Lilly and Merck Expand Immuno-oncology Collaboration with Phase III Nonsquamous Non-Small Cell Lung Cancer Trial

Eli Lilly and Company LLY and Merck MRK, known as MSD outside the United States and Canada, today announced the extension of an existing collaboration to evaluate the safety and efficacy of the combination of Lilly's ALIMTA(R) (pemetrexed for injection) and Merck's KEYTRUDA(R) (pembrolizumab) in a pivotal Phase III study in first-line nonsquamous non-small cell lung cancer (NSCLC). The study will be sponsored by Merck and will be open to patients with NSCLC in the first-line setting, regardless of PD-L1 status. Financial details of the collaboration were not disclosed. The expansion of this oncology clinical trial collaboration comes following the release of encouraging data from a Phase I study, presented earlier this year at the 16(th) World Congress on Lung Cancer, which evaluated pemetrexed, carboplatin and pembrolizumab in first-line nonsquamous NSCLC. Pemetrexed is a leading therapeutic option used in combination with platinum-based therapies in this setting, making it an ideal candidate for combination studies with immunotherapy treatments. Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body's immune system to help detect and fight tumor cells. Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells -- and is currently approved as a single-agent therapy for certain types of NSCLC. "The extension of our immuno-oncology collaboration with Merck reinforces our combination-focused strategy, which we believe has the potential to help this patient population where there is a significant unmet need," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "Building upon this scientific partnership represents our shared, strong commitment to improve the lives of those living with cancer." "Based on the data for ALIMTA, we believe this collaboration with Lilly has great potential to help even more patients," said Roger Dansey, M.D., therapeutic area head and senior vice president, oncology late stage development, Merck Research Laboratories. "We look forward to continuing our collaboration with Lilly across all of these trials -- including the registrational Phase III all-comers trial for NSCLC." In addition to the studies of pemetrexed and pembrolizumab in first-line nonsquamous NSCLC, other ongoing trials from the original agreement between Lilly and Merck, through a subsidiary, include: -- A Phase I/II study examining the combination of ramucirumab with pembrolizumab in multiple tumors. -- A Phase I/II study examining the combination of necitumumab with pembrolizumab in NSCLC. NOTES TO EDITORS About KEYTRUDA(R) (pembrolizumab) Injection 100 mg KEYTRUDA is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. KEYTRUDA is also indicated at the same dosing for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. These indications are approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for these indications may be contingent upon verification and description of clinical benefit in the confirmatory trials. Selected Important Safety Information for KEYTRUDA(R) (pembrolizumab) Pneumonitis, including fatal cases, occurred in patients receiving KEYTRUDA. Pneumonitis occurred in 12 (2.9%) of 411 melanoma patients, including Grade 2 or 3 cases in 8 (1.9%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Pneumonitis occurred in 19 (3.5%) of 550 patients with NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis in patients, receiving KEYTRUDA. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis. Colitis (including microscopic colitis) occurred in 4 (1%) of 411 patients with melanoma, including Grade 2 or 3 cases in 1 (0.2%) and 2 (0.5%) patients, respectively, receiving KEYTRUDA. Colitis occurred in 4 (0.7 %) of 550 patients with NSCLC, including Grade 2 (0.2%) or 3 (0.4%) colitis in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis. Hepatitis occurred in patients receiving KEYTRUDA. Hepatitis (including autoimmune hepatitis) occurred in 2 (0.5%) of 411 patients with melanoma, including a Grade 4 case in 1 (0.2%) patient, receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA. Hypophysitis occurred in 2 (0.5%) of 411 patients with melanoma, including a Grade 2 case in 1 and a Grade 4 case in 1 (0.2% each) patient, receiving KEYTRUDA. Hypophysitis occurred in 1 (0.2 %) of 550 patients with NSCLC, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or Grade 4 hypophysitis. Hyperthyroidism occurred in 5 (1.2%) of 411 patients with melanoma, including Grade 2 or 3 cases in 2 (0.5%) and 1 (0.2%) patients, respectively, receiving KEYTRUDA. Hypothyroidism occurred in 34 (8.3%) of 411 patients with melanoma, including a Grade 3 case in 1 (0.2%) patient, receiving KEYTRUDA. Hyperthyroidism occurred in 10 (1.8%) of 550 patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%). Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC, including Grade 2 (5.5%) or 3 (0.2%). Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 hyperthyroidism. Type 1 diabetes mellitus, including diabetic ketoacidosis, has occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia. Nephritis occurred in patients receiving KEYTRUDA. Nephritis occurred in 3 (0.7%) patients with melanoma, consisting of one case of Grade 2 autoimmune nephritis (0.2%) and two cases of interstitial nephritis with renal failure (0.5%), one Grade 3 and one Grade 4. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis. Other clinically important immune-mediated adverse reactions can occur. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement of the adverse reaction to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following steroid taper. Permanently discontinue KEYTRUDA for any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction. Across clinical studies with KEYTRUDA, the following clinically significant, immune-mediated adverse reactions have occurred: bullous pemphigoid and Guillain-Barré syndrome. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of patients with melanoma treated with KEYTRUDA: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients with NSCLC treated with KEYTRUDA: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis. Infusion-related reactions, including severe and life-threatening reactions, have occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of infusion related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For severe or life-threatening reactions, stop infusion and permanently discontinue KEYTRUDA.