Tumor-Agnostic Basket Trials Open Clinical Trial Access for Rare Cancers, Led by Larotrectinib Success in CIFS
核心洞察
Tumor-agnostic drugs and basket trials are expanding clinical trial access for people with rare cancers (搜索) who historically lacked standard treatment roadmaps and trial options.
In a basket trial spanning 17 cancer types, the NTRK (搜索) inhibitor larotrectinib shrank tumors in 75% of patients and prevented progression for at least one year in about 55%.
Larotrectinib became the second tumor-agnostic targeted therapy approved by the FDA based on basket trial results, offering children with CIFS a way to potentially avoid harsh chemotherapy and surgery.
Basket trials and tumor-agnostic therapies are reshaping how rare cancers (搜索) are studied and treated, offering patients who once faced "a world without standard treatment roadmaps, clear prognoses, or strong patient support networks" new routes into clinical research, according to experts cited by the American Cancer Society (ACS).
"Tumor-agnostic basket trials have transformed cancer care and accelerated new targeted therapies," said Alberto Pappo, MD, an American Society of Clinical Oncology (ASCO) expert and pediatric oncologist at St. Jude Children's Research Hospital. "This is great news for people with rare cancers (搜索)."
A Study Design Built Around Genetic Changes
Basket trials, also known as bucket trials, test new drugs in people whose cancers share the same genetic change, rather than grouping patients by tumor type or organ of origin. This design allows people with rare cancers (搜索) and those with more common cancers to enroll in the same clinical trial. If the treatment proves safe and effective, it can be approved to treat multiple cancers carrying that genetic alteration.
The approach addresses a long-standing obstacle in rare cancer research. In the past, few trials studied rare cancers (搜索) because not enough patients could take part, and smaller studies made it difficult to collect sufficient data on how well a treatment worked.
"Healthcare providers, patients, and families often didn't know what trials existed for rare cancers (搜索)," said Brenda J. Weigel, MD, an ASCO expert and vice president of clinical research industry engagement at St. Jude's. "Someone who wanted to join a clinical trial might have to travel long distances to places with expertise in those conditions."
Tumor-agnostic drugs complement this design by acting on specific features or genetic changes in cancer cells rather than on a single tumor site. "Clinical trials help cancer researchers develop new therapies faster," Weigel said.
Larotrectinib and the CIFS Precedent
Congenital infantile fibrosarcoma (搜索) (CIFS) illustrates the impact of the tumor-agnostic, basket-trial model. CIFS is a rare cancer affecting only about 5 in every 1 million children, yet it is the most common soft tissue sarcoma diagnosed in children under 2 years old. Traditional treatment has included surgery and, in some cases, chemotherapy — interventions that, because they occur so early in life, can cause long-term side effects.
Nearly everyone with CIFS has a change in the NTRK (搜索) gene, and several other cancers affecting children and adults carry the same alteration. Using a basket-trial design, researchers tested the NTRK inhibitor larotrectinib in children and adults whose cancers had NTRK gene changes. The study encompassed 17 different types of cancer, including CIFS.
Results showed the treatment shrank tumors in 75% of patients and prevented cancer from getting worse in about 55% of patients for at least one year. Following these studies, larotrectinib became the second tumor-agnostic targeted therapy approved by the US Food and Drug Administration (搜索) based on basket trial results. Because it targets a specific type of NTRK (搜索) genetic change, it can treat different cancers carrying that alteration, including CIFS.
Having larotrectinib available for children with certain rare cancers (搜索) may allow some to avoid harsh chemotherapy and surgery. "Getting new cancer drugs to children early, in kid-friendly forms, was critical to the success of larotrectinib," Pappo said.
Not every rare cancer has a genetic change that can be targeted with current therapies, so basket trials may not be an option for all patients. "Your cancer care team can help determine whether you're eligible to join a basket trial. If you are, they should be able to help you enroll in the study or connect you to the right people," Weigel said.
Matching Patients to Trials Through ACS ACTS
Alongside these scientific advances, ACS is working to remove practical barriers to trial participation through ACS ACTS™ (Access to Clinical Trials & Support). The program connects patients, caregivers, and providers with trained ACS cancer information specialists who help them understand how clinical trials may fit into a treatment journey and explore personalized options.
Through a simple online form, a patient, caregiver, or provider submits basic information, including the type of cancer and support needs. ACS ACTS uses artificial intelligence to analyze that information and provide a list of potential clinical trials. Throughout the process, the program offers resources and free ACS services, such as Road To Recovery® and Hope Lodge® communities, aimed at addressing barriers to enrolling and staying in a trial.
The need for such navigation is well documented. Clinical trials depend on finding eligible volunteers, but enrollment is often constrained by limited access in rural or underserved areas, hesitancy driven by mistrust in the medical community or fear of being part of an experiment, concern over possibly receiving a placebo — though most cancer trials do not use placebos unless no standard treatment exists — and simple lack of awareness that trials exist.
For providers, the screening burden is substantial. "At my cancer program, a research coordinator could spend an hour screening just one patient's chart for potential trials. It creates a real bottleneck," said Douglas Flora, MD, a medical oncologist and executive medical director of the Yung Family Cancer Center at St. Elizabeth Healthcare (搜索) in Kentucky, and an ACS regional board member for Ohio and Kentucky.
Equity Gaps Persist in Trial Enrollment
Participation in cancer clinical trials remains lowest among groups with some of the highest incidence rates. In the U.S., Black people have higher cancer incidence and death rates for several cancers compared with White people. While Black people make up about 13% of the U.S. population, only about 5% of clinical trial participants are Black. Native Americans, people living in rural areas, and older adults are also underrepresented.
"If you are Black or Hispanic or if you live in a low-resource area, the enrollment remains very low," Flora said, attributing part of the gap to the historical exploitation of Black men and women in medical research, which has fostered mistrust.
Flora's commitment to trial access is personal. His mother died of metastatic breast cancer (搜索) more than 30 years ago without being offered information about clinical trials. "My mom never had those options," he said. "In the 1990s, access to clinical trials in community settings was limited and often discouraged." Years later, when he was diagnosed with cancer himself, he was not eligible for available trials. "We didn't have clinical trials available for my cancer stage in my community," he said.
ACS hopes ACTS can boost enrollment among underserved populations by improving education and awareness. For Flora, higher participation could accelerate the research cycle itself. "I would love to accelerate the enrollments so that these trials can close sooner so that my patients can get access to those drugs sooner," he said.