Breakthroughs

Researchers from the SU2C Pediatric Cancer Dream Team laid the groundwork for the FDA’s approval of the first CAR T-cell therapy, tisa-cel (Kymriah). Team members helped lead the first clinical trial that showed this cellular therapy—which uses patients’ own immune cells—was safe and held great promise for treating children and young adults with a very advanced form of leukemia called ALL. Kymriah is now a standard treatment for children with ALL, with some children experiencing remissions that last for several years or longer.

Research conducted by the SU2C Breast Cancer Dream Team fueled the early development of palbociclib (Ibrance), a drug that is now a standard treatment for women with the most common form of metastatic breast cancer. The team’s research showed that drugs like palbociclib that block specific proteins in cancer cells (called CDK4 and CDK6) were promising treatments for ER-positive, HER2-negative metastatic breast cancer. These studies directly led to the clinical trials that formed the basis for the FDA’s approval. Several similar drugs have since been approved, providing important new treatment options for women with metastatic breast cancer.

Research conducted by the SU2C Prostate Cancer Dream Team provided the first evidence that tumors in many men with metastatic prostate cancer have many cancer cells that struggle to repair damaged DNA. This shortcoming can make tumors susceptible to drugs called PARP inhibitors. The team’s discovery inspired the launch of the clinical trials which showed that PARP inhibitors could help men with this type of metastatic prostate cancer live substantially longer. These drugs are now standard treatments for this form of the disease.

Based in part on research conducted by SU2C-funded scientists, the targeted cancer drugs encorafenib (Braftovi) and cetuximab (Erbitux) were approved as a combination treatment of people with metastatic colorectal cancer whose tumors have a specific mutation in the BRAF gene. The combination quickly became the standard treatment for patients who have this particularly aggressive form of colorectal cancer. Researchers are now building on this treatment to develop potentially more effective treatment combinations.

SU2C-funded scientists led one of the first human clinical trials that showed the drug alpelisib (Piqray) could be an effective treatment for metastatic breast cancer. Based on later trials, alpelisib became the first-ever FDA-approved cancer drug that targets tumors with mutations in a gene called PIK3CA. Approximately 40% of women with HR-positive, HER2-negative breast cancer have tumors with these mutations. These tumors are often aggressive and don’t respond well to other standard treatments for breast cancer, making drugs like alpelisib a critically needed advance.

An SU2C Dream Team, led by Nobel Prize laureate James Allison, PhD, conducted the first clinical trials that tested combinations of immunotherapy drugs called immune checkpoint inhibitors. These initial studies opened the door for trials of immunotherapy combinations in specific cancer types. One of those trials, led by other members of the same research team, showed that these immunotherapy combinations were highly effective when given before surgery for people with early-stage lung cancer. Giving immunotherapy before surgery is now the preferred treatment for people with this less-advanced form of lung cancer.

Based on the outstanding results of a large clinical trial involving members of the SU2C Colorectal Cancer Dream Team, the FDA approved the immunotherapy drug pembrolizumab (Keytruda) as an initial treatment for people with metastatic colorectal cancer whose tumors have mutations in genes involved in the repair of damaged DNA (referred to as MSI-H or dMMR tumors). The FDA’s action made pembrolizumab the first approved immunotherapy drug for colorectal cancer. In the clinical trial, patients lived substantially longer without their cancer getting worse than patients who received the standard treatment for metastatic colorectal cancer at the time.

The SU2C Colorectal Cancer Dream Team led a clinical trial testing the immunotherapy drug dostarlimab (Jemperli) in patients with early-stage rectal cancer whose tumors have mutations in genes involved in the repair of damaged DNA (referred to as MSI-H or dMMR tumors). All 49 patients in the study had a complete response, meaning their tumors completely disappeared. The complete responses allowed patients to avoid debilitating surgeries and in most of them the cancer has not come back. Researchers are now conducting a larger clinical trial that could lead to FDA approval of dostarlimab as a presurgical treatment in people with rectal cancer, potentially changing the treatment paradigm for this cancer.

The SU2C Catalyst team led a small clinical trial that showed promising results from a cutting-edge immunotherapy treatment called TIL therapy. The findings led to the launch of a larger trial for TIL therapy in people with non-small cell lung cancer who, for different reasons, can’t receive other treatments. If similar results are seen in this larger trial, TIL therapy could become the first cellular therapy approved to treat lung cancer and offer a much-needed advance against this highly lethal disease.

The SU2C Convergence 2.0 team led a clinical trial of a personalized mRNA neoantigen vaccine to treat people with pancreatic cancer. In a small clinical trial, the vaccine—when combined with an immunotherapy drug and chemotherapy—was safe and helped some patients kickstart a strong immune response against their tumors. More recently, the researchers reported that six of the eight patients who had an immune response to the vaccine are still alive without their cancer returning, several as long as six years. The treatment is now being tested in a larger clinical trial.

A clinical trial conducted by an SU2C Catalyst Team showed that adding immunotherapy to radiation was an effective new treatment option for people with the most common forms of sarcoma—a cancer for which there have been no advances in decades. Two years after completing treatment, 70% of trial participants who received pembrolizumab as part of their treatment were alive without their cancer coming back, compared with just over half of those who received the standard treatment. Based on these unprecedented results, the combination of pembrolizumab and radiation is now the recommended initial treatment for people with these sarcomas.