G100 alerts the immune system to MCC tumors
When Bhatia initiated the small pilot study, it was one of the first to test any kind of immunotherapy against MCC, and the first to try injecting this particular immune-stimulating molecule directly into tumors. His team included University of Washington and SCCA colleagues Drs. David Byrd, Paul Nghiem and Upendra Parvathaneni.
The researchers recruited two groups of participants: three patients with early-stage, potentially curable MCC, and seven patients with metastatic disease whose cancer had progressed after standard treatment.
For the early-stage patients, Bhatia hoped that G100 would help standard treatment — surgery followed by radiation — work better by shrinking their tumor and making it easier to remove. The three patients with early-stage MCC were given two injections of G100 into their tumors one week apart, followed by standard radiation and surgery about three weeks after the first treatment.
The seven patients with advanced MCC were given three doses of G100 every two weeks. Some patients, including Glusman, also received further doses of G100 combined with a single dose of radiation to their tumor.
All three early-stage patients successfully completed the study with minimal side effects. More than three-and-a-half years after treatment, two of them have had no disease recurrence. All signs of tumor were eradicated in one participant after he’d received only G100.
“These are patients whose cancer could have been cured [with standard treatment] so it’s hard to know just how much G100 treatment contributed, but just the fact that treatment [with only two injections of G100 alone] led to complete eradication of cancer [in one patient] … was quite remarkable,” Bhatia said.
In contrast with chemo’s short-lived effects on this cancer, two of the patients with advanced MCC had notable outcomes after getting the G100. Glusman, who regularly commuted from his law practice in Berkeley, California, to Seattle for treatment, saw his tumor shrink beyond detection. His cancer has remained in remission for more than three years.
Tim Crichfield is another patient with metastatic disease who saw his tumor growth halt while on the study. He had been stunned to discover that what he thought was a benign cyst was actually an aggressive, advanced tumor. Crichfield commuted from New York City for treatment in late 2015 to receive three rounds of G100 injections, followed by another round and a dose of radiation.
“I had some reaction [at the injection site],” Crichfield recalled. “But Dr. Bhatia explained that it was actually a good thing.” It was probably a sign, Bhatia explained, that his immune system was answering the call and beginning to fight the tumors. Now, three years later, Crichfield gets yearly checkups and his cancer has not recurred.
Like Crichfield, several other patients experienced local and mild symptoms after G100 injection. No patients experienced body-wide toxic side effects, demonstrating the compound’s safety.
Bhatia and his team looked to see if they could detect a difference in the anti-tumor immune response after G100 injection. In several patients, they saw the number of immune cells within the tumor increase. They were also able to track these anti-tumor immune cells to other areas of the body, suggesting that G100 might be able to trigger an anti-tumor response that could target other tumors. However, due to the small number of patients in the pilot study, they were unable to correlate specific immune characteristics with clinical outcome.
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In the few years since Bhatia started the trial, the landscape of MCC treatments has changed dramatically. Bhatia was part of the team, led by Nghiem, that ran two clinical trials of a different type of immunotherapy, the checkpoint inhibitors avelumab and pembrolizumab, that led to their use as the new standard of care for patients with advanced MCC. Checkpoint inhibitors work by removing, or inhibiting, the molecular blocks that tumors use to check immune attack.
Bhatia doesn’t expect G100 to replace checkpoint inhibitors, but the approach does offer several advantages.
“It’s a personalized therapy, using each patient’s unique tumor-antigen portfolio to elicit an immune response against those tumor antigens,” Bhatia said. “Second, local administration is associated with little systemic toxicity, so it can be combined with systemic therapies.”
G100 is already being tested against other cancers, including sarcoma and melanoma. Because of its ability to overcome the immunosuppressive environment of tumors, Bhatia expects that G100 or similar compounds will work synergistically with checkpoint inhibitors, perhaps increasing the number of patients whose cancers respond to immunotherapy. Several clinical trials are already underway testing such compounds in combination with immune checkpoint inhibitors.
Though the small nature of the study makes it difficult to know for sure how G100 contributed to each patient’s results, Glusman is grateful for his rare extra years. He well remembers a dark Thanksgiving, during his early days on the trial, when the treatment made him too sick to attend a planned celebratory potluck. Instead, he stayed home and ate potluck green beans with his wife. But soon after, his tumor began shrinking. Now he regularly crosses the country to spend time with his grandchildren.
“They were both born after my diagnosis. How great is that?” he said.
The Washington state Life Sciences Discovery Fund, the National Institutes of Health, the National Cancer Institute and Immune Design funded the study.