On February 16, 2023 Promontory Therapeutics Inc., a clinical stage pharmaceutical company advancing small molecule immunotherapies in oncology, reported its Phase 2 clinical trial in progress of lead therapeutic candidate, PT-112, in patients with late-stage metastatic castration-resistant prostate cancer (mCRPC) (Press release, Promontory Therapeutics, FEB 16, 2023, View Source [SID1234627342]). The poster presentation took place at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers (ASCO GU) Symposium, in San Francisco.
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The poster titled, "A Phase 2 study of immunogenic cell death inducer PT-112 in metastatic castration-resistant prostate cancer patients" was presented by Alan H. Bryce, MD, Associate Professor of Medicine and Chair, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic Arizona. The goal of the ongoing study is to determine the optimal dosing level and schedule of PT-112, in line with the U.S. Food and Drug Administration’s Project Optimus. Additionally, this study is also assessing the safety and efficacy of PT-112 as per PCWG3 guidelines, as well as circulating tumor cell responses related to clinical benefit. Additional correlative research includes blood-based T cell receptor sequencing used to elucidate the underlying immune mechanism of PT-112 in humans.
"Prior clinical and non-clinical evidence provides strong rationale to further explore PT-112 as a treatment for patients with late-stage metastatic castration resistant prostate cancer, due to its immunogenicity and osteotropism," said Promontory Therapeutics co-founder and Chief Operating Officer Matthew Price. "What we believe makes this trial particularly informative is the incorporation of extensive biomarker and correlative research programs which we anticipate will provide supportive evidence of PT-112’s mechanism and help us understand patient populations for future studies."
Eligible patients must have received at least three intended life-prolonging therapies, including at least one AR-targeted therapy and at least one, but no more than two, prior lines of taxane. Patients must also have confirmed radiographic progression upon entering the trial. As of February 1, 2023, 41 patients have been treated in the study, with one of the three dosing schedules: 360 mg/m2 on days 1 and 15 of each cycle, 250 mg/m2 on day 1 and 15 of each cycle, or 360 mg/m2 on days 1 and 15 of cycle one and 250 mg/m2 on day 15 of each subsequent cycle.
"Patients with late-stage mCRPC currently have very limited treatment options that are both effective and durable," said Promontory Therapeutics Chief Medical Officer Johan Baeck, MD. "Although many trials are being conducted in prostate cancer, there are few agents with new mechanisms of action similar to PT-112. Pre-clinical research suggests that that PT-112 induces immunogenic cell death and osteotropism, and our prior dose escalation trials showed preliminary evidence of the safety, efficacy, and clinical benefit of PT-112 in mCRPC patients. We are looking forward to completing enrollment of this study in 2024 and sharing clinical and biomarker data upon completion of the study."
For more information about PT-112 and Promontory Therapeutics’ clinical pipeline visit www.PromontoryTx.com. Further details on the PT-112 clinical trial in prostate cancer (NCT02266745) can be found at clinicaltrials.gov.
About PT-112
PT-112 is the first small-molecule conjugate of pyrophosphate in oncology, and possesses a unique pleiotropic mechanism of action that promotes immunogenic cell death (ICD), through the release of damage associated molecular patterns (DAMPs) that bind to dendritic cells and lead to downstream immune effector cell recruitment in the tumor microenvironment. PT-112 represents a highly potent inducer of this immunological form of cancer cell death. Further, PT-112 harbors a property known as osteotropism, or the propensity of the drug to reach its highest concentrations in certain areas of the bone, making it a candidate for treatment of patients with cancers that originate in, or metastasize to, the bone. The first in-human study of PT-112 demonstrated an attractive safety profile and evidence of long-lasting responses among heavily pre-treated patients and won "Best Poster" within the Developmental Therapeutics category at the ESMO (Free ESMO Whitepaper) 2018 Annual Congress. The combination Phase 1b dose escalation study of PT-112 with PD-L1 checkpoint inhibitor avelumab in solid tumors was reported in an oral presentation at the ESMO (Free ESMO Whitepaper) 2020 Virtual Congress and the Phase 2a dose confirmation cohort in non-small cell lung cancer (NSCLC) patients was reported at ESMO (Free ESMO Whitepaper) I-O 2022. The Phase 1 study in patients with relapsed or refractory multiple myeloma presented at ASH (Free ASH Whitepaper) 2020 is the third completed Phase 1 study of PT-112. Monotherapy Phase 2 development is ongoing in mCRPC, and includes the Phase 2 proof of concept study in thymic epithelial tumors under the company’s formal CRADA with the NCI.