STEAM pathway activation. This therefore increases the cytotoxic T-cell infiltration within the tumor itself.

We have seen in preclinical models that we have had sustained responses in mouse models. Clinically, there was actually the POLAR trial, which was recently published. This actually looked at pembrolizumab plus olaparib in patients with BRCA1, BRCA2, as well as PAB2 mutations. They reported actually 35% response rates as well as overall survival about 28 months. This is very encouraging that we see that this combination is showing signs of activity. My clinical trial was actually, and this was developed in conjunction with Alliance. Michael Pishvaian is my co-PI for this study. This actually was really looking at the combination of olaparib with pembrolizumab versus olaparib alone. This was the first randomized clinical trial.

This was actually a very collaborative effort. This clinical trial was actually done in SWOG. We led the clinical trial. It was also done through Alliance as well as ECOG-ACRIN and NRG. It was really a team effort to really get this to the finish line and get this clinical trial completed.

We did have a very high bar for the clinical trial. We're looking to improve progression-free survival from seven months up to 11.7 months. We did have a futility analysis built into the clinical trial after about 50 events or 50% of the events. What we ended up seeing in this clinical trial was that the trial was actually closed early because we actually didn't meet that bar, but we did see that there were actually signs of activity.

The overall response rate was 28% compared to about 18% in the olaparib alone arm. The progression-free survival also increased from 6.4 months up to 8.2 months. We're seeing signs of clinical activity, but we didn't meet that bar of going from 7 all the way up to 11.7 months.

We did bank tissue as well as blood samples. It's going to be really important in terms of the correlative work to really look at that select population that may benefit from this particular type of therapy. We're going to be doing some ongoing biomarker analysis.

Source: 

Chung V, Guthrie KA, Pishvaian MJ, et al. Randomized phase II trial of olaparib and pembrolizumab vs olaparib alone as maintenance therapy in metastatic pancreatic cancer patients with germline BRCA1 or BRCA2 (gBRCA1/2) mutations: SWOG S2001. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 4012.