derazantinib (ARQ 087) / Roivant, Merck (MSD) - LARVOL DELTA

Antibacterial and anti-biofilm activities of Derazantinib (ARQ-087) against Staphylococcus aureus. (PubMed, Arch Microbiol) - "These findings highlight ARQ-087 as a promising therapeutic candidate for treating MRSA infections and biofilm-associated diseases. Further preclinical studies are needed to confirm its potential for clinical application."

Journal • Infectious Disease

Tumor vascularity as a predictor of FGFR inhibitor response in FGFR2-fused intrahepatic cholangiocarcinoma. (ASCO-GI 2025) - "The cohort included pts treated with futibatinib (n=16), infigratinib (n=16), pemigatinib (n=36), and derazantinib (n=5)...For FGFR2-fused iCCA, median PFS for first-line gemcitabine-based chemotherapy with or without immunotherapy was 4.07 months [3.0-5.1]... Pts with FGFR2-fused iCCA have a shorter PFS on first-line chemotherapy, and PFS outcomes for FGFR inhibitors were consistent with existing data. Tumor vascularity, as assessed by CT imaging, may be a valuable predictor of response to FGFR inhibitors. This study suggests that hypervascular tumors may have better outcomes, warranting further investigation in a larger cohort to confirm these findings and establish tumor vascularity as a predictive biomarker for FGFR inhibitor therapy."

IO biomarker • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2

EFFICACY AND SAFETY OF FGFR INHIBITORS IN CHOLANGIOCARCINOMA, A SYSTEMATIC REVIEW AND META ANALYSIS (AASLD 2024) - "Current treatment strategies include surgery, radiation and chemotherapy consisting mainly of 5-fluorouracil, gemcitabine and cisplatin... A total of 1086 articles were screened and we included 9 clinical trials(3 Derazantinib, 1 Pemigatinib, 1 Infigratinib, 1 Futibatinib, 2 Erdafatinib, 1 Ponatinib)... FGFR inhibitors present a promising targeted approach adding to the arsenal of drugs available for the treatment of cholangiocarcinoma. Continued research efforts and Phase 3 trial data are crucial to understand the efficacy, outcomes and safety profile of these novel drugs."

Retrospective data • Review • Anemia • Biliary Cancer • Cholangiocarcinoma • Dental Disorders • Gastrointestinal Cancer • Hematological Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Septic Shock • Solid Tumor • Stomatitis

Treatment of Atezolizumab and Derazantinib in Patients With Advanced iCCA With FGFR2 Fusions/Rearrangements (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2

Clinical response to futibatinib in intrahepatic cholangiocarcinoma with acquired resistance to fibroblast growth factor receptor 2 inhibitors (ESMO-GI 2024) - "However, limited evidence has been presented to date for the efficacy of futibatinib in patients progressing under treatment with a non-covalent inhibitor. Between January 2021 and April 2023, 14 patients received futibatinib after treatment with the non-covalent FGFR inhibitors pemigatinib (10 patients) or derazantinib (4 patients). Futibatinib was manageable and active in patients with iCCA progressing under a previously non-covalent FGFR2 inhibitor. Randomized controlled trials are needed to determine the optimal therapeutic approach between an upfront treatment with a covalent inhibitor or a sequential strategy starting with a non-covalent inhibitor, followed by a covalent one if disease progresses due to acquired mutations that this could address."

Clinical • Preclinical • Biliary Cancer • Cholangiocarcinoma • Dermatology • Gastrointestinal Cancer • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • FGFR2

Derazantinib alone and with atezolizumab in metastatic urothelial carcinoma with activating FGFR aberrations. (PubMed, JNCI Cancer Spectr) - "Derazantinib as monotherapy or in combination with atezolizumab was well-tolerated but did not show sufficient efficacy to warrant further development in mUC."

Journal • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR • FGFR1

FIDES-03: Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=47 | Terminated | Sponsor: Basilea Pharmaceutica | Phase classification: P1b/2 ➔ P1/2

Combination therapy • Monotherapy • Phase classification • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • HER-2

The role of tumor molecular profiling in patients with advanced biliary tract cancer receiving systemic treatment (LCS 2024) - "51 pts (65%) received cisplatin-based first-line systemic therapy...9 pts (11%) received targeted therapy with ivosidenib for IDH1 mutation (2 pts), pemigatinib for FGFR2 rearrangement (1 pt), derazantinib for FGFR2 mutation (3 pts), zanidatamab for HER2 amplification (2 pts), encorafenib for BRAF mutation (1 pt): mOS was 39 mos (95% CI 28-NR) vs 26 (95% CI 16-NR, p = 0.551)... In our study, no molecular alteration showed a clear prognostic value, although pts with CDKN2A, TP53, and KRAS mutations had worse clinical outcomes. mOS was numerically longer in pts receiving targeted therapy, and in those with IDH1 mutated or FGFR2 rearranged tumors, but failed to reach statistical significance, probably due to the small sample size. Larger studies could provide additional information regarding the prognostic and predictive value of pivotal molecular alterations in BTC."

Clinical • Metastases • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • ARID1A • BAP1 • BRAF • CDKN2A • FGFR2 • HER-2 • IDH1 • KRAS • TP53

Derazantinib Inhibits the Bioactivity of Keloid Fibroblasts via FGFR Signaling. (PubMed, Biomedicines) - "Also, derazantinib inhibited the expression of FGFR1 and PAI-1 and reduced the weight of the implanted keloid from the xenograft mice model. These findings suggest that derazantinib may be a potent therapy for keloids via FGFR signaling."

Journal • Dermatopathology • Fibrosis • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • FGFR1

Efficacy and safety of derazantinib (DZB) in patients with metastatic urothelial carcinoma (mUC) with activating FGFR1/2/3 genetic aberrations (GA): Results from the phase 1b/2 FIDES-02 study. (ASCO-GU 2023) - P1b/2, P2 | "Derazantinib showed signals of clinical activity in some patients with mUC and FGFR1-3 GA but the observed ORR and PFS did not meet contemporary benchmarks that would support further clinical development of derazantinib as monotherapy in this indication. Derazantinib showed a well-manageable safety profile with low rates of hand-foot syndrome, stomatitis, nail toxicity and retinal side effects. Clinical trial information: NCT04045613."

Clinical • Metastases • P1/2 data • Oncology • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR2 • FGFR3 • TACC3

FIDES-02 Data Fail to Support the Development of Derazantinib in Metastatic Urothelial Cancer (OncLive) - P1b/2 | N=95 | FIDES-02 (NCT04045613) | Sponsor: Basilea Pharmaceutica | "The agent was also evaluated in the multicohort phase 1b/2 FIDES-02 study (NCT04045613) as a single-agent and in combination with atezolizumab (Tecentriq) for patients with metastatic urothelial cancer harboring FGFR1-3 genetic alterations. Data from substudies 1 and 5 (n = 49) were reported at the 2023 Genitourinary Cancers Symposium, demonstrating that derazantinib monotherapy did not meet its primary efficacy end point in either cohort, with a combined overall response rate (ORR) of 8% (95% CI, 3%-20%). Median progression-free survival (PFS) and overall survival (OS) were 2.1 (95% CI, 2.00-2.10) and 6.6 (95% CI, 4.44-8.15) months, respectively."

P1/2 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Lack of pharmacokinetic interaction between derazantinib and naringin in rats. (PubMed, Pharm Biol) - "A Xevo TQ-S triple quadrupole tandem mass spectrometer was used for mass spectrometry monitoring in selective reaction monitoring (SRM) mode with transitions of m/z 468 96 → 382.00 for derazantinib and m/z 488.01 → 400.98 for pemigatinib, respectively. Co-administration of naringin with derazantinib was not associated with significant changes in pharmacokinetic parameters. Thus, this study suggests that the combination of derazantinib with naringin can safely be administered concomitantly without dose adjustment."

Journal • PK/PD data • Preclinical • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR1 • FGFR2 • FGFR3

Efficacy and safety of derazantinib (DZB) in patients with metastatic urothelial carcinoma (mUC) with activating FGFR1/2/3 genetic aberrations (GA): Results from the phase 1b/2 FIDES-02 study (EAU 2023) - P1b/2, P2 | No abstract available

Clinical • Metastases • P1/2 data • Oncology • Solid Tumor • Urothelial Cancer • FGFR1

[VIRTUAL] Differential induction of gene expression may explain differences in reported adverse event profiles between the FGFR-inhibitors derazantinib and erdafitinib: An analysis in safety relevant normal tissues from urothelial cancer (UC) patient-derived mouse xenograft (PDX) models (ESMO 2020) - P1b/2 | "Legal entity responsible for the study: Basilea Pharmaceutica International Ltd. Funding: Basilea Pharmaceutica International Ltd."

Adverse events • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

FIDES-02, a phase Ib/II study of derazantinib (DZB) as monotherapy and combination therapy with atezolizumab (A) in patients with surgically unresectable or metastaticurothelial cancer (UC) and FGFR genetic aberrations. (ASCO-GU 2020) - P1b/2; "Preclinical data show that DZB reduced CSF1-stimulated CSF1R phosphorylation in macrophages, with a maximal effect similar to the CSF1R inhibitor BLZ945, suggesting DZB could have an effect on tumor-associated macrophage regulation...Cohort 1 (C1) enrolls pts after one or more standard chemotherapy ± ICB regimens (Phase 2; treatment: DZB); C2 enrolls patients with any advanced solid tumor, any FGFR status, any prior treatment (Phase 1b; for RP2D of DZB+A); C3 enrolls first-line patients with cisplatin-ineligible, PD-L1-low UC (Phase 2; DZB v DZB+A); C4 enrolls UC patients resistant to FGFR inhibitor treatment (Phase 2; DZB v DZB+A)...Clinical trial information: NCT04045613. Research Funding: Basilea Pharmaceutica International Ltd."

Clinical • Combination therapy • IO biomarker • Monotherapy • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR1 • PD-L1

Derazantinib, an inhibitor of fibroblast growth factor receptors 1-3, increases the efficacy of paclitaxel combined with a VEGFR2-antibody in murine syngeneic tumor models (AACR-NCI-EORTC 2022) - P1b/2 | "DZB is also in a phase-2 trial for gastric cancer (GC), where it is combined with the current standard-of-care (SoC) paclitaxel and the VEGFR2-antibody (Ab), ramucirumab...When the mean tumor size was at least 80 mm3, mice were treated with vehicles (po, ip and iv), DZB alone (35 or 75 mg/kg, po, qd), paclitaxel (15 mg/kg, iv, qw) or the VEGFR2-Ab, DC101 (10 mg/kg, ip, 2qw)... DZB is well-tolerated when combined with paclitaxel and a VEGFR2-Ab in murine syngeneic models, and shows an additive effect in the orthotopic breast models. These data support the ongoing clinical trial with DZB in GC (FIDES-03, NCT04604132). No"

Preclinical • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CSF1R • FGFR

Derazantinib (DZB): A dual FGFR/CSF1R-inhibitor active in PDX-models of urothelial cancer (AACR-NCI-EORTC 2019) - P1b/2; "Bone-marrow derived mouse macrophages were CSF1 starved (12h), pre-incubated with DZB/BLZ945 (30/10m) and stimulated with 0.3 μM CSF1 (3m). DZB is a potent FGFRi and CSF1R inhibitor. Screens in UC models indicate that DZB efficacy is driven by FGFR mutation and expression and, potentially, CSF1R modulation. A clinical trial is ongoing in UC patients (NCT04045613) to assess DZB monotherapy, and combination with the PD-L1 antibody atezolizumab."

IO biomarker • Late-breaking abstract • PD(L)-1 Biomarker • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR2 • FGFR3 • TACC3

Derazantinib, an FGFR1-3 inhibitor, inhibits CSF1R in macrophages and tumor cell lines, and synergizes with a PDL1-antibody in an FGFR-driven murine syngeneic model (AACR 2022) - P1b/2 | "DZB (65-75 mg/kg) and another FGFR-inhibitor, pemigatinib (1 mg/kg) were dosed daily, orally, and the murine PDL1-Antibody (PDL1-Ab) was dosed at 5-10 mg/kg, i.p., 2qw. DZB is a potent inhibitor of CSF1R in vitro. In combination with a murine PDL1-Ab, DZB showed a positive interaction in the orthotopic syngeneic breast tumor model, 4T1, against both the primary tumor and metastases. These data support clinical trials in which DZB is combined with the PDL1-Ab, atezolizumab (NCT04604132, NCT04045613)."

IO biomarker • Preclinical • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • Urothelial Cancer • CSF1R • FGFR1 • FGFR2

FIDES-03: Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma (clinicaltrials.gov) - P1b/2 | N=47 | Terminated | Sponsor: Basilea Pharmaceutica | Completed ➔ Terminated; Terminated prematurely for administrative reasons not related to patient safety.

Combination therapy • Monotherapy • Trial termination • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • HER-2

Derazantinib, a fibroblast growth factor receptor inhibitor, inhibits colony-stimulating factor receptor-1 in macrophages and tumor cells and in combination with a murine programmed cell death ligand-1-antibody activates the immune environment of murine syngeneic tumor models. (PubMed, Anticancer Drugs) - "DZB inhibited growth of three tumor xenograft models with reported expression or amplification of CSF1R, whereas the specific FGFRi, pemigatinib, had no efficacy. Similar modulation of the tumor microenvironment was observed in an FGFR-insensitive syngeneic bladder model, MBT-2. These data confirm CSF1R as an important oncology target for DZB and provide mechanistic insight for the ongoing clinical trials, in which DZB is combined with the PD-L1 antibody, atezolizumab."

Combination therapy • IO biomarker • Journal • Preclinical • Tumor cell • Breast Cancer • Oncology • Solid Tumor • FGFR • FGFR2

The fibroblast growth factor receptor inhibitor, derazantinib, has strong efficacy in human gastric tumor models and synergizes with paclitaxel in vivo. (PubMed, Anticancer Drugs) - "The combination showed synergy (5) or additivity (2), and no antagonism, with synergy significantly associated (P < 0.05) with higher levels of M2-type macrophages. The association of strong efficacy of the combination in vivo with M2 macrophages, which are known to express CSF1R, and the absence of synergy in vitro is consistent with the tumor microenvironment also being a factor in DZB efficacy and suggests additional means by which DZB could be stratified for cancer treatment in the clinic."

Journal • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CSF1R • FGFR • FGFR1

FIDES-03: Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma (clinicaltrials.gov) - P1b/2 | N=47 | Completed | Sponsor: Basilea Pharmaceutica | Active, not recruiting ➔ Completed | Trial completion date: Jul 2023 ➔ Dec 2022 | Trial primary completion date: Jul 2023 ➔ Dec 2022

Combination therapy • Monotherapy • Trial completion • Trial completion date • Trial primary completion date • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • HER-2

FIDES-01: Derazantinib in Subjects With FGFR2 Gene Fusion-, Mutation- or Amplification- Positive Inoperable or Advanced Intrahepatic Cholangiocarcinoma (clinicaltrials.gov) - P2 | N=148 | Completed | Sponsor: Basilea Pharmaceutica | Active, not recruiting ➔ Completed

Trial completion • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2

Efficacy of derazantinib in intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions, mutations or amplifications (ESMO 2022) - P2 | "Pemigatinib and Infigratinib have received accelerated FDA approval for chemorefractory CCA with FGFR2 F . Conclusions Derazantinib results in meaningful clinical benefit for pts with FGFR2 genetic aberrations including FGFR2 F and FGFR2 MA . Derazantinib-related toxicities were limited: PPE, stomatitis, retinal or nail toxicity were infrequent in the study population."

Clinical • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR1 • FGFR2

Efficacy of derazantinib in intrahepatic cholangiocarcinoma patients with FGFR2 mutations or amplifications: Interim results from the phase 2 study FIDES-01. (ASCO-GI 2022) - P2 | "This interim data in study FIDES-01 suggest that derazantinib treatment provides clinical benefit to pts with advanced iCCA harboring FGFR2M/A who progressed after at least one line of standard chemotherapy. To our knowledge, this is the first report of clinically meaningful anti-tumor efficacy in a prospectively planned cohort of iCCA pts harboring FGFR2M/A. The study is ongoing to accrue 43 patients, assessing derazantinib as a therapeutic option for FGFR2M/A+ iCCA pts after disease progression on first-line treatment."

Clinical • P2 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR1 • FGFR2