Blood Cancer United (formerly the Leukemia & Lymphoma Society) recently announced it had acquired the remaining supply and rights to the investigational agent luveltamab tazevibulin, an antibody drug conjugate targeting the folate receptor-1 alpha (FOLR1) molecule, from the drug’s manufacturer, Sutro Biopharma, for pediatric compassionate use. The acquisition allows the organization, in a first-of-its kind intervention, to continue compassionate use of the drug in the treatment of children with acute myeloid leukemia (AML) with the CBFA2T3-GLIS2 gene fusion. a rare and aggressive subtype of AML that affects between 4% and 15% of infants and young children with pediatric AML in the United States—about 17 children each year.1 This rare form of AML is extremely resistant to conventional chemotherapy and has a 5-year year survival rate of between 15% and 30%.2
Luveltamab tazevibulin,, which is highly overexpressed in CBF/GLIS fusion AML, was originally developed for the treatment of non-small cell lung cancer and ovarian cancer with the FOLR1 molecule. However, in 2023, data from the compassionate use of luveltamab tazevibulin in 25 pediatric patients with relapsed/refractory CBF/GLIS-positive AML presented during the American Society of Hematology Annual Meeting and Exposition demonstrated a complete remission rate of 42% in patients with significant disease and a 75% complete remission rate in those with lower disease burden.3
Despite these promising early results, in March 2025, Sutro Biopharma decided to discontinue development of luveltamab tazevibulin for its primary indication in adult cancers, subsequently ending the U.S. Food and Drug Administration’s (FDA) compassionate-use program for children. Earlier this year, Blood Cancer United acquired the pediatric rights and existing supply of luveltamab tazevibulin through its Dare to Dream Project—a $175 million campaign to accelerate treatment and care in pediatric cancers—to continue the compassionate-use program, preserving access to therapies for patients with no effective treatment options, at no cost to patients. The organization distributed the first dose of the drug to a child with AML in July.
“It is very difficult and expensive to develop new therapies for children with rare disease. Far too often, we see promising new agents become unavailable for reasons that have nothing to do with safety and efficacy,” said E. Anders Kolb, MD, President and Chief Executive Officer of Blood Cancer United. “We acquired the remaining supply of luveltamab tazevibulin to make sure children can continue to benefit for as long as the supply is available, and to highlight the simple truth that it is not okay to leave a lifesaving drug in the freezer when there is a child in need. This is not a solution to the challenges of drug development for rare indications. Rather it is an acknowledgement that we have to do better. Sutro has been a wonderful partner and did all it could, but our children need a reality that is immune to market and commercial forces.
We acquired the remaining supply of luveltamab tazevibulin to make sure children can continue to benefit for as long as the supply is available, and to highlight the simple truth that it is not okay to leave a lifesaving drug in the freezer when there is a child in need.— E. Anders Kolb, MD
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”Before joining Blood Cancer United, Dr. Kolb served as Director of the Moseley Foundation Institute for Cancer and Blood Disorders at Nemours Children’s Health; and Professor of Pediatrics at the Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia.
In this interview with The ASCO Post, Dr. Kolb discussed why Blood Cancer United took the unprecedented step of procuring a discontinued, experimental drug for pediatric patients with CBF/GLIS-positive AML; the challenges the organization faced to ensure patients would continue to receive luveltamab tazevibulin; and how this initiative can become the model for pediatric cancer drug development.
Expanding Access to an Experimental Therapy for a Rare Pediatric Cancer
Why did Blood Cancer United decide to purchase and distribute luveltamab tazevibulin to patients diagnosed with CBFA2T3-GLIS2-rearranged AML?
Interest in the study of this rare form of AML goes back 15 years. We had funded some of the early foundational research by James R. Downing, MD [President and Chief Executive Officer of St. Jude Children’s Research Hospital] that characterized this subtype of leukemia. He had served as the senior scientist in the Pediatric Cancer Genome Project and he and his colleagues discovered a specific genetic alteration that is responsible for about 30% of children ages 4 and younger diagnosed with acute megakaryoblastic leukemia (AMKL).
James R. Downing, MD
Soheil Meshinchi, MD, PhD
Dr. Downing and another researcher, Soheil Meshinchi, MD, PhD [Professor, Translational Science and Therapeutics Division at Fred Hutch Cancer Center and Professor, Division of Pediatric Hematology/Oncology at the University of Washington] recognized that very few of these patients survive this cancer. They may experience initial remission following a bone marrow transplant, but many relapse relatively quickly.
In the research that we and others have funded, Dr. Meshinchi found, through RNA sequencing and flow cytometry analysis, that this leukemia expresses folate receptor alpha (FRα), encoded by the FOLR1 gene, a key protein that binds and transports the B-vitamin folate into cells, which is rare in leukemia. We don’t see the FRα gene expressed in the normal bone marrow and we don’t see it in any other type of leukemia in children or adults, so FOLRI is a unique leukemia cell-restricted vulnerability that provides hope for an effective targeted therapy.
It is a target that is also expressed in ovarian cancer, which means that there is likely to be a commercial path for development of a targeted drug. And while there is no link between this subtype of leukemia and ovarian cancer, the finding indeed meant that we had a drug candidate available that could target CBFA2T3-GLIS2-rearranged AML. We had a relationship with the investigational agent’s drug’s manufacturer, Sutro Biopharma, through our Therapy Acceleration Program and the idea took off from there. Sutro is supportive of the compassionate use program for children, and over an 18-month period, the company had supplied luveltamab tazevibulin to nearly 50 children with this form of AML. We provided nurse navigation support for patients and their families to help with the completion of the necessary paperwork to apply for compassionate drug use, and also assisted with travel expenses to the institutions supplying the drug.
In 2023, Dr. Meshinchi and his colleagues reported on the compassionate use results related to the investigation of luveltamab as a monotherapy or in combination with a cytotoxic therapy in 25 children with relapse/refractory CBF/GLIS-positive AML. The data showed complete remission rates in 42% of the children with high disease burden and complete remission rates in 75% of the pediatric patients with lower disease burden.3
Sutro decided to end its development for luveltamab in adult patients with ovarian cancer, which meant that the pediatric compassionate use and expanded access programs ended as well. That’s when we began negotiations with Sutro to take over the supply of luveltamab and continue the compassionate use program. As an organization, we saw this as an opportunity to make sure that pediatric patients with no other treatment options would have access to a potentially very effective therapy.
Providing a Bridge to Another Therapy
How large is your supply of luveltamab tazevibulin and how many patients will be eligible to receive this treatment?
The drug has about a 2-year shelf life, but we think we may be able to extend it to buy more time. If so, our supply could last perhaps as long as 5 years. Our hope is that within that time, another drug will be developed to replace luveltamab. Our goal with luveltamab is to provide a bridge for patients, so they have options while other therapies are being investigated.
We estimate that we will be able to provide the drug to 20 patients a year in the United States.
Overcoming the Barriers to Providing Access to Investigational Drugs
Were there barriers, legal and logistic, to procuring this drug and distributing it to patients that you had to overcome?
The regulatory process that we completed to transfer the pediatric Investigational New Drug (IND) application from Sutro to Blood Cancer United, and the letter of authorization we provided to the FDA is relatively straightforward and has to be completed for each patient. Through Blood Cancer United’s clinical trials support center team who work closely with our Pediatric Acute Leukemia (PedAL) team and our clinical supply management and logistics vendors, we are committed to providing that support, so patients are able to receive luveltamab.
The real challenge for us is that we are in unchartered territory. No other nonprofit organization in the oncology space has purchased a discontinued drug candidate to distribute to patients under a compassionate use program. We have no plans to commercialize the drug. We are just trying to keep it available for as long as possible knowing that investigators are working on some exciting alternatives that may mature in the next few years. Since we are carving a new path for other entities that might want to pursue a similar program, we want to make sure we get this process right.
Nearing the Day When All Subsets of Cancer Will Be Deemed Rare Diseases
It’s unfortunate that Sutro Biopharma decided not to continue producing luveltamab tazevibulin since the drug candidate is showing such promising effectiveness in pediatric patients with CBF/GLIS-positive AML.
Yes, this is a problem we have in pediatric oncology, and a problem I’ve seen throughout my medical and academic career. It is very difficult to develop drugs for rare diseases in children. But I think it’s important to note that “rare” in diseases like cancer is the new normal.
As precision medicine becomes more refined and as our understanding of the molecular events that cause cancer becomes greater, we know that finding rare subsets of cancers will become the norm. What Blood Cancer United is doing is recognizing the fact that it’s very hard to develop drugs for rare diseases. But when we see an opportunity to do right by patients, we have to step in and do it. Accepting the shelving of potentially effective therapies for rare diseases is a reality of drug development. But when we can intervene to provide patients with possibly life-saving therapies, we have to take that step.
I also want to acknowledge that advances in science are outpacing our federal regulatory systems, and we all need to do more to help not just kids with rare diseases, but all patients.
Solving the Problem of Orphan Drug Development
Despite passage of the Orphan Drug Act to provide financial aid for research in drug development for rare cancers, research remains historically low due to small patient populations and high economic risks for pharmaceutical companies. Do you have plans to buy other discontinued drugs for compassionate use in rare blood cancers and expand your Dare to Dream Project?
We were able to procure and distribute the discontinued drug luveltamab tazevibulin to patients because it has been shown to be highly effective in this rare form of pediatric AML. But what we are doing is not scalable with other discontinued drugs. We can’t buy every shelved pharmaceutical asset.
We as a community of philanthropists and concerned investigators, federal regulators, and pharmaceutical companies need to collectively figure out how to solve the market realities that make it difficult to develop drugs for children with cancer. And there isn’t one solution. Buying discontinued, experimental drugs isn’t the solution to this problem. It’s a stopgap measure.
Building a Model for Pediatric Cancer Development
How might your initiation to buy and distribute luveltamab tazevibulin for compassionate use become a model for other nonprofits to emulate?
Acquiring supplies of promising investigational therapies that have been discontinued for compassionate use should be considered by other organizations. Pharmaceutical companies also need to be receptive to this idea. The complexity around out-licensing or providing access to an effective therapy is very challenging for drug companies because these drugs are assets. They were expensive to develop, and these companies have a fiduciary responsibility to their shareholders to maximize the value of their products. But when there is a clear benefit for a rare subset of cancer or there is a clear benefit for patients that have no other access to effective therapies for their rare disease, we have to come up with solutions to help these patients.
Blood Cancer United acquired luveltamab tazevibulin because it was the right thing to do for pediatric patients with a rare cancer that have run out of treatment options. And because we have the Dare to Dream infrastructure in place to sponsor pediatric blood cancer research and the expertise within our organization to make this challenging endeavor a reality.
We hope others will join us in this effort.
DISCLOSURE: Dr. Kolb has no financial conflicts of interest to declare.
References
1. Furlan S: Targeting the rare: A new therapy for pediatric acute myeloid leukemia with CBFA2T3-GLIS2 Fusions. The Hematologist 22(2), 2025.
2. Tang T, Le Q, Castro S, et al: Targeting FOLR1 in high-risk CBF2AT3-GLIS2 pediatric AML with STRO-002 FOLR1 antibody drug conjugate. Blood Adv 6(22):5933-5937, 2022.
3. Williams R, Miller L, Massaro S, et al: Anti-leukemic activity of luveltamab tazevibulin (LT, STRO-002), a novel folate receptor-α (FR-α)-targeting antibody drug conjugate (ADC) in relapsed/refractory CBF2AT3::GLIS2 AML. Blood 142(1):4295-4295, 2023.
