Teon Therapeutics has entered into a clinical trial collaboration with Merck to assess TT-816 and pembrolizumab in a phase 1/2 study.
Treatment with the novel agent TT-816 in combination with pembrolizumab (Keytruda) will be evaluated for the treatment of patients with advanced solid tumors, in a phase 1/2, 2-armed, open-label, dose-escalation, and dose-expansion study (NCT05525455).1
The trial will enroll patients with a variety of difficult-to-treat cancers who have not responded to the standard of care and may have limited treatment options.
“We are fortunate to have the opportunity to collaborate with Merck for this phase 1/2 trial. The collaboration of the combination arm of our TT-816 clinical trial represents an important advancement in our comprehensive development program and further supports our mission to invent new hope for patients by potentially providing meaningful treatments to those with few remaining alternatives,” said Serge Messerlian, chief executive officer of Teon Therapeutics, in the press release.
“In addition to its great potential as a monotherapy, by blocking both the PD-1 and CB2 pathways, we believe that TT-816 in combination with [pembrolizumab] may have an additive benefit in ‘hot’ tumors and synergistic effect in ‘cold’ tumors that may result in improved outcomes for more patients. Results of our preclinical studies indicate that TT-816 has unique mechanisms of action that enhance both T cell and NK cell antitumor immunity, prevent broad-based T cell exhaustion, synergize antitumor effects with current immune checkpoint inhibitor therapies, and directly promote T cell infiltration into solid tumors.”
TT-816 is a first-in-class, oral cannabinoid CB2 receptor antagonist that acts as a novel immune response modifier to treat a variety of solid tumors. The agent is highly selective for the CB2 receptor vs the CB1 receptor. TT-816 can potentially enhance T-cell and NK cell activity and directly promote T-cell infiltration into solid tumors.
In preclinical TT-816 enhanced the effect of NK cell tumor killing and T-cell activation in vitro, and increased tumor infiltrating T cells and NK cells in vivo. The agent also prevented broad-based T-cell exhaustion.
Within this first-in-human study, TT-816 will be evaluated alone and in combination with a PD-1 inhibitor in advanced cancers. In phase 1 of the trial, investigators will define the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of TT-816 as a single-agent and as a combination therapy. Phase 2 will then define these regimens' preliminary efficacy in patients with advanced solid tumors, including non–small cell lung cancer (NSCLC), ovarian cancer, and renal cell carcinoma (RCC).2
Approximately 200 patients aged 18 years and older who have a histologically or cytologically documented, locally advanced, or metastatic solid tumor, disease progression confirmed by imaging, an ECOG performance status of 0 or 1, and measurable disease as determined by RECIST v.1.1 or bone-only disease will be enrolled in the trial.
The trial will exclude patients who have a history of severe hypersensitivity to any ingredient of the study drug, impaired cardiac function, a history of clinically significant cardiac disease, human Immunodeficiency virus infection, active hepatitis B infection, or hepatitis C infection, untreated central nervous system (CNS), epidural tumor or metastasis, or brain metastasis.
Investigators are evaluating the primary end points of incidence of adverse events (AEs), dose-limiting toxicities, MTD or RP2D, and anti-tumor activity, and the secondary end points of pharmacokinetics, AEs, and progression-free survival.
Patients are currently being recruited across sites in Tennessee, Texas, and Virginia. With an estimated enrollment of 200 patients, the trial is expected to be completed on August 31, 2027.
“New treatment options are desperately needed in oncology care as today; most patients see their cancer return on current immunotherapy treatment. TT-816 in combination with [pembrolizumab] could potentially offer a clinically meaningful new option that can overcome tumor resistance mechanisms in many patients with difficult-to-treat cancers,” added Anthony W. Tolcher, MD, FRCPC, FACP, principal investigator and chief executive officer, founder of NEXT Oncology, in the press release.1