Response Rates Show Promise in Phase 1 trial Involving ASCT in Metastatic PDAC

Kenneth H. Yu, MD, a gastrointestinal medical oncologist from Memorial Sloan Kettering Cancer Center, spoke with CancerNetwork® regarding results from the phase 1 SHARON trial (NCT04150042).1 The trial aimed to assess melphalan, BCNU, hydroxocobalamin (B12), and ascorbic acid, followed by autologous stem cell transplant for patients with stage IV pancreatic ductal adenocarcinoma (PDAC) or breast cancer who have BRCA1/2 or PALB2 mutations.

Here, Yu focuses on the response rates and efficacy noted in the trial, which were presented at the European Society for Medical Oncology Congress 2025.Topline data showed that the median progression-free survival was 14.2 months.

Yu goes on to discuss the response rates and how they are comparable to other trials and outcomes in the space, including the phase 3 POLO trial (NCT02184195), which looked at olaparib (Lynparza) for patients with pancreatic cancer with germline BRCA mutations who have not progressed on the first-line platinum-based chemotherapy.2

Transcript:

The best reference study is the POLO trial, which was looking at patients who, after getting platinum chemotherapy, received a PARP inhibitor or olaparib. In that trial, patients who were responding to platinum [therapy had a] progression-free survival of about 7.5 months. In [the SHARON] trial, we looked at not just patients who were responsive to platinum [therapy], but also patients who were progressing; our trial also enrolled patients with more aggressive disease. On average, these patients had received 3 lines of therapy, and in POLO, it was just the 1 line of [platinum] therapy. We looked at 2 different cohorts. This was mostly a safety trial, but we were also trying to look at whether there was a signal for efficacy.

In all comers, the patients did well. It’s a short duration of follow-up, but on average, patients are living more than 3 years. In the POLO trial, the median overall survival is only about 20 months. Even in our group of patients who had more aggressive disease, the overall survival number looked to be comparable, if not a little bit better, numerically. When we just looked at the group of patients who would be similar to the patients in the POLO trial, our progression-free survival number was about 14.2 months. That compares favorably to the 7.5 months seen in the POLO trial. In that subset of patients who were still responding to therapy at the time that they enrolled, overall survival was good. All those patients are still alive. We haven’t reached a median overall survival number.

Looking at response rates. Looking at those patients who were not progressing on therapy when they enrolled in the study, the best response seen in all of them was either a partial response or stable disease. There was a 100% disease control rate, which is excellent. We have 2 patients who remain free of progression off treatment after the transplant. That’s about a 40% durable response rate free of disease.

We’ve learned a couple of things. First, the transplant seemed to be very safe in patients who have had these BRCA mutations and who [undergo] the transplants. They all tolerate the transplant well. We’re seeing a good efficacy signal, particularly in patients who are not progressing when they enrolled in the study; patients who were progressing through prior chemotherapy do not seem to have as durable a response. That’s not so surprising, and for future enrollment in the study, and for further development, we will probably focus on patients who are not progressing on chemotherapy, and trying to see whether the transplants can help those patients more.

Reference

1. Yu KH, Dahi PB, Weekes CD, et al. The SHARON trial: melphalan, BCNU, hydroxocobalamin, ascorbic acid, and stem cells for pancreatic and breast cancer and an inherited BRCA/PALB2 mutation. Presented at the European Society for Medical Oncology Congress 2025; October 17-21, 2025. Berlin, Germany. Abstract 2228P.
2. Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381(4):317-327. doi:10.1056/NEJMoa1903387