On September 21, 2021 Nektar Therapeutics (NASDAQ: NKTR) reported it has entered into a new oncology clinical collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc. to evaluate the maintenance regimen of NKTR-255, Nektar’s interleukin-15 (IL-15) receptor agonist, in combination with avelumab, a PD-L1 inhibitor, in patients with locally advanced or metastatic urothelial carcinoma (UC) in the Phase II JAVELIN Bladder Medley study (Press release, Nektar Therapeutics, SEP 21, 2021, View Source [SID1234590105]).
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NKTR-255 is wholly owned by Nektar and is currently being evaluated in two separate clinical studies in both liquid and solid tumors. The novel IL-15 agonist is designed to activate the IL-15 pathway to expand both natural killer (NK) cells and memory CD8+ T cell populations.1 Avelumab, which is marketed in the U.S. as BAVENCIO, is co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer Inc.
"We are excited to partner with Merck KGaA, Darmstadt, Germany and Pfizer Inc. to evaluate the combination of NKTR-255 with avelumab in urothelial carcinoma," said Jonathan Zalevsky, Ph.D., Chief Research & Development Officer at Nektar. "Preclinical studies suggest that avelumab may induce lysis of tumor cells via antibody-dependent cell-mediated cytotoxicity, or ADCC, indicating an additional mechanism of action, and providing an opportunity for potential synergy when combined with an NK cell stimulator, such as NKTR-255."
Under the new collaboration, Merck KGaA, Darmstadt, Germany and Pfizer Inc. will include the combination of NKTR-255 plus avelumab in the new JAVELIN Bladder Medley study. The study is a recently designed global, multi-center Phase II umbrella trial evaluating different avelumab-based combinations, compared with avelumab monotherapy, as potential maintenance therapy regimens for patients with locally advanced or metastatic UC that has not progressed with a first-line platinum-containing chemotherapy regimen. Nektar will supply NKTR-255 for the trial. Nektar and the Merck KGaA, Darmstadt, Germany-Pfizer alliance will each maintain existing global commercial rights to their respective medicines. The study is expected to begin enrolling patients in the first quarter of 2022.
BAVENCIO (avelumab) is indicated in the U.S. and Europe for the maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.
NKTR-255 is an investigational agent in clinical development and is not approved alone or in combination with avelumab (or any other agent) for use in any country.
About Urothelial Carcinoma
Bladder cancer is the 10th most commonly diagnosed cancer worldwide, with approximately 573,000 new cases and 213,000 deaths.2 It is more common in men than in women, representing the 6th most common cancer and the 9th leading cause of cancer death among males. Incidence rates for men and women are respectively 9.5 and 2.4 per 100,000. Mortality rates for men and women are respectively 3.3 and 0.9 per 100,000.2 Noninvasive cancers reflect a large proportion of all bladder cancers2, and only 25% to 55% of patients receive any second-line therapy after first-line chemotherapy.3-9 In the U.S. and EU5 markets, approximately 40% to 50% of patients receive an immune checkpoint inhibitor in second-line therapy.10
BAVENCIO Important Safety Information from the US FDA-Approved Label
The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis and hepatitis [including fatal cases], colitis, endocrinopathies, nephritis, and other immune-mediated adverse reactions as a single agent or in combination with axitinib [which can be severe and have included fatal cases]), infusion-related reactions, hepatotoxicity in combination with axitinib, major adverse cardiovascular events (MACE) in combination with axitinib [which can be severe and have included fatal cases], and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO monotherapy include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction peripheral edema, decreased appetite, urinary tract infection and rash. Common adverse reactions (reported in at least 20% of patients) in patients receiving BAVENCIO in combination with axitinib include diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain and headache. Grade 3-4 hematology laboratory value abnormalities reported in at least 10% of patients with Merkel cell carcinoma treated with BAVENCIO monotherapy include lymphopenia; in patients receiving BAVENCIO in combination with axitinib, grade 3-4 clinical chemistry abnormalities include blood triglyceride increased and lipase increased.
For full US Prescribing Information and Medication Guide for BAVENCIO, please see View Source
About NKTR-255
NKTR-255 is a novel polyethylene glycol (PEG)-conjugate of recombinant human interleukin-15 (rhIL-15), which was designed to retain all known receptor binding interactions of the IL-15 molecule. The investigational candidate is uniquely designed to overcome known challenges of recombinant IL-15 and other IL-15 agonists, which are rapidly cleared from the body and have shown diminishing response to successive doses. Through an extended circulating half-life and optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances functional NK cell populations and formation of long-term CD8+ mediated immunological memory, which may lead to sustained anti-tumor immune response.