Leap Therapeutics is launching a Phase 1/2 clinical trial to test its immunotherapy TRX518 in combination with Bavencio (avelumab) and chemotherapy in advanced solid tumors, as part of a collaboration established with Merck KGaA and Pfizer — the two companies developing and commercializing Bavencio.
The trial is expected to begin recruiting 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,” Cynthia Sirard, MD, vice president, Clinical Development of Leap Therapeutics, said in a press release.
TRX518 is part of a new class of therapies, called immune checkpoint agonists, that amplify the immune system’s response to cancer. The molecule is an antibody that binds the GITR receptor, but unlike other antibodies, which inhibit signaling, TRX518 is made to activate this receptor.
Activation of GITR increases the production of pro-inflammatory molecules, reduces immunosuppression, and increases anti-cancer responses overall.
This is thought to work well in combination with other cancer therapies, such as immune checkpoint inhibitors — like Bavencio — and cancer vaccines.
And indeed, preclinical studies in mice with colorectal cancer have shown a synergy between TRX518, an immune checkpoint inhibitor against the CTLA-4 molecule, and chemotherapy.
TRX518 is currently being studied two Phase 1 studies (NCT01239134 and NCT02628574) in multiple advanced solid tumor types. Results to date have shown durable disease stabilizations, with clear signs of immune activation.
“TRX518 has demonstrated encouraging potential with early clinical activity in patients with advanced solid tumors,” Chris Boshoff, MD, PhD, senior vice president and head of immuno-oncology, early development and translational oncology at Pfizer Global Product Development, said in a press release. “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,” Boshoff said.
Bavencio is approved for metastatic Merkel cell carcinoma and previously treated advanced or metastatic urothelial carcinoma. The molecule binds to the PD-L1 protein in cancer cells, blocking the “don’t kill me” sign sent to immune cells.
“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, which in the U.S. 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.”
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