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Combining Keytruda, Imprime PGG Nearly Doubles Survival Rate for TNBC Patients Compared to Keytruda Alone

NEW YORK – The combination of anti-PD-1 immunotherapy pembrolizumab (Merck's Keytruda) with Imprime PGG, a dectin receptor agonist being developed by Biothera Pharmaceuticals, nearly doubled the median overall survival rate for metastatic triple-negative breast cancer (mTNBC) patients in a Phase II clinical trial of the combination compared to pembrolizumab monotherapy.

According to data presented at the American Association for Cancer Research's Virtual Annual Meeting this week by John Wayne Cancer Institute Executive Director Steven O'Day, mTNBC patients taking the combination regimen had an overall survival of 16.9 months compared to nine months for those taking pembrolizumab alone.

TNBC patients lack expression of HER2, estrogen receptors, and progesterone receptors. This breast cancer subgroup has the poorest prognosis and limited treatment options.

Importantly, the trial found that a subgroup of patients — those who had been estrogen receptor/progesterone receptor-positive but converted to TNBC status — responded significantly well to the combination regimen, though it is unclear what the underlying biological mechanism for this response is, as of yet. "Clearly, [this is] an interesting subgroup within this cohort that deserves further evaluation," O'Day said.

The data comes from IMPRIME 1, a single-arm Phase II clinical trial evaluating Imprime PGG and pembrolizumab in 44 chemo-refractory mTNBC patients. Imprime PGG is a novel beta glucan derived from Saccharomyces, O'Day said. It binds endogenous anti-beta glucan antibodies to form an immune complex. This immune complex becomes the active drug, binding the dectin-1 receptor and its co-receptors, reprogramming the tumor microenvironment, activating antigen-presenting cells, and increasing tumor-specific T cell activation and infiltration.

Approximately 600 patients and healthy volunteers have been treated with the compound in clinical trials to date, where it has been given as monotherapy and in combination with anti-angiogenic antibodies or tumor-targeting antibodies, with or without chemotherapy.

O'Day noted that Merck's KEYNOTE-086 trial testing pembrolizumab as a monotherapy in 170 mTNBC patients who had failed chemotherapy showed a limited benefit. The overall response rate was 5.3 percent, the six-month disease control rate was 7.6 percent, median progression-free survival was two months, and the median overall survival was nine months.

"Clearly, improvement in these low response and survival rates in triple-negative breast cancer is needed," O'Day said.

By comparison, in IMPRIME 1, for patients receiving the combination of pembrolizumab and Imprime PGG, the median overall response rate was 15.9 percent, the six-month disease control rate was 25 percent, the median progression-free survival was 2.7 months, and the median overall survival was 16.4 months.

Of special interest was the subgroup of 12 patients who were originally hormone receptor-positive and therefore, endocrine therapy responsive, but then converted to TNBC. They had previously been treated with Tam, aromatase inhibitors, or CDK4/6 inhibitors, and all had at least one line of chemotherapy in the metastatic setting. "Interestingly, these 12 patients did remarkably well, with 50 percent having an objective response rate," O'Day said. "Those 50 percent had greater than six-month disease control rate and a median overall survival of 17.1 months."

He noted that the efficacy in this group should be followed with further studies, as it's not clear whether hormone resistance or secondary triple-negative status is responsible for the more pronounced clinical benefit of the combination therapy in these patients.