New Options for Adolescent and Young Adult Patients with Sarcoma 

Sarcomas are cancers that occur in bone or soft tissue, such as muscles and fat. These cancers are rare and diverse, with more than 150 different variations. 

Treatment is advancing for some sarcomas, but most forms of the disease are still treated using chemotherapy, radiation and/or surgery. In some cases, there are few options if the cancer comes back. 

Dana-Farber physician-scientists are evaluating innovative new therapies in clinical trials to determine if they can benefit patients with sarcomas. One challenge, however, is that some sarcomas are more likely to occur in adolescents and young adults.  

This age group sits in a gray area between pediatric and adult oncology. Historically, few people in this age group enter clinical trials of new treatments for sarcoma. 

Dana-Farber, however, houses adult and pediatric oncology in the same building. It also has formed an Adolescent and Young Adult Sarcoma program that focuses on treating adolescent and young adult patients and developing new drugs for them. 

“We are uniquely positioned at Dana-Farber to run coordinated clinical trials across the age range from pediatrics through adulthood in sarcoma,” says pediatric oncologist David Shulman, MD, who leads the Adolescent and Young Adult Sarcoma Program at Dana-Farber. “We’ve demonstrated that we can successfully run trials for adolescents and young adults with sarcomas and we are excited to have a growing portfolio of drugs and clinical trials for these diseases.” 

Radioligand therapy for adolescent and young adult osteosarcoma 

Osteosarcoma is the most common bone tumor seen in children and young adults, with patients commonly diagnosed in their late teens. Treatments include intensive, multi-agent chemotherapy and surgery. However, for many patients, the tumors recur.  

“Treatments really have not evolved for this disease since the 1980s,” says Shulman.  

But now, radioligand therapy (RLT), also sometimes called radiopharmaceutical therapy, is being evaluated in a clinical trial for relapsed patients ages 12 and above. Shulman is one of the lead investigators on a multicenter industry-sponsored trial. The therapy targets a marker on many sarcomas called LRRC15 and delivers radioactive particles into cancer cells that contain this marker. The treatment requires close collaboration between physicians across Dana-Farber, including experts in sarcoma and nuclear medicine.  

Dana-Farber is a Comprehensive Radiopharmaceutical Therapy Center of Excellence. The team administers approved therapies and supports clinical trials of radioligand therapies.  

“At Dana-Farber, we have highly trained staff to make sure that the radioactivity and these agents are given appropriately to patients and are administered in a safe manner,” says Heather Jacene, MD, clinical director of Nuclear Medicine in the Department of Imaging.   

CAR T-cell therapy for adolescent and young adult sarcomas 

CAR T-cell therapy has revolutionized the way certain blood cancers are treated, delivering lasting remissions and, in some cases, cures. Robbie Majzner, MD, a pediatric oncologist and researcher at Dana-Farber, is designing novel CAR T-cell therapies specifically for pediatric, adolescent, and young adult patients with cancer, including sarcomas. 

A cell-surface marker called B7H3 known to be present on many pediatric solid tumors also occurs in several sarcomas. Antibody-drug conjugate (ADC) drugs that target B7H3 have been evaluated in clinical trials, and now, Majzner plans to evaluate B7H3-targeting CAR T-cell therapy for adolescent and young adult patients with sarcomas.  

“B7H3 is broadly expressed across sarcomas and at very high levels, making this an attractive target for B7H3 CAR T-cell therapy,” says Majzner.  

An advantage of CAR T cell therapy is that the T cells, which have been trained to recognize and fight cancer cells, can live for a long time in a patient after treatment, enhancing the benefit, though the actual benefit must be evaluated in clinical trials. 

Novel STEAP1-targeted therapy for adolescent and young adult Ewing sarcoma 

Another form of sarcoma, Ewing sarcoma, arises in bones or soft tissues and most commonly occurs in adolescents and young adults. Most patients who relapse after initial treatment tend to do so within two years. Patients who experience a relapse have limited options.  

Approximately 90% of Ewing sarcoma tumors express a marker called STEAP1. Recently, agents that target STEAP1 have shown activity in adult prostate cancer. These results caught the eye of Steven DuBois, MD, MS, director of Experimental Therapeutics in the Department of Pediatric Oncology. DuBois is now evaluating a STEAP1-targeting bispecific antibody in adolescent and young adult patients with relapsed Ewing sarcoma who are age 12 and up.  

“Because of the structure of our program, we’re able to deliver a clinical trial across that age spectrum,” says Dubois. 

“Another Dana-Farber benefit is the cross-pollination of ideas across the entire spectrum of cancer care,” adds Suzanne George, MD, chief of the Division of Sarcoma at Dana-Farber. “We have connections between pediatric oncology and adult oncology across the whole spectrum of diseases.” 

Bispecific T-cell engagers work by binding with both immune cells called T cells and cancer cells, bringing them closer together so that the immune system can work against the cancer.  

“Some of the side effects of bispecific T-Cell engagers can be similar to those of other cellular therapies,” says DuBois. “Dana-Farber/Boston Children’s and Dana-Farber medical oncology have expertise in managing those side effects, making this an excellent place for patients to receive these innovative therapies.” 

Innovative Degrader for adolescent and young adult Ewing sarcoma 

Ewing sarcoma is driven by a fusion protein, two proteins that bind together when they shouldn’t. Ewing sarcoma cells seem to be dependent on protein called RBM39 which is a protein involved in regulation of some cancer cells. This protein is difficult to block using traditional small molecule medicines, but a new approach employs targeted protein degradation to eliminate RBM39 from the cell and aims to control cancer cell growth. 

At Dana-Farber, a phase 1 clinical trial of an RBM39 degrader aims to determine if this drug, currently code-named ST-01156, is safe and shows activity against Ewing sarcoma and a range of other solid tumors that are locally advanced or metastatic. The degrader has shown significant activity against pre-clinical models of Ewing sarcoma. 

The trial is currently open for patients who are over 18. 

“ST-01156 aims to degrade RBM39 and therefore interfere with cellular function in Ewing sarcoma,” says George, who is leading the study at Dana-Farber. “We’re excited to learn more about this promising approach in Ewing and other sarcomas.”