Small Study Evaluates Novel Immunotherapeutic in Metastatic Pancreatic Cancer

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IN PATIENTS WITH metastatic pancreatic adenocarcinoma, 1-year survival reached 43% following treatment with a novel immunotherapy—PEGylated human IL-10 (AM0010, pegilodecakin)—plus chemotherapy, in a small study reported at the 2018 Gastrointestinal Cancers Symposium.1

“We saw a very high disease control rate, but what’s most interesting is the tail of the curve. We had patients staying on treatment for a long time.”
— J. Randolph Hecht, MD

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“We saw a very high disease control rate, but what’s most interesting is the tail of the curve,” said lead investigator J. Randolph Hecht, MD, of the University of California, Los Angeles, David Geffen School of Medicine. “With the caveat that patients who go on early-phase trials may not be representative of most second-line patients, we had patients staying on treatment for a long time.”

Pancreatic cancer has largely been refractory to immune-oncology approaches, and CD8 T cells are rare in most of these tumors. AM0010 is an immunotherapeutic that works differently from other immunotherapeutics now in use, Dr. Hecht explained.

Because this drug is synergistic with chemotherapy in preclinical models, the current study evaluated the combination as second-line and later treatment.

Closer Look at AM0010

IL-10 IS anti-inflammatory, and at higher concentrations and continuous exposure, it leads to the activation and expansion of antigen-activated CD8-positive T cells. AM0010 induces phosphorylation of STAT1 and STAT3 in CD8-positive T cells and increases the cytotoxicity, proliferation, and survival of intratumoral CD8-positive T cells and the persistence of antigen-activated CD8-positive T cells. In serum, AM0010 was shown to induce a comprehensive immune signature.


  • The novel therapeutic AM0010 works differently from checkpoint inhibitors, to which pancreatic cancer has been insensitive.
  • In a small study of 22 patients with metastatic pancreatic cancer, AM0010 plus FOLFOX led to a disease control rate of 74% and 1-year survival of 43%. Many patients remain on treatment.
  • A global phase III trial is underway.

“Compared to other immunotherapy agents, such as checkpoint inhibitors, PEGylated IL-10 works differently,” Dr. Hecht explained. “It activates preexisting T cells and allowing them to remain alive. It also has multiple effects on cytokines.”

Second-Line and Later Treatment

BECAUSE THIS drug was synergistic with chemotherapy in preclinical models and in the early clinical experience, the current study evaluated the AM0010-FOLFOX (leucovorin, fluorouracil, and oxaliplatin) combination as second-line and later treatment. The current study included patients with metastatic pancreatic cancer who were part of a large multicohort study of this agent in multiple malignant tumors. Patients had been previously treated with gemcitabine-containing regimens but had not received a platinum agent.

The monotherapy study included 22 patients who had received 3 to 7 lines of therapy. They received AM0010 at 20 μg/ kg subcutaneously every day. The combination study included 21 patients with disease progression after a median of 2 prior therapies (range, 1–5) who received AM0010 at 5 μg/kg daily plus FOLFOX.

As of October 29, 2017, 2 patients had remained on treatment for more than 1 year. Of 19 evaluable patients, 2 had an immune-related complete response, and 1 had an immune-related partial response. The overall response rate was 15.8%, and the disease control rate was 74%.

After a median follow-up of 20.3 months, median progression-free survival was 2.6 months, median overall survival was 10.2 months, and 1-year survival was 43% for patients receiving AM0010 plus FOLFOX (based on preclinical data of efficacy), Dr. Hecht reported. For AM0010 monotherapy, the disease control rate was 53%, and 1-year survival was 23%.

Remodeling of T-Cell Repertoire Correlated With Response

THE INVESTIGATORS compared T-cell clonality of pretreatment and on-treatment samples and found that expansion of novel T-cell clones (which were not detectable at day 1) correlated with objective response and appeared to correlate with survival of patients receiving AM0010 plus FOLFOX. Patients with longer survival also had a low expression of several key inflammation-related mRNAs.

“Transcriptional profiling and CD8-positive T-cell analysis in archival tumor tissue may identify those patients with longer overall survival time,” he said.


THE TREATMENT was well tolerated, with no autoimmune events observed with continuous dosing. Grade 3/4 anemia, however, was seen in 44% and thrombocytopenia, in 56%. These hematologic side effects were mitigated by dosing the drug 5 days on and 2 days off. With this schedule, there was no grade 3/4 anemia or thrombocytopenia, and the immune-stimulation profile was retained. Grade 3/4 neurotoxicity was not observed, despite 76% of patients having had gemcitabine and nab-paclitaxel in prior therapies.

The regimen is currently being studied in a phase III global clinical trial of 566 patients, in combination with FOLFOX (SEQUOIA), for which Dr. Hecht is the principal investigator. ■

DISCLOSURE: Dr. Hecht reported no conflicts of interest.


1. Hecht JR, Haing A, Falchook GS, et al: Overall survival of PEGylated human IL-10 (AM0010) with 5-FU/LV and oxaliplatin (FOLFOX) in metastatic pancreatic adenocarcinoma. 2018 Gastrointestinal Cancers Symposium. Abstract 374. Presented January 19, 2018.