Pfizer Halts Phase III Figitumumab Trial In NSCLC, But Other Studies Go On
This article was originally published in Pharmaceutical Approvals Monthly
Executive Summary
News that Pfizer was discontinuing a Phase III study of the insulin growth factor-1 receptor inhibitor figitumumab in non-small cell lung cancer didn't come as much of a surprise Dec. 30. The firm had already announced in October it was suspending patient enrollment after more participants died following treatment with the drug than without
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News that Pfizer was discontinuing a Phase III study of the insulin growth factor-1 receptor inhibitor figitumumab in non-small cell lung cancer didn't come as much of a surprise Dec. 30. The firm had already announced in October it was suspending patient enrollment after more participants died following treatment with the drug than without. Nonetheless, it marks a setback for Pfizer and its push into oncology, especially since figitumumab is one of the company's lead programs and management was quite excited about it. In 2008, when Pfizer unveiled its new oncology business unit at the American Society of Clinical Oncology meeting, figitumumab was one of the bright late-stage stars Pfizer pointed to in its pipeline (1 (Also see "With A Novel Pipeline, Pfizer Tries A New Oncology Business Unit Too" - Pink Sheet, 23 Jun, 2008.)). The news could also prompt concern elsewhere in the industry, given that IGF-1R inhibition is an emerging area of oncology research, one many drug makers are honing in on - and making a significant investment in. IGF-1R has been identified as a drug target because of its involvement in the growth and proliferation of a variety of cancers and because it is thought to protect tumors from apoptosis associated with cytotoxic agents and EGFR inhibitors. Pfizer had been leading the pack with figitumumab; the drug was the first IGF-1R inhibitor into the clinic and the first to enter Phase III trials (2 (Also see "Pfizer’s IGF-1 Inhibitor Leads Pack In Phase III For NSCLC" - Pink Sheet, 1 May, 2008.)). Pfizer's decision to discontinue the A4021016 trial comes after an independent Data Safety Monitoring Committee found the addition of figitumumab to paclitaxel plus carboplatin would be unlikely to meet the study's primary endpoint of improving overall survival compared to paclitaxel plus carboplatin alone. In September, the DSMC found an imbalance in serious adverse events in the treatment arms, including fatalities. The trial was studying figitumumab as a first-line treatment in patients with advanced non-adenocarcinoma non-small cell lung cancer. The Phase III failure highlights the obstacles in developing novel cancer drugs, particularly in the notoriously challenging area of lung cancer. Clinical trials in NSCLC have about a 90 percent failure rate. However, data from a Phase II study presented at ASCO in 2008 showed that figitumumab in first-line NSCLC in combination with paclitaxel and carboplatin had higher objective response rates for the combination compared to chemotherapy alone (54 percent versus 41 percent). Based on that robust Phase II data, Pfizer initiated a large Phase III global registration trial for figitumumab called ADVIGO (ADVancing IGF-1R in Oncology). The program comprises three studies and was intended to enroll more than 2,000 patients. In addition to the now defunct ADVIGO 1016 study, the program includes ADVIGO 1018, comparing figitumumab with OSI's Tarceva (erlotinib) versus erlotinib alone in non-adenocarcinoma patients who have failed prior platinum-based chemotherapy, and ADVIGO 1017, using Lilly's Gemzar (gemcitabine) and cisplatin and enrolling previously untreated patients with different histologies of NSCLC. Figitumumab Development To Continue In NSCLC The 1018 trial is ongoing, while Pfizer said it plans to forge on with the 1017 trial, incorporating lessons learned from the 1016 trial into the design. Thus Pfizer is not giving up on figitumumab in NSCLC, although the future development plan hinges on finding the right patients who can benefit from treatment. "While these findings are disappointing, Pfizer is committed to using information gained from this study to refine the design of future trials of figitumumab in NSCLC," the company said. "We are hopeful that we will be able to identify a subset of patients who may have derived benefit from the addition of figitumumab to chemotherapy. If this can be done, then future trials will focus on this group of patients in our efforts to deliver this drug to the right patient." Pfizer is also studying the IGF-1R candidate to treat prostate and breast cancer and Ewing's sarcoma. Among the other companies that have IGF-1R drugs in mid- to late-stage development in oncology are Eli Lilly, which jumped into the field with its acquisition of ImClone in 2008, when the company gained IMC-A12 (now called cixutumumab). During Lilly's R&D update in December, the company said it is currently studying cixutumumab in Phase II in breast, prostate, colorectal, liver, neuroendocrine and head and neck cancers, as well as sarcoma. Phase III trials are expected to begin in various tumor types in 2010. Amgen and Merck both have IGF-1R inhibitors in Phase II development in cancer. OSI Pharmaceuticals is developing OSI-906 in Phase III for adrenocortical carcinoma and in Phase I/II in ovarian cancer. Earlier this year, as part of a pipeline overhaul, Sanofi-Aventis returned rights to its Phase II anti-IGF-1R oncologic to ImmunoGen (3 (Also see "Sanofi Cuts Development Of 14 Drugs In First Quarter, With More R&D Changes To Come" - Pink Sheet, 29 Apr, 2009.)). - Jessica Merrill ( 4 [email protected] ) |