Trovagene, Inc., a clinical-stage oncology therapeutics company, taking a precision medicine approach to develop drugs that target cell division (mitosis) for the treatment of leukemias, lymphomas and solid tumor cancers, announced today that Trovagene and Nektar have entered into a research collaboration to explore the combination of Trovagene’s PLK1 inhibitor, onvansertib, and Nektar’s topoisomerase I inhibitor, ONZEALD, for the treatment of metastatic colorectal cancer (mCRC). Under the collaboration, the two companies will evaluate the antitumor activity and tolerability of the combination of onvansertib and ONZEALD in two (HT29 – BRAF mutant and HCT-116 – KRAS mutant) preclinical tumor models of colorectal cancer.
ONZEALD is the first long-acting topoisomerase I-inhibitor (Topo I) designed to enhance the anti-cancer effects of topo I-inhibition while minimizing its toxicities. In a wide range of human xenograft tumors, including two colorectal models (HT29 and DLD-1), ONZEALD has shown superior antitumor activity, compared with irinotecan.1 ONZEALD is currently being evaluated in a Phase 3 study in patients with breast cancer who have stable brain metastases.
Onvansertib, an oral and highly-selective Polo-like Kinase 1 (PLK1) inhibitor, has shown strong antitumor activity in preclinical models of colorectal cancers, and demonstrated significant and durable synergistic antitumor activity in combination with irinotecan, and was greater than either drug alone. Trovagene has three active clinical trials: a Phase 1b/2 study in relapsed or refractory Acute Myeloid Leukemia (AML), a Phase 2 study in metastatic Castration-Resistant Prostate Cancer (mCRPC) and a Phase 1b/2 study in mCRC.
“We look forward to collaborating with Trovagene to explore a combination therapy with our respective drug candidates, ONZEALD and onvansertib, in tumor models of colorectal cancer,” said Jonathan Zalevsky, PhD, Chief Scientific Officer of Nektar Therapeutics. “Importantly, this research collaboration will allow us to evaluate the efficacy of the combination in preclinical models, and potentially identify a promising treatment regimen that we would consider advancing into clinical studies.”
“Our research partnership with Nektar is a key milestone achievement in the advancement of our onvansertib clinical development program,” said Mark Erlander, PhD, Chief Scientific Officer of Trovagene. “We believe that the clinical data generated to date for ONZEALD, will potentially lead to an optimal treatment option, when combined with onvansertib, for patients with mCRC. Working together with Nektar will enable us to very quickly assess the potential value of the onvansertib/ONZEALD combination and our collective goal of developing an innovative and targeted treatment regimen that may have application in other cancer types beyond CRC.”