AMG 479, Amgen Corporation‘s investigational, fully human, monoclonal antibody targets signaling through type 1 insulin-like growth factor receptor, which plays an important role in the regulation of cell growth and survival. In a randomized, open-label, Phase 2 study, co-administration of AMG479 and gemcitabine resulted in a median OS of 7.3 months vs. 6.2 months in the gemcitabine arm (HR=0.69, 95% CI: 0.38–1.25; P=0.22).8 Patients receiving AMG 479 also experienced longer PFS of 5.1 months vs. 2.1 months (HR=0.60; 95% CI: 0.36–1.01; P=0.055).

AMG 479 is currently being investigated in Phase 3 trials.9 In this multicenter, randomized, double-blind, placebo-controlled trial that will evaluate AMG 479 or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas, gemcitabine is administered on Days 1, 8, and 15 of a 28-day cycle, AMG 479 or placebo is administered on Days 1 and 15 of the 28-day cycle, both are administered IV. The primary purpose of the study is to determine if AMG 479 and gemcitabine improves OS as compared to placebo and gemcitabine. Patients included in the trial have untreated metastatic adenocarcinoma of the pancreas; adequate hematologic, renal and liver function; and an ECOG rating of 0 or 1. Patients were excluded if they had prior chemotherapy or radiotherapy for pancreatic cancer, central nervous system metastases, or external biliary drain. Phase 3 data collection is expected to be completed in October 2013.

Continue Reading

The lethality of pancreatic cancer, as well as its associated drug resistance, prompts the necessity of constant clinical drug development. Novel anti-tumor agents are filling the current pancreatic cancer pipeline with hope for longer patient survival. From chemotherapeutic agents to novel biologicals, there are promising treatment options on the horizon.   

1. Pharmacyclics Corporation. Factor VIIa inhibitor for oncology and thrombosis. Accessed May 21, 2012.

2. Pharmacyclics Corporation. Factor VIIa inhibitor program. Accessed May 21, 2012.

3. United Stated National Institutes of Health. Study of safety and tolerability of PCI-27483 in patients with pancreatic cancer patients receiving treatment with gemcitabine. Accessed May 21, 2012.

4. Ramanathan R.K., Gressler V., Shah S., et al. Phase I/II study of PCI-27483, a coagulation Factor VIIa (FVIIa) inhibitor, in advanced pancreatic cancer patients receiving treatment with gemcitabine. Poster presented at: American Society of Clinical Oncology.  Gastrointestinal Cancers Symposium; January 20-22, 2011; San Francisco, CA. Accessed May 21, 2012.  

5. Le DT, Lutz E, Huang L, et al. Phase 1b study of ipilimumab alone or in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in pancreatic cancer. Presented at: American Society of Clinical Oncology. 2012 Gastrointestinal Cancers Symposium; January 19–21, 2012; San Francisco, CA. Accessed May 21, 2012.

6. Lutz E., Yeo C.J., Lillemoe K.D., et al. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma: a phase II trial of safety, efficacy, and immune activation. Ann Surg. 2011;253(2):328-335.

7. United States National Institutes of Health. Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Undergoing Chemotherapy and Radiation Therapy for Stage I or Stage II Pancreatic Cancer That Can Be Removed by Surgery. Accessed May 21, 2012.

8. New AMG 479 phase 2 data show antitumor activity in patients with metastatic pancreatic cancer [press release]. Thousand Oaks, CA: Amgen Inc.; June 4, 2010. Accessed May 21, 2012.

9. United States National Institutes of Health. GAMMA – gemcitabine and AMG 479 in metastatic adenocarcinoma of the pancreas. Accessed May 21, 2012.