Combining immunotherapy and chemotherapy for better outcomes in pediatric solid tumors
Solid tumors that recur after treatment or stop responding to chemotherapy are extremely challenging to treat. Hoping to improve outcomes for children with relapsed and refractory cancers, experts at Children’s Health℠ and UT Southwestern are leading a clinical trial of a new treatment that combines an immune checkpoint inhibitor (ICI) with chemotherapy.
Arhanti Sadanand, M.D., Pediatric Hematologist/Oncologist at Children’s Health and Assistant Professor of Pediatrics at UT Southwestern, is leading the multisite VITAS trial exploring the combination of three chemotherapy drugs – vincristine, irinotecan and temozolomide – with the ICI atezolizumab.
What the phase I study found:
A recently completed phase I study determined the approach was safe and feasible in a small cohort of children with relapsed and refractory solid tumors. Now, the researchers are recruiting patients for a phase II trial that will assess whether the combination therapy improves outcomes for children and young adults with rhabdomyosarcoma.
“Survival rates for relapsed rhabdomyosarcoma are unfortunately very poor and there is a critical need for new treatment options.” Dr. Sadanand says, “Our hope is that by combining immune checkpoint inhibition with a chemotherapy backbone, we can maximize the response to improve outcomes for children with relapsed and refractory cancers.”
Why it matters: Adding an immune checkpoint inhibitor is safe and feasible
ICIs have revolutionized the treatment of some cancers, especially in adults. Yet these immunotherapy approaches have been slower to make an impact in pediatric cancers, in part because pediatric tumors tend not to provoke a strong immune response. However, combining an ICI with an established regimen of chemotherapy drugs may make the tumors more vulnerable.
“Exposing cancer cells to chemotherapy upregulates certain proteins on the cell surface. Those proteins summon the body’s immune system to fight the cancer cells,” Dr. Sadanand explains. “The idea is that by using chemotherapy, we can make tumor cells more vulnerable to immune checkpoint inhibition."
In a first step to test that idea, the phase IVITAS trial enrolled six children from participating pediatric centers nationwide, including Children’s Medical Center Dallas. Patients received atezolizumab alongside the established chemotherapy trio of vincristine, irinotecan and temozolomide. The therapy was well tolerated by patients, who were all able to complete the planned course of treatment. “Encouragingly, we didn’t see any dose-limiting toxicities. Any adverse events were things we would expect to see with immunotherapy or chemotherapy, and they were all very manageable,” Dr. Sadanand says.
The team published the results in Pediatric Blood & Cancer.
What to know: The phase II VITAS trial is recruiting patients
The first wave of the VITAS trial focused on safety and was not designed to draw conclusions about treatment outcomes. But there were encouraging signals that patients were responding. One patient with rhabdomyosarcoma had a sustained partial response through sixteen 21-day treatment cycles. Another with pulmonary osteosarcoma had ongoing stable disease through 20 cycles.
Now the trial is continuing with a phase II cohort to answer questions about treatment efficacy. This phase of the study will enroll patients between 6 months and 30 years who have relapsed or refractory rhabdomyosarcoma. The research team opted to focus on rhabdomyosarcoma in part because these tumors are likely to express PDL-1, a cell-surface molecule targeted by atezolizumab.
What’s next: Phase II enrollment
The researchers plan to enroll 17 patients across at least seven study sites nationwide. Dr. Sadanand and her colleagues will assess objective response rates, duration of response and progression-free survival. Although rhabdomyosarcoma is one of the more common solid tumors in children, it is still a rare cancer, and the team expects it could take several years to complete enrollment, Dr. Sadanand says.
Why Children’s Health: Leaders in emerging therapies for childhood cancers
The VITAS trial is being conducted within the Developmental Therapeutics Program at Children’s Health. As one of only a few cancer programs in the country that enrolls pediatric patients in phase I and phase II clinical trials, the program offers access to promising new therapies for young patients with challenging cancers. The specialists and subspecialists in the Developmental Therapeutics Program are nationally and internationally recognized both for their innovative research and outstanding patient care.
“The Developmental Therapeutics Program primarily conducts clinical trials for patients with relapsed and refractory disease who may not have many other treatment options,” Dr. Sadanand says. “With years of experience connecting patients to these study opportunities, our specialists have the unique expertise to support patients enrolled in these trials while advancing important research on pediatric cancers.”
Read more about the Developmental Therapeutics Program or learn how to refer a patient for the VITAS study.
