CPL304110 / Celon Pharma - LARVOL DELTA

Fibroblast Growth Factor Receptor Inhibitors Decrease Proliferation of Melanoma Cell Lines and Their Activity Is Modulated by Vitamin D. (PubMed, Int J Mol Sci) - "We have previously documented that vitamin D and its low-calcaemic analogues enhance the anticancer activity of drugs including a classic chemotherapeutic-dacarbazine-and an antiangiogenic VEGFRs inhibitor-cediranib. In this study, we explored the response of A375 and RPMI7951 melanoma lines to CPL304110 (CPL110), a novel selective inhibitor of fibroblast growth factor receptors (FGFRs), and compared its efficacy with that of AZD4547, the first-generation FGFRs selective inhibitor...Interestingly, 1,25(OH)2D3 and CPL304110 co-treatment resulted in activation of the ERK1/2 pathway in A375 cells. Our results strongly suggested possible crosstalk between vitamin D-activated pathways and activity of FGFR inhibitors, which should be considered in further clinical studies."

Journal • Preclinical • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • FGFR

Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Metastases • Trial completion date • Trial primary completion date • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor

Preclinical characterization of CPL304110 as a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3 for gastric, bladder, and squamous cell lung cancer. (PubMed, Front Oncol) - P1 | "Comparative analyses with FDA-approved FGFR inhibitors, erdafitinib and pemigatinib, revealed certain advantages of CPL304110 in both in vitro and in vivo assessments. Encouraging preclinical results led the way for the initiation of a Phase I clinical trial (01FGFR2018; NCT04149691) to further evaluate CPL304110 as a novel anticancer therapy."

Journal • Preclinical • Bladder Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGFR • FGFR1

Preclinical characterization of CPL304110 as a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3 for gastric, bladder, and squamous cell lung cancer (Front Oncol) - "CPL304110 demonstrated efficacy in both FGFR-dependent cell lines and patient-derived tumor xenograft (PDTX) in vivo models. Comparative analyses with FDA-approved FGFR inhibitors, erdafitinib and pemigatinib, revealed certain advantages of CPL304110 in both in vitro and in vivo assessments."

Preclinical • Bladder Cancer • Gastric Cancer • Non Small Cell Lung Cancer

Preliminary results from a phase IA trial of selective FGFR1-3 inhibitor CPL304110 in patients with FGFR-deregulated advanced solid malignancies (ESMO-TAT 2023) - P1 | "Conclusions The above early study observations suggest that CPL304110 administration is associated with acceptable toxicity and encouraging response rate in heavily pretreated patients with FGFR-aberrant advanced solid malignancies. The final selection of RP2D will take place after the end of phase IB."

Clinical • Metastases • P1 data • Basal Cell Carcinoma • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

[VIRTUAL] Preclinical characterization of CPL304110 as a potential selective inhibitor of fibroblast growth factors 1/2/3 in solid cancers (ESMO 2020) - P1 | "Our drug is currently under clinical investigation – Phase I (NCT04149691). Legal entity responsible for the study: Celon Pharma S.A. Funding: Celon Pharma S.A and NCBR grant."

Preclinical • Bladder Cancer • Endometrial Cancer • Lung Cancer • Oncology • Solid Tumor • FGF • FGFR2 • FGFR3 • FGFR4

Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Metastases • Trial completion date • Trial primary completion date • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Urothelial Cancer

Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Jul 2021 ➔ Dec 2022 | Trial primary completion date: Jul 2021 ➔ Dec 2022

Trial completion date • Trial primary completion date • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Urothelial Cancer

p38 Mediates Resistance to FGFR Inhibition in Non-Small Cell Lung Cancer. (PubMed, Cells) - "Here, we investigated the NSCLC cell lines response and potential mechanism of acquired resistance to novel selective FGFR inhibitor CPL304110...Moreover, the overexpression of this kinase in parental cells led to impaired response to FGFR inhibition, thus confirming that p38 MAPK is a driver of resistance to a novel FGFR inhibitor. Taken together, our results provide an insight into the potential direction for NSCLC targeted therapy."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGFR1

MET-Pyk2 Axis Mediates Acquired Resistance to FGFR Inhibition in Cancer Cells. (PubMed, Front Oncol) - "In this study, we focused on a novel pan-FGFR inhibitor-CPL304110, currently being investigated in phase I clinical trials in adults with advanced solid malignancies...Our results demonstrate that the HGF/MET-Pyk2 signaling axis confers resistance to the novel FGFR inhibitor, and this mechanism is common for lung, gastric, and bladder cancer cells. Our study suggests that targeting of MET/Pyk2 could be an approach to overcome resistance to FGFR inhibition."

Journal • Preclinical • Bladder Cancer • Gastric Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer

Discovery and optimization of novel pyrazole-benzimidazole CPL304110, as a potent and selective inhibitor of fibroblast growth factor receptors FGFR (1-3). (PubMed, Eur J Med Chem) - P1 | "Compound 56q (CPL304110) was identified as a selective and potent pan-FGFR inhibitor for FGFR1, -2, -3 with ICs of 0.75 nM, 0.50 nM, 3.05 nM respectively, whereas IC of 87.90 nM for FGFR4. Due to its favorable pharmacokinetic profile, low toxicity and potent anti-tumor activity in vivo, compound 56q is currently under evaluation in phase I clinical trial for the treatment of bladder, gastric and squamous cell lung cancers (01FGFR2018; NCT04149691)."

Journal • Review • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGFR • FGFR4

Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1; N=42; Recruiting; Sponsor: Celon Pharma SA; Trial completion date: Jul 2020 ➔ Jul 2021; Trial primary completion date: Jul 2020 ➔ Jul 2021

Clinical • Trial completion date • Trial primary completion date • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Urothelial Cancer

Safety, Tolerability and Pharmacokinetics of Oral CPL304110, in Adult Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1; N=42; Recruiting; Sponsor: Celon Pharma SA

Clinical • New P1 trial