imifoplatin (PT-112) / Promontory Therap, SciClone - LARVOL DELTA

Biomarker analyses from the phase II PT-112 monotherapy study in late-line metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2025) - P2 | "The observed copy number variations were suggestive of highly aggressive, heterogenous, and multi-treatment resistant disease at study entry. Taken together, these data support PT-112 benefit in a markedly disease burdened patient population with poor survival prognosis."

Biomarker • Metastases • Monotherapy • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CTCs • PTEN • PTPRC • RB1 • TP53

A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death-Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma. (PubMed, Clin Cancer Res) - "These results suggest a lack of cross-resistance with standard of care and support the translational value of the Vk*MYC model system. Further clinical investigation of PT-112 is warranted in multiple myeloma."

Journal • P1 data • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

PT-112 in Subjects With Thymoma and Thymic Carcinoma (clinicaltrials.gov) - P2 | N=53 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Jun 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Thymic Carcinoma • Thymic Epithelial Tumor • Thymoma • Thymus Cancer

Preliminary phase 2 results of PT-112 monotherapy in late-line metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2025) - P2 | "In the more mature Arm 2, OS in pts without prior cabazitaxel (22 pts) was 16.4m and without cabazitaxel or PSMA-Lu-177 (17 pts) was 20.5m. PT-112 treatment resulted in a manageable and reasonably low rate of G3-4 TRAEs and was active in pts with very late-line mCRPC. The better balance of safety and efficacy in Arms 2 and 3 is indicative of an optimized RP3D. Biomarker responses (ALP, CTC and T cell) may reflect broad activity of PT-112."

IO biomarker • Metastases • Monotherapy • P2 data • Anemia • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Promontory Therapeutics Announces Successful End of Phase 2 Meeting with US FDA on Phase 3 Registrational Study Design for PT-112 in Patients with Metastatic Castration-Resistant Prostate Cancer (PRNewswire) - "Promontory Therapeutics...announced a successful in-person End of Phase 2 (EOP2) Meeting with the U.S. Food and Drug Administration (FDA), allowing the company to prepare and submit a registrational Phase 3 study of PT-112 monotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Consistent with FDA Project Optimus, the FDA agreed with the proposed dosing regimen for use in a prospective, randomized controlled Phase 3 registrational study, on the basis of the completed Phase 2 clinical trial. The study design and endpoints, along with the proposed comparator and statistical framework, were agreed in principle, as were Promontory's proposed patient population within mCRPC, and proposal for an interim analysis....Preliminary PT-112 Phase 2 clinical outcomes in metastatic castration-resistant prostate cancer patients will be presented at the ASCO 2025 Annual Meeting."

FDA event • P2 data • Castration-Resistant Prostate Cancer

Partial mitochondrial involvement in the antiproliferative and immunostimulatory effects of PT-112. (PubMed, Oncoimmunology) - "Conversely, PT-112 retained antiproliferative effects and its capacity to drive type I IFN secretion as well as CALR, MHC Class I and PD-L1 exposure on the cell surface irrespective of MOMP defects. These data indicate a partial involvement of MOMP in the mechanisms of action of PT-112, suggesting that PT-112 is active across various tumor types, including malignancies with MOMP defects."

IO biomarker • Journal • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • CALR • HMGB1

Anti-cancer immune effects of PT-112 monotherapy across two disease indications (AACR 2025) - P2 | "In line with prior non-clinical and clinical findings, data from these ongoing Phase II trials show that PT-112 induces robust signals of immune activation and ICD across the adaptive and innate immune systems and are indicative that PT-112's immune effects play a significant role in its anti-cancer mechanism."

IO biomarker • Monotherapy • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Thymic Epithelial Tumor • Thymus Cancer • CD4 • CD8 • GZMB • IFNG • PD-L1 • TGFB1 • TNFA

Pleiotrophin Activates cMet- and mTORC1-Dependent Protein Synthesis through PTPRZ1-The Role of ανβ3 Integrin. (PubMed, Int J Mol Sci) - "The cMet tyrosine kinase inhibitor crizotinib abolishes the stimulatory effects of PTN or PTPRZ1 deletion on mTORC1 activation and protein synthesis, suggesting that mTORC1 activation is downstream of cMet. The mTORC1 inhibitor rapamycin abolishes the stimulatory effect of PTN or PTPRZ1 deletion on endothelial cell migration, suggesting that mTORC1 is involved in the PTN/PTPRZ1-dependent cell migration. The αvβ3 integrin blocking antibody LM609 and the peptide PTN112-136, both known to bind to ανβ3 and inhibit PTN-induced endothelial cell migration, increase cMet phosphorylation and activate mTORC1, suggesting that cMet and mTORC1 activation are required but are not sufficient to stimulate cell migration. Overall, our data highlight novel aspects of the signaling pathway downstream of the PTN/PTPRZ1 axis that regulates endothelial cell functions."

Journal • EIF4EBP1 • HIF1A • PTN • PTPRZ1

Cancer cell-selective induction of mitochondrial stress and immunogenic cell death by PT-112 in human prostate cell lines. (PubMed, J Transl Med) - "Our data provide additional insight into mitochondrial stress and ICD in response to PT-112. PT-112 anticancer immunogenicity could have clinical applications and is currently under investigation in a Phase 2 mCRPC study."

Immunogenic cell death • Journal • Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CASP3

Predictive Value of Neutrophil-to-Lymphocyte Ratio (NLR) and Absolute Lymphocyte Count (ALC) In Thymic Epithelial Tumors (IASLC-WCLC 2024) - "Methods : This single-institution, retrospective analysis was conducted on data obtained between 05/2012 and 03/2023 from four phase II clinical trials evaluating immunomodulatory treatments in metastatic TETs: avelumab (A), bintrafusp alfa (B), PT-112 (P) and sunitinib (S). Potential reasons include small cohort size and heavy pretreatment affecting immune response. Long term follow-up in a larger cohort is needed."

Oncology • Solid Tumor • Thymoma • Thymus Cancer

A Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered PT-112 Injection in Subjects With Advanced Solid Tumors and Subsequent Dose Expansion Cohorts (clinicaltrials.gov) - P2 | N=109 | Active, not recruiting | Sponsor: Promontory Therapeutics Inc. | Recruiting ➔ Active, not recruiting | N=180 ➔ 109

Enrollment change • Enrollment closed • Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • Urology

Promontory Therapeutics Completes Enrollment of Phase 2 Trial of PT-112 in Late-Line Patients with Metastatic Castration-Resistant Prostate Cancer (PRNewswire) - "Promontory Therapeutics Inc...has completed enrollment of its Phase 2 clinical trial of lead therapeutic candidate, PT-112, reaching its target enrollment of 109 patients with late-line metastatic castration-resistant prostate cancer (mCRPC) (ClinicalTrials.gov Identifier: NCT02266745)...Promontory Therapeutics plans for a Type C meeting with the FDA in the second half of 2024, followed by an End-of-Phase 2 meeting with FDA and further engagement with European regulatory authorities....'We look forward to presenting topline safety, efficacy, and correlative data at relevant research and medical conferences later this year.'"

Enrollment closed • European regulatory • FDA event • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

PAVE-1: A Dose Escalation and Confirmation Study of PT-112 in Advanced Solid Tumors in Combination With Avelumab (clinicaltrials.gov) - P1/2 | N=68 | Completed | Sponsor: Promontory Therapeutics Inc. | Active, not recruiting ➔ Completed | Phase classification: P1b/2a ➔ P1/2

Combination therapy • Metastases • Phase classification • Trial completion • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Molecular mechanisms of immunogenic cell death driven by PT-112 (SITC 2023) - "Despite these and other open questions, PT-112 stands out as a powerful immunotherapeutic agent with promising clinical activity in patients with a variety of tumors1 under Phase II clinical development for cancer therapy. 2–8"

Immunogenic cell death • IO biomarker • Oncology • BAK1 • BCL2 • CALR • EIF2S1 • HMGB1

Promontory Therapeutics Presents Data on Molecular Mechanisms of PT-112's Immunogenic Effects (PRNewswire) - "Promontory Therapeutics Inc...today presented data demonstrating the molecular mechanism of its lead therapeutic candidate, PT-112, and its ability to induce immunogenic cell death (ICD) in cancer cells. Data suggest that PT-112-induced ICD is mediated by endoplasmic reticulum (ER) and mitochondrial stresses, which are specific intra-cellular events that comprise part of the larger ICD mechanism. The presentation was made at the Society for Immunotherapy of Cancer's (SITC) 38th Annual Meeting, taking place November 1-5, 2023 in San Diego....PT-112 elicits the phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (EIF2S1, best known as eIF2α), indicating ER stress and the activation of the integrated stress response (ISR)."

Preclinical • Oncology • Solid Tumor

Promontory Therapeutics to Present Data on PT-112 Mechanism of Action at the Society for Immunotherapy of Cancer’s 38th Annual Meeting (PRNewswire) - "Promontory Therapeutics Inc...will present a poster demonstrating the molecular mechanism of its lead therapeutic candidate, PT-112, at the Society for Immunotherapy of Cancer's (SITC) 38th Annual Meeting. SITC is taking place November 1-5, 2023 in San Diego."

Preclinical • Oncology • Solid Tumor

Promontory Therapeutics Presents Data on the Molecular Effects of PT-112 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - "Promontory Therapeutics...presented data on its lead therapeutic candidate PT-112, detailing its early molecular effects that culminate in immunogenic cancer cell death (ICD). The presentation was made at the American Association for Cancer Research (AACR) - National Cancer Institute (NCI) - European Organisation for Research and Treatment of Cancer (EORTC) International Conference on Molecular Targets and Cancer Therapeutics....At early timepoints in prostate cancer cells, PT-112 caused evident nucleolar protein translocation, a hallmark of nucleolar stress and disruption of RiBi. Consistent with the above, PT-112 induced statistically significant repression of pathways related to RiBi, ribosomal RNA (rRNA) processing and translation, crossing prostate, renal and lung cancer cell lines."

Preclinical • Lung Cancer • Prostate Cancer • Renal Cell Carcinoma

Promontory Therapeutics Announces Early Phase 2 Clinical Trial Data From the National Cancer Institute, Demonstrating PT-112's Immune Activation in Thymic Epithelial Tumors (PRNewswire) - P2 | N=53 | NCT05104736 | "The National Cancer Institute (NCI),...under formal collaboration with Promontory Therapeutics...presented preliminary results from the Phase 2 clinical trial of Promontory's lead therapeutic candidate, PT-112, in patients with recurrent thymic epithelial tumors (TETs)...at the International Thymic Malignancy Interest Group (ITMIG) 2023 Annual Meeting....Out of a total of eleven patients evaluable for response, one (9%) achieved a partial response, eight achieved stable disease (73%) and two had progressive disease (18%). No new immune-related AEs have been observed. Findings in peripheral blood included an increase in activated T cells, NK cells, and pro-inflammatory cytokines, and a decrease in immunosuppressive serum analytes."

P2 data • Thymic Carcinoma

Promontory Therapeutics Announces Early Phase 2 Clinical Trial Data From the National Cancer Institute, Demonstrating PT-112's Immune Activation in Thymic Epithelial Tumors (PRNewswire) - P2 | N=53 | NCT05104736 | "The National Cancer Institute (NCI)...under formal collaboration with Promontory Therapeutics Inc., a clinical stage pharmaceutical company advancing immunogenic small molecule approaches in oncology, today presented preliminary results from the Phase 2 clinical trial of Promontory's lead therapeutic candidate, PT-112, in patients with recurrent thymic epithelial tumors (TETs)....Additional preliminary results include: Out of a total of eleven patients evaluable for response, one (9%) achieved a partial response, eight achieved stable disease (73%) and two had progressive disease (18%). No new immune-related AEs have been observed. Findings in peripheral blood included an increase in activated T cells, NK cells, and pro-inflammatory cytokines, and a decrease in immunosuppressive serum analytes."

P2 data • Oncology • Solid Tumor • Thymic Carcinoma • Thymoma • Thymus Cancer

Promontory Therapeutics to Present Molecular Effects of PT-112 at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire) - "Promontory Therapeutics Inc...will present a poster on lead therapeutic candidate, PT-112, and its early molecular effects culminate in immunogenic cancer cell death (ICD), at the American Association for Cancer Research (AACR) – National Cancer Institute (NCI) – European Organisation for Research and Treatment of Cancer (EORTC) International Conference on Molecular Targets and Cancer Therapeutics. The poster will detail PT-112's ability to cause ribosomal biogenesis inhibition and organelle stress in cancer cells."

Preclinical • Oncology

PT-112, a novel immunogenic cell death inducer, causes ribosomal biogenesis inhibition and organelle stress in cancer cells. (AACR-NCI-EORTC 2023) - No abstract available

Immunogenic cell death • Oncology

A Study Evaluating the Safety, Pharmacokinetics, and Clinical Effects of Intravenously Administered PT-112 Injection in Subjects With Advanced Solid Tumors and Subsequent Dose Expansion Cohorts (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Promontory Therapeutics Inc. | Trial completion date: Apr 2024 ➔ Apr 2025 | Trial primary completion date: Jul 2023 ➔ Aug 2024

Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urology

Promontory Therapeutics Expands Phase 2 Trial of PT-112 in Metastatic Castrate-Resistant Prostate Cancer to France (PRNewswire) - "Promontory Therapeutics Inc...has expanded its clinical presence to France. This week the company treated its first four patients in France – at Gustave Roussy and at the Military Hospital (HIA) Bégin in Paris – on the ongoing Phase 2 clinical trial of lead therapeutic candidate, PT-112, in patients with late-stage metastatic castration-resistant prostate cancer (mCRPC)....Within France, the study is being led by primary investigator Dr. Karim Fizazi, MD, PhD, medical oncologist at Gustave Roussy, and professor of oncology at the University of Paris-Saclay."

Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Preliminary efficacy, safety, and immunomodulatory effects of PT-112 from a phase 2 proof of concept study in patients (pts) with thymic epithelial tumors (TETs). (ASCO 2023) - P2 | "Median number of prior systemic therapies is 2.5 (range, 1-4) and all pts have received cisplatin, paclitaxel, or both previously. PT-112 is safe and clinically active in pts with recurrent TETs. In contrast to ICIs, no new irAEs were observed. Immune analyses show evidence of early treatment-related immune activation and support the rationale underlying this novel treatment approach for TETs."

Clinical • Immunomodulating • P2 data • Anemia • Fatigue • Hematological Disorders • Immune Modulation • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Solid Tumor • Thymic Carcinoma • Thymoma • Thymus Cancer • CD27 • CD40LG • CD8 • IFNG • TNFA

Promontory Therapeutics Announces Preliminary Data from the National Cancer Institute Phase 2 Clinical Trial of PT-112 in Thymoma and Thymic Carcinoma at 2023 ASCO Annual Meeting (PRNewswire) - P2 | N=53 | NCT05104736 | "Promontory Therapeutics...announces preliminary data from a Phase 2 clinical trial of the company's lead therapeutic candidate, PT-112, in patients with recurrent thymic epithelial tumors (TETs), specifically thymoma and thymic carcinoma....'Based on preliminary data to date, PT-112 appears to be safe and tolerable, and clinically active in patients with recurrent TETs. The initial translational evidence of PT-112 immune activation is encouraging and supportive of further investigation,' said Promontory Therapeutics Chief Medical Officer Johan Baeck, MD."

P2 data • Oncology • Solid Tumor • Thymic Carcinoma • Thymoma