Eli Lilly and Co.'s $1.48 billion acquisition of Armo Biosciences Inc., intended to broadly bolster its immuno-oncology program, fell short of that goal in its first big test, a phase III trial in second-line pancreatic cancer called Sequoia. Investigators combined the deal's star asset, pegilodecakin, with 5-FU, leucovorin and oxaliplatin (FOLFOX) – a widely accepted second-line treatment for patients who've progressed after a first-line gemcitabine-containing regimen – and compared it to treatment with FOLFOX alone. The pegilodecakin combo failed to outperform FOLFOX in overall survival (OS), the trial's primary endpoint, while also being associated with higher rates of neutropenia, thrombocytopenia, fatigue and anemia compared to the FOLFOX-only arm.

Lilly declined BioWorld's invitation to further describe the trial's outcome Wednesday or the candidate's future in pancreatic cancer. But the company was clearly aware of the challenges it faces with the molecule. At the recent World Conference on Lung Cancer in Barcelona, Spain, the firm's chief scientific officer, Daniel Skovronsky, called it "a higher-risk opportunity," but one that's "also a potentially high-reward immuno-oncology bet." A few weeks later, in the Lilly Oncology Update conference call held at the European Society of Medical Oncology Congress (ESMO), pegilodecakin got no mention at all, in clear contrast to Lilly's more recent acquisition, Loxo Oncology Inc. (See BioWorld, Jan. 8, 2019.)

Still, another important readout for the program, the results of dual phase II trials testing pegilodecakin with checkpoint inhibitors in non-small-cell lung cancer (NSCLC), is expected to arrive in early 2020. Meanwhile, "for the next stage of pegilodecakin's clinical development, Lilly is focused on assessing biomarkers and conducting studies in NSCLC and other tumor types, including renal cell carcinoma (RCC), where the molecule has shown promising activity," the company said. Details of the RCC studies will be posted to Clinicaltrials.gov in the first half of 2020, Lilly spokeswoman Tracy Henrikson said.

Sequoia was initiated by Armo in March 2017 based on results of the phase I/Ib Ivy study, which evaluated pegilodecakin as a single agent and in combination with chemotherapy and with checkpoint inhibitor therapy across multiple tumor types, including pancreatic, NSCLC and renal cell cancers. (See BioWorld, May 11, 2018.)

Armo enrolled 47 patients with advanced pancreatic ductal adenocarcinoma in Ivy, treating them with pegilodecakin alone (20 microg/kg) or pegilodecakin (5 microg/kg, qd) in combination with FOLFOX chemotherapy. At ESMO 2018, Ivy trial investigators reported that, in the pegilodecakin monotherapy arm, median progression-free survival (PFS) was 1.7 months vs. 2.7 months for patients provided with FOLFOX plus pegilodecakin. Median OS was 3.8 months on pegilodecakin monotherapy vs. 10.2 months on the combination.

Indianapolis-based Lilly purchased Armo in June 2018. At the time of the deal, Levi Garraway, the company's head of global oncology development and medical affairs, positioned it as just the kind of deal the company was looking for, one providing "a first-in-class opportunity or a distinct mechanism of action." Since then, Garraway has moved to Roche Holding AG. Pegilodecakin, a pegylated IL-10 receptor agonist and the only molecule of that class in development, according to Cortellis, provided that without doubt. But can it provide a return on Lilly's investment in NSCLC and RCC? Outcomes of Ivy recently reported in The Lancet Oncology say maybe.

Combining pegilodecakin with anti-PD-1 monoclonal antibodies Keytruda (pembrolizumab, Merck & Co. Inc.) and Opdivo (nivolumab, Bristol-Myers Squibb Co.) achieved measurable responses in patients previously treated for kidney and lung cancers, according to Aung Naing, an associate professor of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, lead author of The Lancet article. Objective responses were seen in 43% of NSCLC patients, 40% of kidney cancer patients and 10% of melanoma patients, the open-label trial showed.

Lilly's shares (NYSE:LLY), down 6.7% year-to-date, fell 1.6% to $107.95 on Wednesday. The company is scheduled to report and discuss its third-quarter earnings on Oct. 23.

Separately Wednesday, the Pharmaceutical Research and Manufacturers of America appointed Lilly CEO and Chairman David Ricks as its chairman-elect. And, on Monday, the company gained FDA approval for Reyvow (lasmiditan), the first FDA-approved medicine in a new class of acute migraine treatment. (See BioWorld, Oct. 15, 2019.)

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