Pegilodecakin Falls Short in Phase III Pancreatic Cancer Trial

Maura Dickler, MD, vice president, late phase development, Lilly Oncology

Maura Dickler, MD

Combining the pegylated IL-10 pegilodecakin with FOLFOX (folinic acid, 5-FU, oxaliplatin) chemotherapy did not improve overall survival (OS) as a second-line therapy for patients with metastatic pancreatic cancer, according to topline results from the phase III SEQUOIA trial.¹

Lilly Oncology, the company developing pegilodecakin, plans to submit the safety and efficacy data from the trial at an upcoming medical conference.

"Pancreatic cancer has proven to be one of the most difficult tumor types to treat and there have been very few recent treatment advancements in the later-line metastatic setting. We are grateful to the patients, investigators, and researchers who participated in the study," Maura Dickler, MD, vice president, late phase development, Lilly Oncology, said in a press release.

"While we are disappointed by the outcome of the SEQUOIA study, we look forward to the upcoming results in lung cancer, learning from those results and increasing our understanding of pegilodecakin's novel mechanism of action in cancer immunotherapy," added Dickler.

The global, multicenter, randomized phase III SEQUOIA trial included 567 patients with metastatic adenocarcinoma of the pancreas with disease progression after first-line treatment with a gemcitabine-containing regimen. Patients were randomized to FOLFOX alone or in combination with pegilodecakin. Overall survival was the primary endpoint.

Grade 3/4 adverse events that occurred at a ≥5% higher rate in the pegilodecakin versus the FOLFOX-alone arm included neutropenia, thrombocytopenia, fatigue, and anemia.

The SEQUOIA trial was launched following positive data from the phase I/Ib IVY study, which explored pegilodecakin as monotherapy and combined with chemotherapy or immunotherapy across several solid tumor types, including pancreatic cancer, non—small cell lung cancer, and renal cell carcinoma.

Data from the IVY trial were presented at the 2018 ESMO Congress for a subgroup of 25 heavily pretreated patients with pancreatic ductal adenocarcinoma.² The patients were treated with pegilodecakin (5.0 µg/kg) plus FOLFOX. Twenty-one patients had not received a prior platinum-based regimen and had progressed on a gemcitabine-containing regimen. The median number of prior therapies was 2 (range, 1-5). The median follow-up was 26.4 months (range, 22-32).

Among 19 evaluable patients, the objective response rate (ORR) was 15.8%, including 2 (10.5%) complete responses and 1 partial response. The disease control rate was 73.7%. The median progression-free survival and median OS were 2.6 and 10.2 months, respectively. The 1- and 2-year OS rates were 42.9% and 28.6%, respectively.

In the safety population, which included all 25 patients, grade 3/4 treatment-related adverse events included thrombocytopenia (56%), anemia (44%), neutropenia (36%), leukopenia (12%), and fatigue (12%). Sixteen percent of patients had grade 1/2 neuropathy, but there were no reported cases of grade 3/4 neuropathy.

"More than 56,700 Americans—mothers, daughters, fathers, sons, colleagues and friends—will be diagnosed with pancreatic cancer this year alone," Julie Fleshman, JD, MBA, president and CEO of the Pancreatic Cancer Action Network (PanCAN), said in the press release. "Because this is an aggressive disease and the current scope of treatment options is limited, there remains an urgent need for meaningful solutions to improve outcomes for pancreatic cancer patients."

References

1. Lilly announces phase 3 study in patients with metastatic pancreatic cancer did not meet primary endpoint of overall survival. Posted October 16, 2019. Accessed October 16, 2019. https://prn.to/2VMNc2p.
2. Hecht JR, Naing A, Falchook GS, et al. Responses and durability of clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients treated with pegilodecakin (AM0010) in combination with 5-FU/LV and oxaliplatin (FOLFOX). Ann Oncol. 2018;29(8 suppl, abstr 1143P). doi: 10.1093/annonc/mdy288.016.