U.S. regulators have cleared the way for Aduro Biotech to begin a Phase 1b clinical trial of a combination of ADU-S100 and Novartis’ PDR001 for treating lymphomas and advanced solid tumors or those that have spread.
The green light was the U.S. Food and Drug Administration’s approval of Aduro’s investigational new drug application for ADU-S100 (MIW815) plus PDR001.
ADU-S100 activates the STING immune-system pathway in a way that could help the body fight cancer. STING triggers the production of type 1 interferon to fight bacteria, viruses and other invaders. Its full scientific name is stimulator of interferon genes protein.
PDR001 is a humanized monoclonal antibody that fights programmed death-1 protein, also known as PD-1 protein. It breaks shackles that tumor cells impose on the immune system.
Aduro is evaluating ADU-S100 in a multicenter, ongoing, dose-escalation Phase 1 trial (NCT02675439) in patients with lymphomas or solid tumors that may have spread to the skin. The trial is assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of ADU-S100. Pharmacokinetics deals with the body’s impact on a treatment, while pharmacodynamics deals with the treatment’s impact on the body.
Initial results of the Phase 1 trial, coupled with results from preclinical-trial studies, indicate that a combination of ADU-S100 and an immune checkpoint inhibitor could be effective against cancer.
These results underscore “the importance of evaluating these two novel approaches to treating cancer in combination with one another,” Dr. Natalie Sacks, Aduro’s chief medical officer, said in a press release. “We look forward to initiating a Phase 1b trial in the second half of the year to gain clinical insights into the STING/anti-PD-1 inhibitor combination for the treatment of multiple tumor types. At the same time, we will continue to evaluate the potential of ADU-S100 as a monotherapy in cutaneously accessible tumors as well as viscerally accessible tumors.”
The open-label Phase 1b trial (NCT03172936) will evaluate the safety and effectiveness of ADU-S100 in up to 175 patients with lymphoma or advances solid tumors.
ADU-S100 will be administered directly to a tumor. PDR001 will be administered intravenously.
The trial’s primary objective is to determine the combo’s dose-limiting toxicity. The research team defines that as the dose that triggers an adverse event or leads to laboratory signs of toxicity.
One of the trial’s secondary objectives is an assessment of lab signs of the drug’s behavior in the tumor and in blood. Another secondary measure will be the treatment’s impact after 36 months. Components of that measure will be the time it takes patients to respond to the combo; overall response, or the number of patients who respond either fully or partially; progression-free survival, or how long it takes for patients’ disease to progress after treatment; and the disease control rate, or the percentage of patients who receive some benefit from treatment.