On December 8, 2022 Promontory Therapeutics Inc., a clinical stage pharmaceutical company advancing small molecule immunotherapies in oncology, reported Phase 2a clinical safety and efficacy data on lead therapeutic candidate PT-112 in combination with PD-L1 inhibition, in patients with advanced non-small cell lung cancer (NSCLC) at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2022 (Press release, Promontory Therapeutics, DEC 8, 2022, View Source [SID1234624971]).

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The poster titled, "A phase 2a study of the novel immunogenic cell death (ICD) inducer PT-112 plus avelumab in advanced non-small cell lung cancer patients," demonstrated that the PT-112 and avelumab combination is well-tolerated with manageable safety profile, and showed meaningful clinical benefits in patients without known predictive markers for immunotherapy response. Based on the clinical activity observed, the study’s results support further evaluation of PT-112 combinations with immuno-oncology agents and assessment of PT-112’s immunological effects in patients.

"These data give us proof of principle for the use of immunogenic cell death inducer PT-112 in combination with immune checkpoint inhibition in NSCLC patients, and are supportive of future opportunities to bring our intended immunotherapy combinations to cancer patients," said Matthew Price, Promontory Therapeutics co-founder and Chief Operating Officer. "Along with immune correlative findings, the results are encouraging. As the field of immunogenic small molecules continues to evolve, we are pleased to continue to demonstrate the ICD effects of PT-112 in human patients. Our published clinical and non-clinical studies to date have shown the potential of this approach."

The 18 patients enrolled in the study were treated with 360 mg/m2 of PT-112 on days one, eight, and 15, and 800 mg of avelumab on days one and 15, of a 28-day cycle. Eligible patients received no more than 4 prior lines of therapy and were required to have progressive disease and to have received prior anti-PD-1/PD-L1 and platinum treatment. Findings from the study include:

Common treatment-related adverse events (TRAEs) were anemia (50%), fatigue (50%), thrombocytopenia (44%), nausea (44%) and anorexia (44%).
There were no PT-112 grade 4-5 TRAEs reported.
Of the 15 patients evaluable for efficacy, six patients (40%) had stable disease or better by iRECIST criteria.
Two cases of radiographic and clinical improvement were noted:
One patient achieved unconfirmed partial response at the first imaging follow-up, with documentation of a 70% decrease in target lesions, followed by a complete response in target and non-target lesions along with relief of pulmonary symptoms. Post-progression, PET images showed that the patient’s disease remained well-controlled for an additional ~7 months with no subsequent treatments, suggestive of extended immune-related clinical benefit.
One patient achieved a metabolic FDG-PET response, showed increased T-cell fraction on treatment, and remained stable with a progression-free survival of 7.3 months.
Based on preclinical models, PT-112 is an immunogenic small molecule that induces ICD, recruits immune effector cells in the tumor microenvironment, and synergizes with immune checkpoint inhibitors.

For more information about PT-112 and Promontory Therapeutics’ clinical pipeline visit www.PromontoryTx.com.

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 reported at ESMO (Free ESMO Whitepaper) IO 2022. The Phase 1 study in patients with relapsed or refractory multiple myeloma presented at ASH (Free ASH Whitepaper) is the third completed Phase 1 study of PT-112. Monotherapy Phase 2 development is ongoing in mCRPC, and now includes the Phase 2 proof of concept study in thymic epithelial tumors under the company’s formal collaboration with the NCI.