The FDA cleared an investigational new drug application for a phase 1b clinical trial examining DSP107, a first-in-class anti-CD47 fusion protein, in patients with acute myeloid leukemia and myelodysplastic syndrome.
The FDA has cleared an investigational new drug application for a phase 1b clinical trial examining DSP107, a first-in-class anti-CD47 fusion protein, in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), according to an announcement from the cancer immunotherapy company KAHR Medical.1
The phase 1b, open-label, dose-escalation study (NCT04937166) will evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of the agent as a monotherapy, as well as in combination with azacitidine or azacitidine plus venetoclax (Venclexta) in patients with AML and MDS. The trial is anticipated to begin at the end of 2021 and will be conducted at The University of Texas MD Anderson Cancer Center.
“The FDA clearance to commence our phase 1b clinical trial for DSP107 in hematological cancers is a significant milestone for KAHR as we advance into the clinic with our second clinical study for our lead program with the backing and support of the Cancer Focus Fund," Yaron Pereg, PhD, chief executive officer of KAHR, stated in a press release. "In parallel, we are making excellent progress with DSP107's dose-escalation and -expansion study as a monotherapy and in combination with atezolizumab [Tecentriq] in patients with advanced solid tumors.”
DSP107 is a CD47x41BB targeting compound that binds cancer and immune cells simultaneously, and links them together for maximum immune system activation against the cancer. The agent was developed to activate an effective, local response of innate and adaptive immunity, as well as to weaken tumor defenses.
Moreover, DSP107 is an inhibitor of CD47, an immune checkpoint protein that allows tumors to attack and evade immune recognition; CD47 is overexpressed in various cancer types. Additionally, the agent binds 41BB on T cells and stimulates their activation, which ultimately results in targeted immune activation through macrophage and T-cell–mediated tumor destruction.
“KAHR's multifunctional immuno-recruitment fusion proteins exemplify the innovative approach to cancer we seek to support,” Ross Barrett, founder and managing partner of Cancer Focus Fund, stated in a press release. “Achieving FDA clearance for the commencement of the phase 1b clinical trial showcases KAHR's ability to execute its regulatory strategy, and we look forward to the launch of the trial.”
DSP107 is also currently under investigation in a phase 1/2 trial (NCT04440735) examining the use of the agent in the treatment of patients with advanced solid tumors. The first-in-human, multicenter, open-label, dose-escalation and -expansion study is anticipated to enroll up to 115 patients and it is comprised of 2 parts.
The first portion of the research is examining the safety, pharmacokinetics and pharmacodynamics of the agent as a monotherapy and in combination with atezolizumab. The second portion of the study will evaluate the efficacy of DSP107 as a monotherapy, and in combination with atezolizumab, in patients with advanced non–small cell lung cancer who have progressed on prior treatment with a PD-1/PD-L1 inhibitor.2
To be eligible for enrollment, patients needed to have an ECOG performance status of 0 or 1 and measurable disease per RECIST v1.1 criteria. For part 1, patients needed to have a histologically confirmed solid tumor that was not amenable to surgical resection or other approved options.3 For part 2, patients needed to have histologically confirmed, inoperable NSCLC that was stage IIIB or stage IV, disease that was wild-type for oncogenic driver mutations, and they had to have received frontline treatment with a PD-1 or PD-L1 agent with or without chemotherapy and have achieved a best response of stable disease.
If patients had a life expectancy of less than 3 months, central nervous system metastases, a life-threatening immune-mediated adverse effect associated with previous immunotherapy, a past or current history of autoimmune disease or immune deficiency, or a history of autoimmune hemolytic anemia or autoimmune thrombocytopenia, a hematologic malignancy, or organ or stem cell transplantation, they were excluded.
In November 2020, the first patient was dosed on the study.
“We look forward to the topline results from the dose-escalation monotherapy part of the solid tumors study in addition to the initiation of the phase 1b clinical trial in blood cancers, both expected in the fourth quarter of this year,” Pereg added.