Phosplatin Therapeutics releases Phase 1b results for PT-112/avelumab combo

NEW YORK—Today, Phosplatin Therapeutics has released data from a Phase 1b dose escalation study of lead candidate PT-112, wherein PT-112 was used in combination with avelumab in patients with progressing solid tumors who had previously exhausted all available treatment options.

Data were pre-released under the Mini Oral presentation format in the Investigational Immunotherapy category at the European Society for Medical Oncology Virtual Congress 2020, taking place September 19-21. The presentation is available on-demand for the duration of the conference to registered attendees, and the abstract is publicly available.

Avelumab is co-developed and commercialized by Merck KGaA, Darmstadt, Germany and Pfizer Inc. This study was conducted under a collaboration agreement between Phosplatin Therapeutics, Pfizer and Merck KGaA. Under the terms of the collaboration, Phosplatin Therapeutics is sponsoring Phase 1b/2a clinical trials in several indications. Pfizer and Merck KGaA are supplying avelumab for the trials.

The combination of PT-112 and avelumab was found to be safe and well tolerated in heavily pretreated solid tumor patients who have exhausted standard therapy options, the majority of whom had received prior immunotherapy. Common treatment-related adverse events (TRAEs) were nausea (47 percent), fatigue (31 percent), thrombocytopenia (28 percent) and decreased appetite (28 percent). 44 percent of patients had grade 3-4 TRAEs and the most frequent was thrombocytopenia, at 17 percent.

The study enrolled 36 patients with progressing solid tumors across a range of tumor types, including 15 patients with metastatic castration-resistant prostate cancer (mCRPC) who were enrolled in a supplemental cohort. Phase 2 studies are planned to confirm the recommended dose, and to implement correlative immune-profiling assays.

“These results demonstrate that the PT-112 and avelumab combination is safe and well tolerated in heavily pretreated patients,” said Daniel D. Karp, M.D., professor of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center. “As in any advanced cancer population treated with numerous prior therapies, appropriate dose modifications are important. We are encouraged by activity observed thus far, and we look forward to confirming the combination dose in future studies as we seek treatment options for these patients who effectively have no other therapeutic alternatives remaining.”

Clinical benefit was observed in patients treated with PT-112 doses ranging from 150 to 360mg/m². Sixty percent of patients with RECIST-evaluable disease achieved stable disease or better — including a durable RECIST response, PSA response and improvement in bone scan and bone pain in a patient with mCRPC with eight prior therapies and no signature of likely response to immune checkpoint inhibition. Further activity signals were observed in patients with mCRPC, with 4 of 14 patients achieving a >50% PSA reduction, and consistent reduction in alkaline phosphatase levels associated with bone metastatic site of disease.

“The results of this first combination study, including the evidence of activity among patients with prostate cancer, are indeed encouraging. Based upon these data, our immunotherapy combination appears feasible and active,” added Robert Fallon, co-founder and chief executive officer of Phosplatin Therapeutics. “These results add to the emerging body of evidence around the potential of PT-112, as an immunogenic cell death inducer, to provide benefit to patients with advanced solid tumors, and to offer a potential treatment to patients who do not respond to current immunotherapy options.”

PT-112 is a small molecule conjugate of pyrophosphate that promotes immunogenic cell death, or the release of damage associated molecular patterns that lead to downstream immune effector cell recruitment in the tumor microenvironment. The drug candidate is currently under Phase 2 development.

The novelty of PT-112’s pyrophosphate moiety also results in osteotropism, or the propensity of the drug to reach the mineralized bone. This property is of interest in cancer types that originate in bone or that lead to metastatic bone involvement, such as mCRPC.