“We are pleased with the clinical progress
Study Design and Findings for MK-5890 (Database cutoff date:
In this Phase 1, open-label, multi-arm, multicenter, dose-escalation clinical trial (see www.clinicaltrials.gov, identifier NCT03396445), MK-5890 was administered to patients with advanced solid tumors by intravenous (IV) infusion every three weeks. Dose escalations for MK-5890 were 2 – 700 mg and pembrolizumab was administered as an IV injection at a dose of 200 mg every three weeks. Patients receiving MK-5890 as monotherapy who progressed while on therapy were eligible for crossover to the MK-5890-pembrolizumab combination arm. Study objectives included evaluation of safety, tolerability, pharmacodynamics, pharmacokinetics and tumor responses evaluated using RECIST v1.1 criteria.
Interim data presented at
In the initial phase, dose-limiting toxicities, all of which were associated with infusion-related adverse events, were reported in 12 percent (n=3/25) and 5.3 percent (n=1/19) of patients in monotherapy and combination arms, respectively. Maximum tolerated dose was defined as 200 mg every three weeks. Treatment with MK-5890, alone and in combination with pembrolizumab, demonstrated an acceptable safety profile. Grade 3 – 4 treatment-related adverse events (TRAEs) were reported in 24 percent (n=6/25) and 21.2 percent (n=4/19) of patients in monotherapy and combination arms, respectively. The most common TRAEs (occurring in ≥10% of patients) in both study arms included: fatigue, infusion-related reaction, nausea, pruritus, rash, myalgia and vomiting. In the combination arm, additional TRAEs occurring in ≥10% of patients included: chills, diarrhea, pyrexia, dry mouth, influenza-like illness and increased amylase.
About CD27 and MK-5890
CD27 signaling plays a role in cytotoxic T lymphocyte responses and the survival of activated T cells. CD27 triggering enhances the priming of cytotoxic T lymphocyte responses, thereby suggesting anti-CD27 is a promising immunotherapeutic approach for treatment of cancers. MK-5890 is a humanized agonist monoclonal antibody that binds to CD27 to provide a costimulatory signal that enhances T-cell-mediated responses. Preclinical data from syngeneic tumor studies with a human CD27 knock-in mouse model have demonstrated efficacy of MK-5890 as both monotherapy and in combination with anti-PD-1. MK-5890 is currently being evaluated in a Phase 1 clinical trial for the treatment of advanced solid tumors (see www.clinicaltrials.gov, identifier NCT03396445).
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding our intentions or current expectations concerning, among other things, the potential for MK-5890, an anti-CD27 agonist alone or in combination, the potential for our other therapies, our eligibility to receive additional milestone payments or royalties for MK-5890, Merck’s further exploration of MK-5890’s potential in expansion cohorts, including an arm of MK-5890 administered with pembrolizmab, pemetrexed and carboplatin in patients with non-squamous non-small cell lung cancer, the further progress of our and Merck’s clinical programs and our ability to expand and drive our product pipeline alone or with collaborators. In some cases, you can identify these statements by forward-looking words such as “may,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect” or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, early or preliminary clinical trial results may not be predictive of future results, our history of net operating losses and uncertainty regarding our ability to achieve profitability, our ability to develop and commercialize our product candidates, our ability to use and expand our technologies to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, our reliance on third parties, and our ability to obtain and adequately protect intellectual property rights for our product candidates. We discuss many of these risks in greater detail under the heading “Risk Factors” contained in our quarterly report on Form 10-Q for the quarter ended
Source: Aduro Biotech, Inc.