fovinaciclib (FCN-437) / Fosun Pharma - LARVOL DELTA

Shanghai Fosun Pharmaceutical…announced that its subsidiary Avanc Pharmaceutical Co., Ltd. has secured National Medical Products Administration (NMPA) approval for a new indication of fovinaciclib, a next‑generation CDK4/6 inhibitor (flcube.com) - "The drug is now authorized for use in combination with an aromatase inhibitor as first‑line endocrine therapy in adults with hormone‑receptor (HR)‑positive, HER2‑negative locally advanced or metastatic breast cancer."

China approval • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Fosun Pharma (02196) subsidiary Aohong Pharmaceutical’s innovative drug Fovinaciclib Citrate Capsules drug registration application was accepted by the CDE [Google translation] (Zhitong Finance) - "Zhitong Finance APP learned that on January 9, Fosun Pharma...announced that the drug registration application for the innovative small molecule CDK4/6 inhibitor Fovinaciclib Citrate Capsules (project code: FCN-437c, hereinafter referred to as 'the new drug') developed by its holding subsidiary Jinzhou Aohong Pharmaceutical Co., Ltd. ('Aohong Pharmaceutical') was recently accepted by the National Medical Products Administration (hereinafter referred to as 'the National Medical Products Administration'). The application is for the treatment of locally advanced or metastatic breast cancer that is hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative, and should be used in combination with aromatase inhibitors as the initial endocrine treatment for premenopausal, postmenopausal, and perimenopausal female breast cancer patients."

China filing • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Fosun Pharma’s (02196.HK) drug registration application for new drug for the treatment of breast cancer has been accepted in the Mainland [Google translation] (Yahoo News) - "Fosun Pharma...announced that its controlled subsidiary Aohong Pharmaceutical has approved FCN-437c capsules combined with fulvestrant for the treatment of hormone receptor (HR) disease that has progressed after previous endocrine therapy) - positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer drug registration application was recently accepted by the State Food and Drug Administration."

Non-US regulatory • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Safety and pharmacokinetics of FCN-437c, a novel cyclin-dependent kinase 4/6 inhibitor, in Chinese patients with hepatic impairment. (PubMed, Invest New Drugs) - P1 | "Thus, no dose adjustment is needed for patients with mild hepatic impairment, but a reduced dose may be necessary for those with moderate hepatic impairment. Trial Registration: www.clinicaltrials.gov identifier NCT06620731 (retrospectively registered)."

Journal • PK/PD data • Breast Cancer • Hepatology • Oncology • Solid Tumor

Pharmacokinetics, mass balance, and metabolism of [14C]FCN-437c, a selective and potent CDK4/6 inhibitor in humans. (PubMed, Cancer Chemother Pharmacol) - "Additionally, 4 phase II metabolites were identified, including two glucuronides, one glutathione conjugate, and one cysteine conjugate. The study provides insights into the metabolic stability and clearance mechanisms of FCN-437c in human, which are essential for its further clinical development and dosing regimens."

Journal • PK/PD data

Clinical Trial of FCN-437c Capsule in Patients With Hepatic Insufficiency (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Ahon Pharmaceutical Co., Ltd.

New P1 trial • Hepatitis C • Liver Failure

No QTc prolongation with CDK 4/6 inhibitor FCN-437c: results of a concentration-QTc analysis from a dedicated study in adult healthy subjects. (PubMed, Front Pharmacol) - P1 | "It is concluded that FCN-437c has low risk of prolonging the QT interval at therapeutic dose. https://clinicaltrials.gov/study/NCT06290466?term=NCT06290466&rank=1, identifier [NCT06290466]."

Journal • Breast Cancer • Cardiovascular • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Clinical Study on Pharmacokinetics of FCN-437c Capsule and Its Effect on QT Interval in Healthy Subjects (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Ahon Pharmaceutical Co., Ltd.

New P1 trial • Breast Cancer • Oncology • Solid Tumor

Phase 2 study of the CDK4/6 inhibitor FCN-437c in combination with Fulvestrant or Letrozole and Goserelin in patients with HR+, HER2– advanced breast cancer (SABCS 2022) - P2, P3 | "FCN-437c in combination with fulvestrant or letrozole + goserelin demonstrates antitumor activity and safety and is well tolerated in pts with HR+, HER2– ABC. This combination therapy will be further investigated in 2 ongoing Phase 3 trials (NCT05438810 and NCT05439499)."

Clinical • Combination therapy • P2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

The CDK4/6 inhibitor FCN-437c plus letrozole for the treatment of HR+/HER2– advanced breast cancer: Updated results from a phase 1b study. (ASCO 2022) - P1/2 | "FCN-437c plus letrozole was well tolerated and demonstrated antitumor activity in patients with previously untreated HR+/HER2– ABC. FCN-437c in combination with NSAI as the first-line treatment for HR+/HER2– ABC will be further investigated in a phase 3 trial."

P1 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • CDK1 • ER • HER-2

A Phase I Dose-Escalation and Dose-Expansion Study of FCN-437c, a Novel CDK4/6 Inhibitor, in Patients with Advanced Solid Tumors. (PubMed, Cancers (Basel)) - "In conclusion, FCN-437c was well tolerated with encouraging signs of antitumor activity and disease control. Further exploration of FCN-437c in aSTs is warranted."

Journal • P1 data • Breast Cancer • Hematological Disorders • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDK4 • KRAS

This is a Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study Evaluating the Efficacy and Safety of FCN-437c in Combination With Fluvestrant ± Goseraline Versus Placebo Combined With Fulvestrant ± Goserelin in Women With HR+ and HER2- Advanced Breast Cancer. (clinicaltrials.gov) - P3 | N=312 | Recruiting | Sponsor: Ahon Pharmaceutical Co., Ltd. | Trial completion date: May 2023 ➔ May 2024 | Initiation date: Jan 2021 ➔ Jan 2022 | Trial primary completion date: Feb 2023 ➔ Feb 2024

Combination therapy • Trial completion date • Trial initiation date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR

This is a Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study Evaluating the Efficacy and Safety of FCN-437c in Combination With Fluvestrant ± Goseraline Versus Placebo Combined With Fulvestrant ± Goserelin in Women With HR+ and HER2- Advanced Breast Cancer. (clinicaltrials.gov) - P3 | N=312 | Recruiting | Sponsor: Ahon Pharmaceutical Co., Ltd.

Combination therapy • New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR

This is a Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study Evaluating the Efficacy and Safety of FCN-437c Versus Placebo in Combination With Letrozole or Anastrozole ± Goserelin in Women With HR+ and HER2- Advanced Breast Cancer. (clinicaltrials.gov) - P3 | N=434 | Recruiting | Sponsor: Ahon Pharmaceutical Co., Ltd.

Combination therapy • New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR

FCN-437c-001: Study of FCN-437c in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Fochon Pharmaceuticals, Ltd. | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS

[VIRTUAL] Phase I dose-escalation and dose-expansion trial of CDK4/6 inhibitor FCN-437c in Chinese female patients with ER+HER2- advanced breast cancer (ABC) (AACR 2021) - "To date, three orally bioavailable CDK4/6 inhibitors, palbociclib, ribociclib and abemaciclib, have been approved for the treatment of ER+HER2- ABC in combination with AI/Fulvestrant or as monotherapy. FCN-437c has established an acceptable safety profile and the toxicities were generally tolerable and manageable. A phase II trial of FCN-437c is now ongoing in combination with Letrozole or Fulvestrant in patients with ER+HER2- ABC, both in treatment naïve and relapse/refractory settings at 200 mg dose level."

Clinical • P1 data • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

FCN-437c-001: Study of FCN-437c in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=22; Active, not recruiting; Sponsor: Fochon Pharmaceuticals, Ltd.; Recruiting ➔ Active, not recruiting; N=36 ➔ 22; Trial completion date: Mar 2023 ➔ Dec 2021; Trial primary completion date: Mar 2021 ➔ Dec 2021

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS

Study of Efficacy, Safety, and Pharmacokinetics of FCN-437c in Combination With Fulvestrant or Letrozole+Goserelin (clinicaltrials.gov) - P2; N=70; Recruiting; Sponsor: Ahon Pharmaceutical Co., Ltd.

New P2 trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Phase 1a study of the CDK4/6 inhibitor, FCN-437c, in Chinese patients with HR + /HER2- advanced breast cancer. (PubMed, Invest New Drugs) - P1/2 | "Conclusions These results established an acceptable safety profile for FCN-437c in patients with advanced BC, and there were no unexpected signals relative to other CDK4/6 inhibitors. (NCT04488107; July 13, 2020)."

Clinical • Journal • P1 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • HER-2

Study of FCN-437c in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Fochon Pharmaceuticals, Ltd.; Trial completion date: Sep 2022 ➔ Mar 2023; Trial primary completion date: Sep 2020 ➔ Mar 2021

Trial completion date • Trial primary completion date • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS

Safety, Tolerability, Pharmacokinetics and Antitumor Activity of FCN-437c (clinicaltrials.gov) - P1/2; N=78; Recruiting; Sponsor: Ahon Pharmaceutical Co., Ltd.

Clinical • Combination therapy • New P1/2 trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

Study of FCN-437c in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Fochon Pharmaceuticals, Ltd.; Trial completion date: Jun 2020 ➔ Sep 2022; Trial primary completion date: May 2020 ➔ Sep 2020

Clinical • Trial completion date • Trial primary completion date

Study of FCN-437c in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=36; Recruiting; Sponsor: Fochon Pharmaceuticals, Ltd.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open