A clinical trial investigating a promising blood cancer therapy treated its first patient in August 2024 after receiving fast-track activation from the Stanford Cancer Institute in March 2024. The study is led by Jason Gotlib, MD, MS, leader of the Stanford Cancer Institute Hematology Clinical Research Group.
Gotlib says, “This is practice-changing research led by the Stanford Hematology Clinical Research Group that has led to four FDA drug approvals for patients with myeloproliferative neoplasms, a group of blood cancers that occur when the bone marrow produces too many blood cells.”
The therapy treats a form of blood cancer called myelofibrosis, which is characterized by progressive scar tissue accumulation in the bone marrow, lower blood cell counts, the potential to develop leukemia, and early death. Splenomegaly, also known as an enlarged spleen, is a cardinal feature of the disease, which can lead to abdominal pain and marked weight loss.
The disease is driven by several acquired mutations that cause unregulated production of abnormal blood cells. The most notable of these mutations is JAK2 V617F, a mutation of the JAK2 gene. Four drugs that inhibit JAK2 and JAK-STAT signaling have been approved to treat myelofibrosis. While these drugs can reduce splenomegaly and improve symptoms, unfortunately, they don’t typically modify the potential for disease progression and can have significant side effects.
Gotlib says, “These drugs are not specific for the mutant JAK2 protein but also target normal JAK2, which is important for the production of normal blood cells. This explains why the currently approved JAK inhibitors often cause anemia and other hematologic toxicities, a major challenge in these myelofibrosis patients who already suffer from low blood counts.”
The fast-track clinical trial is a phase I, first-in-human study evaluating a drug called INCB160058. This drug inhibits only the JAK2 V617F mutation without targeting the normal JAK2 gene. The study protocol initially evaluates drug tolerability and safety to identify the highest dose patients can tolerate without severe side effects. Once the right dose is identified, the study investigators hope that INCB160058 will be more effective and safe compared to the currently available JAK inhibitors used to treat myelofibrosis.
Gotlib ultimately hopes that this second generation of more highly targeted drugs, such as INCB160058, can be paired in future clinical trials with drugs that have different mechanisms to improve the survival of patients with these rare, poor-risk hematologic malignancies.
Stanford has treated four patients on the protocol and several more individuals have been identified for screening. Additional study sites have recently opened in the United States. The study is being conducted with the study sponsor Incyte Corporation, manufacturer of INCB160058.
Stanford Cancer Institute fast-track activation
The group submitted the study for Stanford Cancer Institute fast-track activation, which speeds up study activation from around six months to under 90 days. Gotlib’s study was selected on March 3, 2024 and activated in 74 days.
The study met all four of the criteria to quality for fast-track activation, though only one needs to be met for consideration:
High-accruing study, with the study aiming to enroll 12 patients in the first year of activation
First in human with Stanford being the first to open
The Stanford principal investigator is the global principal investigator (PI), meaning they are the PI for all sites, with guaranteed authorship
Opportunity to enroll minority patient population where fast activation will be critical
Agnes Nika, director of Stanford Cancer Institute Clinical Trials Office Research Services, oversees the fast-track program, which launched in February 2024. She says the program addresses the need to shorten study activation time so patients have access to innovative treatments sooner. Five studies have received fast-track activation service.
Nika says a committee oversees the application process and chooses studies that promise to have a significant impact on patient care and enroll many patients, and where Stanford has a leadership position. Committee members excuse themselves if there is a conflict of interest, for example, a member is part of the research group submitting the application.
The program speeds up study activation by assigning study activation specialists to collaborate with Stanford stakeholders to shorten the turnaround time around gathering and processing documents. These stakeholders include the Stanford Cancer Institute Clinical Trials Office finance and regulatory teams, Clinical Translational Research Unit, EPIC Beacon Team, Investigational Drug Service, Institutional Review Board, and Research Management Group. An activation specialist keeps track of the project dates, records, and submissions and is included on all communications to help facilitate the process.
Nika says, “I talk with all the stakeholders who are part of the activation and negotiate a quicker turnaround time, including turnaround times for questions and email communications and letting others know this is a high-profile study that needs attention. We also collect documents ahead of time, filling out many of the feasibilities even before the studies have been accepted at our intake, and we help manage some of the active project management aspects on the tail-end to speed up the close-out process, which can be delayed due to many holdovers.”
Annie Jung, cancer clinical research supervising lead for the Stanford Cancer Institute Hematology Clinical Research Group, is the liaison between Stanford and the study sponsor. She says the process was the same as non-fast-track studies but necessitated minimal waiting time from stakeholders. Justin Abuel, cancer clinical research manager for the Stanford Cancer Institute Hematology Clinical Research Group, says communication was the biggest driving force in accelerating the process.
Abuel adds, “The most rewarding part is knowing that we’re able to open up studies sooner so that we can make an impactful contribution to accruing for the study and make treatments available for patients who need it. There’s such a high mortality rate with leukemia, and if it takes forever to open studies, we lose our opportunity to provide them with those treatments. That we could open in 74 days from when we were selected was a game-changer for us.”
November 2024
Katie Shumake
