Enrolment has stopped in one of two global Phase III studies evaluating necitumumab (IMC-11F8, Eli Lilly and Company and Bristol-Myers Squibb Company), a fully-human IgG1 monoclonal antibody which binds to the epidermal growth factor receptor (EGFR), as a first-line treatment for advanced non-small cell lung cancer (NSCLC). The primary reason to stop one of the trials is safety concerns about blood clots in people who received the drug.
Necitumumab inhibits downstream targets in the EGFR pathway (Mitogen-activated protein or MAP kinases), which are important for cellular proliferation, differentiation, invasion and metastasis. Additionally, as an IgG1 construct, necitumumab can induce antibody-dependent cell-mediated cytotoxicity against tumor cells.
The randomized, multi-center, open-label Phase III trial, named INSPIRE (NCT00982111), is evaluating the addition of necitumumab, to a combination of pemetrexed ( Alimta?, Eli Lilly and Company) and cisplatin compared to a regimen of pemetrexed and cisplatin, as a first-line treatment for patients with advanced nonsquamous NSCLC. No new safety issues were seen in the control arm with pemetrexed and cisplatin.
The decision to stop enrollment followed an independent Data Monitoring Committee (DMC) recommendation that no new or recently enrolled patients continue treatment in the trial because of safety concerns related to thromboembolism (blood clots) in the experimental arm of the study. The DMC also noted that patients who have already received two or more cycles of necitumumab appear to have a lower ongoing risk for these safety concerns. These patients may choose to remain on the trial, after being informed of the additional potential risks. Investigators will continue to assess patients after two cycles to determine if there is a potential benefit from treatment.
Necitumumab continues to be studied in a Phase III trial named SQUIRE (NCT00981058). This study is evaluating necitumumab as a potential treatment for a different type of lung cancer called squamous non-small cell lung cancer in combination with gemcitabine HCl (Gemzar? , Eli Lilly and Company) and cisplatin. The same independent DMC recommended that this trial continue because no safety concerns have been observed.”Patient safety is paramount. While stopping enrollment in one of the two Phase III trials is disappointing, the SQUIRE Phase III study of necitumumab in lung cancer continues,” said Richard Gaynor, M.D., vice president, oncology product development and medical affairs for Lilly. “Lilly remains committed to developing new medicines that can help treat this devastating disease.”
Lilly has contacted all trial investigators to provide detailed information on how to manage individuals enrolled in the trial, and has notified all pertinent regulatory agencies of this decision.
Necitumumab is being developed in a partnership between Lilly and Bristol-Myers Squibb. The two companies share development costs and any potential commercialization within the U.S., Canada and Japan, while Lilly has exclusive commercialization rights in all other countries.
A separate Phase I trial (NCT01088464) designed to establish the safety and pharmacokinetic profile of necitumumab administered either in a 3-week cycle or in a 2-week cycle to Japanese patients with advanced solid tumors who have not responded to standard therapy or for whom no standard therapy is available is ongoing. This trial is expected to enroll a maximum of 18 patients.
For more information:
First-line Treatment of Patients With Stage IV Nonsquamous Non-Small Cell Lung Cancer With Necitumumab (IMC-11F8) and Pemetrexed-Cisplatin (INSPIRE)
First-line Treatment of Participants With Stage IV Squamous Non-Small Cell Lung Cancer With Necitumumab and Gemcitabine-Cisplatin (SQUIRE)
Study of IMC-11F8 in Patients With Advanced Solid Tumors (NCT01088464)