Promontory Therapeutics Inc. has successfully completed enrollment for its Phase 2 clinical trial evaluating PT-112 in patients with late-line metastatic castration-resistant prostate cancer (mCRPC). The study reached its target enrollment of 109 patients across 32 clinical sites in the United States and France.
The open-label dose optimization and proof of concept study is investigating PT-112 as a monotherapy in a particularly challenging patient population. Enrolled patients have received at least three prior life-prolonging therapies for mCRPC and showed radiographic evidence of disease progression at study entry. The trial also includes patients with bone-only metastatic disease, creating a representative treatment population that has progressed through standard care regimens including androgen receptor signaling inhibitors, taxane chemotherapies, and other FDA-approved therapies.
"This clinical trial is the largest study to date of PT-112 and will establish the optimal dose in line with the FDA's Project Optimus, as well as proof of concept in our late-line mCRPC patient population," said Johan Baeck, MD, Chief Medical Officer at Promontory Therapeutics. "Data from our earlier Phase 1/2 studies have shown that PT-112 is clinically safe and active, and promotes immunogenic cancer cell death induced by the inhibition of ribosomal biogenesis."
This mechanism of action is particularly promising for prostate cancer, which Dr. Baeck described as an "immune-cold" disease with no broadly approved and effective immunotherapy options currently available.
Novel Mechanism of Action
PT-112 represents a significant innovation as the first small-molecule conjugate of pyrophosphate in clinical development for oncology. The compound works by inhibiting ribosomal biogenesis, which triggers immunogenic cell death through the release of damage-associated molecular patterns. These patterns bind to dendritic cells and lead to downstream immune effector cell recruitment in the tumor microenvironment.
Another notable property of PT-112 is its osteotropism—the tendency to reach its highest concentrations in certain areas of bone. This characteristic makes it particularly suitable for treating cancers that originate in or metastasize to bone, such as prostate cancer.
Previous clinical studies of PT-112 have demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients, with data published in eClinicalMedicine, part of The Lancet.
Regulatory Strategy and Data Collection
Promontory Therapeutics has outlined a clear regulatory pathway for PT-112. The company plans to hold a Type C meeting with the FDA in the second half of 2024, followed by an End-of-Phase 2 meeting. The company will also engage with European regulatory authorities.
Beyond safety and efficacy assessments, the study aims to generate supportive data through correlative research. This includes evaluating immune activation by PT-112 monotherapy through the propagation of new T cell populations, as well as measuring reductions in circulating tumor cells and circulating tumor DNA (ctDNA).
"We are confident in PT-112's potential as an effective treatment for patients with mCRPC who have progressed on androgen receptor directed therapy, chemotherapy or radioligand therapy and who lack any effective immunotherapy," said Robert Fallon, Chief Executive Officer at Promontory Therapeutics. "We look forward to presenting topline safety, efficacy, and correlative data at relevant research and medical conferences later this year."
Broader Development Program
PT-112 is currently being evaluated in multiple clinical settings. In addition to the mCRPC trial, Promontory Therapeutics is conducting a Phase 2 proof of concept study in thymic epithelial tumors under a formal Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI). For this rare cancer indication, which has no FDA-approved treatments, PT-112 has received Orphan Drug designation.
The company has completed three Phase 1 studies of PT-112, including a combination study with the PD-L1 inhibitor avelumab in solid tumors and a study in patients with relapsed or refractory multiple myeloma. Results from these studies have demonstrated both single-agent and combination anti-cancer activity.
Promontory Therapeutics, a privately held clinical-stage pharmaceutical company based in New York City, focuses on small molecule immunotherapy approaches in oncology. The company is a member of the Paris-Saclay Cancer Cluster, Europe's emerging bio-cluster for oncology, and was nominated for Best Startup by the Prix Galien USA in 2023.
With the completion of enrollment in this pivotal Phase 2 trial, PT-112 moves closer to potentially offering a new treatment option for patients with late-stage metastatic prostate cancer who have exhausted current standard therapies.
