On July 23, 2018 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, reported it has entered into a collaboration agreement with Merck KGaA, Darmstadt, Germany, and Pfizer to evaluate Leap’s GITR agonist, TRX518, in combination with avelumab*, a human anti-PD-L1 IgG1 monoclonal antibody, and chemotherapy (Press release, Leap Therapeutics, JUL 23, 2018, View Source;p=RssLanding&cat=news&id=2359396 [SID1234528762]).
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Under the terms of the collaboration, Leap will be conducting a Phase I/II clinical trial in advanced solid tumors including expansion populations in patients with relapsed/refractory ovarian, breast, and prostate cancers. The study is expected to begin enrolling patients in the first quarter of 2019.
"The combination of TRX518 with anti-PD-L1 immunotherapy and cyclophosphamide has a solid scientific rationale and we look to build upon our early clinical and preclinical data highlighting the potential benefits of such a combination," commented Cynthia Sirard, M.D., Vice President, Clinical Development of Leap Therapeutics.
"TRX518 has demonstrated encouraging potential with early clinical activity in patients with advanced solid tumors," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "This collaboration with Leap Therapeutics to evaluate TRX518 in combination with avelumab gives us the opportunity to investigate a potential novel immunotherapy treatment regimen as we pursue our mission of improving outcomes for patients living with hard-to-treat cancers."
"Combination therapy remains a major focus in our clinical development program for avelumab in an effort to advance the treatment landscape for patients with challenging cancers," said Alise Reicin, Head of Global Clinical Development at the Biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. "Through our collaboration with Leap Therapeutics, we are eager to further understand the potential of this novel immunotherapy combination in this patient population."
Avelumab has received accelerated approval** by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC), and is under further clinical evaluation across a range of tumor types under a global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.
*Avelumab is under clinical investigation for treatment of solid tumors and hematological malignancies in combination with TRX518 and has not been demonstrated to be safe and effective for these uses. There is no guarantee that avelumab will be approved for solid tumors or hematological malignancies by any health authority worldwide.
About Avelumab
Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.1-3 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.3-5 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.
Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including seven Phase III trials, and over 8,600 patients across more than 15 different tumor types. For a comprehensive list of all avelumab trials, please visit clinicaltrials.gov.
Approved Indications in the US**
The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) mMCC in adults and pediatric patients 12 years and older and (ii) patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications were approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
Important Safety Information from the US FDA Approved Label
The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.
For full prescribing information and medication guide for BAVENCIO, please see www.BAVENCIO.com.
Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.