FN-1501 / Fosun Pharma - LARVOL DELTA

FN-1501 Synergistically Enhances Almonertinib Efficacy in EGFR-TKI-Resistant Lung Adenocarcinoma through Ferroptosis Induction. (PubMed, Anticancer Agents Med Chem) - "FN-1501 exhibits significant antitumor activity and, when combined with Alm, effectively reverses EGFR-TKI resistance by inducing ferroptosis, highlighting its potential for clinical application."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NCOA4

FN-1501 Inhibits Diffuse Large B-Cell Lymphoma Tumor Growth by Inducing Cell Cycle Arrest And Apoptosis. (PubMed, Anticancer Agents Med Chem) - "FN-1501 shows promising anti-tumor activity against DLBCL in vivo and in vitro, suggesting its potential as a new therapeutic option for patients with refractory or relapsed DLBCL."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Synergy and antagonism between azacitidine and FLT3 inhibitors. (PubMed, Comput Biol Med) - "We sought to determine whether combination of azacitidine with a FLT3 inhibitor (gilteritinib, quizartinib, LT-850-166, FN-1501 or FF-10101) displayed synergy or antagonism. The results show that combinations that involved non-covalent FLT3 inhibitors, including the two clinically approved drugs gilteritinib and quizartinib were antagonistic. On the other hand combinations with the covalent inhibitor FF-10101 had some range of concentrations where synergy was observed."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Overexpression of ABCB1 confers resistance to FLT3 inhibitor FN-1501 in cancer cells: in vitro and in vivo characterization. (PubMed, Am J Cancer Res) - "In sum, we demonstrate that FN-1501 is a substrate of ABCB1 transporter from both in vivo and in vitro studies. Therefore, our findings provide new insight on the mechanism of chemoresistance due to ABCB1 overexpression."

Journal • Preclinical • Acute Myelogenous Leukemia • Oncology • Solid Tumor • ABCB1 • FLT3

PROTAC-mediated CDK degradation differentially impacts cancer cell cycles due to heterogeneity in kinase dependencies. (PubMed, Br J Cancer) - "Resistance to CDK4/6 inhibition could be overcome by pharmacologically limiting Cyclin E/CDK2 complex and proves to be a potential therapeutic approach."

Heterogeneity • Journal • Oncology • Targeted Protein Degradation • CDKN2A

Sclerodermatous eruption in a patient with metastatic colon cancer treated with an FLT3/CDK inhibitor. (PubMed, Australas J Dermatol) - No abstract available

Journal • Metastases • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Fibrosis • Gastrointestinal Cancer • Immunology • Oncology • Scleroderma • Solid Tumor • Systemic Sclerosis

A Multicenter, Open-Label, Phase I/II Study of FN-1501 in Patients with Advanced Solid Tumors. (PubMed, Cancers (Basel)) - P1 | "FN-1501 demonstrated reasonable safety, tolerability, and preliminary activity against solid tumors in doses up to 170 mg. Dose escalation was terminated based on 2 DLTs occurring at the 226 mg dose level."

Journal • Metastases • P1/2 data • Acute Myelogenous Leukemia • Cardiovascular • Fatigue • Heart Failure • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Thrombocytopenia • ALK • CDK4 • FLT3 • KDR • KRAS • NRAS • TP53

Rational design of 4-((6-phenoxypyrimidin-4-yl)amino)-N-(4-(piperazin-1-yl)phenyl)-1H-pyrazole-3-carboxamide (LT-540-717) as orally bioavailable FLT3 inhibitor. (PubMed, Eur J Med Chem) - "Herein, we describe the discovery of compound LT-540-717 (32), a potent FLT3 inhibitor (IC: 0.62 nM), starting from FN-1501...Furthermore, 32 showed an acceptable bioavailability (F = 33.3% in rat and 72.7% in beagles), a suitable half-life time (T = 3.5 h in rat and T = 11.1 h in beagles), and a satisfactory metabolic stability. In summary, these results show the therapeutic potential of 32 to become a new anti-AML drug, especially for AML harboring dual FLT3 (ITD, TKD) mutations."

Journal • Acute Myelogenous Leukemia • Oncology • FLT3

A multicenter, open-label, phase I/II study of FN-1501 in patients with advanced solid tumors and acute myeloid leukemia. (ASCO 2022) - P1 | "FN-1501 IV has shown reasonable safety, tolerability, and preliminary activity against solid tumors up to 170 mg. Dose escalation was terminated based on 2 DLTs occurring at the 226 mg dose level."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Cardiovascular • Endometrial Cancer • Fatigue • Heart Failure • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • Thrombocytopenia • Thymoma • Thymus Cancer • ALK • CDK4 • FLT3 • KDR • KRAS • NRAS • TP53

A Phase 1 Study to Evaluate FN-1501 Monotherapy in Patients With Advanced Solid Tumors and R/R AML (clinicaltrials.gov) - P1 | N=67 | Terminated | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd. | Trial completion date: Jun 2022 ➔ Feb 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2022 ➔ Feb 2022; Despite demonstrated safety and tolerability the trial was terminated early due to program re-prioritization in light of the competitive landscape.

Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

A Phase 1 Study to Evaluate FN-1501 Monotherapy in Patients With Advanced Solid Tumors and R/R AML (clinicaltrials.gov) - P1 | N=67 | Active, not recruiting | Sponsor: Shanghai Fosun Pharmaceutical Development Co, Ltd. | Recruiting ➔ Active, not recruiting | N=33 ➔ 67 | Trial completion date: Sep 2021 ➔ Apr 2022 | Trial primary completion date: Sep 2021 ➔ Apr 2022

Enrollment change • Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

[VIRTUAL] A Phase I safety and tolerance study of FN-1501, a novel FLT3 inhibitor, in patients with advanced solid tumors and acute myeloid leukemia (AACR 2021) - P1 | "FN-1501 has demonstrated reasonable safety/tolerability across all doses tested, with promising anti-tumor activity in pts with certain advanced, heavily pre-treated solid tumors. Enrollment of pts into the dose escalation part of the study is continuing and updated safety, PK and molecular biomarker results will be presented at the meeting."

Clinical • P1 data • Acute Myelogenous Leukemia • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ALK • CDK4 • FLT3 • KRAS • NRAS • TP53

A Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of FN-1501 monotherapy in patients with advanced solid tumors. (ASCO 2019) - P1; "Enrollment to cohort 3 is on-going. Clinical trial information: NCT03690154"

Clinical • Monotherapy • P1 data • PK/PD data

A Phase 1 Study to Evaluate FN-1501 Monotherapy in Patients With Advanced Solid Tumors and R/R AML (clinicaltrials.gov) - P1; N=33; Recruiting; Sponsor: Shanghai Fosun Pharmaceutical Development Co, Ltd.; Trial completion date: Jun 2020 ➔ Sep 2021; Trial primary completion date: Jun 2020 ➔ Sep 2021

Clinical • Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • MRI

Fosun's novel FLT3-targeted AML therapy gains tacit clinical approval in China (GBI Health) - "The Center for Drug Evaluation website indicates that Shanghai Fosun Pharmaceutical (Group) Co., Ltd’s (600196.SH) novel small-molecule chemical drug FN-1501, a potential treatment for acute myeloid leukemia (AML), has obtained tacit clinical trial approval. The targeted indication is advanced malignancy."

Non-US regulatory • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

CRMP2 is a therapeutic target that suppresses the aggressiveness of breast cancer cells by stabilizing RECK. (PubMed, Oncogene) - "Pharmacologic rescue of CRMP2 expression suppressed breast cancer metastasis in vitro and in vivo and stimulated a synergetic effect with FN-1501 that induces CRMP2 dephosphorylation. Collectively, this study highlights the potential of CRMP2 as a therapeutic target in breast cancer metastasis and reveals a distinct mechanism of CRMP2."

Journal • Breast Cancer • Oncology • Solid Tumor • CRMP

[VIRTUAL] FIH phase I dose escalation study of FN1501, an investigational FLT-3 inhibitor with multiple targets in patients with relapsed or refractory solid tumors and acute myeloid leukemia. (ASCO 2020) - "This on-going Ph1trial of FN1501 is providing evidence of dose or exposure effects as a single agent in patients with solid tumors. Since FN1501 targets multiple kinases on addition to FLT3, antitumor activity beyond AML is also being observed, suggesting that the potent inhibitory effects of other tyrosine kinases, including EGFR2 may be playing a role in the regulation of cellular functions, cell growth, differentiation and angiogenesis effects. FN1501 has been well tolerated and AEs are manageable."

Clinical • P1 data • Acute Myelogenous Leukemia • Endometrial Cancer • Gynecologic Cancers • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thoracic Cancer • Thymus Cancer • ALK • CDK4 • FLT3 • STAT5

Design and Synthesis of 4-(Heterocyclic Substituted Amino)-1H-Pyrazole-3-Carboxamide Derivatives and Their Potent Activity against Acute Myeloid Leukemia (AML). (PubMed, Int J Mol Sci) - "By modifying the structure of FN-1501, a potent FLT3 inhibitor, 24 novel 1H-pyrazole-3-carboxamide derivatives were designed and synthesized...In addition, compound 8t significantly inhibited the proliferation of most human cell lines of NCI60 (GI < 1 μM for most cell lines). Taken together, these results demonstrated the potential of 8t as a novel compound for further development into a kinase inhibitor applied in cancer therapeutics."

Journal

Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activity of FN-1501 Monotherapy in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=33; Recruiting; Sponsor: Shanghai Fosun Pharmaceutical Development Co, Ltd.; Trial completion date: Aug 2019 ➔ Jun 2020; Trial primary completion date: Aug 2019 ➔ Jun 2020

Clinical • Monotherapy • Trial completion date • Trial primary completion date • MRI