pulrodemstat (CC-90011) / BMS - LARVOL DELTA

Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies. (PubMed, Cancer) - P1 | "The safety profile of CC-90011 suggested that its reversible mechanism of action may provide an advantage over other irreversible LSD1 inhibitors. The favorable tolerability profile, clinical activity, durable responses, and once-per-week dosing support further exploration of CC-90011 as monotherapy and in combination with other treatments for patients with advanced solid tumors and other malignancies."

Clinical • Journal • Endocrine Cancer • Hematological Disorders • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Neuroendocrine Tumor • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Thrombocytopenia • GRP-10

Pharmacological inhibition of LSD1 suppresses the CD155/TIGIT immune checkpoint axis and enhances NK cell-mediated cytotoxicity in colorectal cancer. (PubMed, Bioorg Chem) - "Importantly, pharmacological inhibition of LSD1 with two small-molecule inhibitors, CC-90011 and ORY-1001, markedly decreased CD155 expression and membrane abundance in multiple CRC cell lines. Collectively, these findings reveal that pharmacological inhibition of LSD1 attenuates CRC immune escape, at least in part, by epigenetically suppressing the CD155/TIGIT axis. This study provides a rationale for exploiting LSD1 inhibitors as immunomodulatory agents to enhance antitumor immunity in CRC."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • IFNG • PVR • TIGIT • TNFA

Biomimetic M2 exosome-based dual-drug nanoplatform for combined immunomodulation and bone protection in rheumatoid arthritis. (PubMed, Bioact Mater) - "Herein, we report the development of biomimetic nanoparticles (CEC NPs) that co-deliver celecoxib (CXB) and the lysine-specific demethylase 1 (LSD1) inhibitor CC-90011 via M2 macrophage-derived exosomes (M2 Exos), thereby integrating targeted delivery with innovative multi-mechanistic therapeutic strategies. In a collagen-induced arthritis (CIA) model, CEC NPs markedly outperform monotherapies, with pronounced reduction in joint swelling, cartilage degradation, and bone erosion, without systemic toxicity. This work introduces an M2 Exo-based dual-drug delivery system as a versatile strategy for multi-mechanistic modulation of inflammation and bone destruction, offering a promising paradigm that could be extended to other inflammatory and autoimmune bone disorders."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Orthopedics • Rheumatoid Arthritis • Rheumatology • NFATC1

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Recruiting | Sponsor: Celgene | Trial completion date: Apr 2023 ➔ Mar 2024

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Recruiting | Sponsor: Celgene | Trial primary completion date: Sep 2021 ➔ Dec 2021

Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Recruiting | Sponsor: Celgene | Trial completion date: Dec 2022 ➔ Apr 2023

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=18 | Recruiting | Sponsor: Celgene | Trial completion date: Mar 2022 ➔ Sep 2022

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Active, not recruiting | Sponsor: Celgene | Trial completion date: Jun 2024 ➔ Feb 2024 | Trial primary completion date: Sep 2023 ➔ Feb 2024

Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=90 | Completed | Sponsor: Celgene | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=90 | Active, not recruiting | Sponsor: Celgene | Phase classification: P1b ➔ P1 | Trial completion date: Feb 2024 ➔ Jun 2024 | Trial primary completion date: Feb 2024 ➔ Jun 2024

Phase classification • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Recruiting | Sponsor: Celgene | N=18 ➔ 90 | Trial primary completion date: Dec 2019 ➔ Sep 2021

Enrollment change • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=32 | Not yet recruiting | Sponsor: Celgene

New P1 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Recruiting | Sponsor: Celgene | Trial completion date: Mar 2024 ➔ Jul 2024

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Recruiting | Sponsor: Celgene | Trial primary completion date: Dec 2021 ➔ Apr 2023

Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=18 | Recruiting | Sponsor: Celgene | Not yet recruiting ➔ Recruiting | N=32 ➔ 18 | Trial completion date: Aug 2022 ➔ Mar 2022

Enrollment change • Enrollment open • Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Recruiting | Sponsor: Celgene | Trial primary completion date: May 2023 ➔ Sep 2023

Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Safety, Tolerability and Preliminary Efficacy Evaluation of CC-90011 Given in Combination With Cisplatin and Etoposide in Subjects With First Line, Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1b | N=90 | Recruiting | Sponsor: Celgene | Trial completion date: Sep 2022 ➔ Dec 2022

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Novel Synthetic Route for Lysine-Specific Demethylase 1-Targeting Compounds: CC-90011 and MS9117. (PubMed, ChemMedChem) - "Herein, we present a novel synthetic route to LSD1-targeting compounds that enables late-stage diversification; the key intermediate LYY-23 was used to synthesize CC-90011 and MS9117. In addition, compounds LYY-25 ∼ LYY-29 were synthesized and evaluated for LSD1 inhibition, all of which showed inhibitory activity, with LYY-28 emerging as the most potent compound (IC50 = 3.59 nM)."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Targeted Protein Degradation

Upregulation of SSTR2 expression and radioligand binding of [18F]SiTATE in neuroendocrine tumour cells with combined inhibition of class I HDACs and LSD1. (PubMed, Neuroendocrinology) - "Combined inhibition of class I HDACs and LSD1 potently increases SSTR2 expression and consequently radioligand binding and might thus be a putative strategy to improve the outcome of PRRT therapy in patients with NETs."

Journal • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR • SSTR2

Pulrodemstat, a selective inhibitor of KDM1A, suppresses head and neck squamous cell carcinoma growth by triggering apoptosis. (PubMed, BMC Pharmacol Toxicol) - "Pulrodemstat is an effective therapeutic drug for HNSCC. Thus, the TET3/KDM1A axis may account for the malignant phenotype of HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • KDM1A

Anticancer Drugs of Lysine Specific Histone Demethylase-1 (LSD1) Display Variable Inhibition on Nucleosome Substrates. (PubMed, Biochemistry) - "Here, the inhibition kinetics on the H3K4me2 peptide and nucleosome substrates was examined, comparing the rates of demethylation in the presence of reversible [CC-90011 (PD) and SP-2577 (SD)] and irreversible [ORY-1001 (ID) and tranylcypromine (TCP)] inhibitors. These data show that SP-2577 is not an LSD1 enzyme inhibitor, although the drug may function independent of demethylation due to its cytotoxic selectivity in TC-32 cells. Taken together, this work highlights the pitfalls of using coupled assays to ascribe a drug's mode of action, emphasizes the use of physiologically relevant substrates in epigenetic drug targeting strategies, and provides insight into the development of substrate-selective inhibitors of LSD1."

Epigenetic controller • Journal • Acute Myelogenous Leukemia • Ewing Sarcoma • Hematological Malignancies • Leukemia • Lung Cancer • Oncology • Sarcoma • Small Cell Lung Cancer • Solid Tumor

A Safety and Efficacy Study of CC-90011 in Participants With Relapsed and/or Refractory Solid Tumors and Non-Hodgkin's Lymphomas (clinicaltrials.gov) - P1 | N=75 | Terminated | Sponsor: Celgene | Trial completion date: Sep 2025 ➔ Mar 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2025 ➔ Mar 2024; Business objectives have changed

Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib. (PubMed, Discov Oncol) - "Pulrodemstat synergized with Lenvatinib based on suppression of PI3K-AKT signaling and activation of apoptotic signaling."

Journal • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • CASP3

A Safety and Efficacy Study of CC-90011 in Combination With Nivolumab in Subjects With Advanced Cancers (clinicaltrials.gov) - P2 | N=92 | Completed | Sponsor: Celgene | Active, not recruiting ➔ Completed

Combination therapy • Metastases • Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology