Delving into the Latest Updates on FF-21101-Y-90 with Synapse

Overview

Basic Info

Drug Type

Radiolabeled antibody, Therapeutic radiopharmaceuticals

Synonyms

+ [3]

Target

CDH3

Action

inhibitors

Mechanism

CDH3 inhibitors(Cadherin 3 inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Solid tumor

Inactive Indication

Advanced cancerAdvanced Malignant Solid NeoplasmBile Duct Neoplasms+ [6]

Originator Organization

FUJIFILM Holdings Corp.

Active Organization

PDRadiopharma, Inc.

Inactive Organization

FUJIFILM Pharmaceuticals USA, Inc.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

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P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human-mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (¹¹¹In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(¹¹¹In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of ¹¹¹In- and yttrium-90 (⁹⁰Y)-FF-21101 for targeted radioimmunotherapy in humans. Whole-body planar and SPECT imaging were performed at 0, 2, 24, 48, 72, 96, and 120 h post-injection, using a dual-head gamma camera. Volumes of interest of identifiable source organs of radioactivity were defined on aligned reference CT and serial SPECT images. Organs with the highest estimated dose values (mSv/MBq) for FF-21101(¹¹¹In) were the lungs (0.840), spleen (0.816), liver (0.751), kidneys (0.629), and heart wall (0.451); and for FF-21101(⁹⁰Y) dose values were: lungs (10.49), spleen (8.21), kidneys (5.92), liver (5.46), and heart wall (2.61). FF-21101(¹¹¹In) exhibits favorable biodistribution in cynomolgus macaques and estimated human dosimetric characteristics. Data obtained in this study were used to support the filing of an investigational new drug application with the FDA for a Phase I clinical trial.

01 Feb 2021·Journal of Nuclear Medicine

Preclinical Characterization of the Radioimmunoconjugate¹¹¹In or⁹⁰Y-FF-21101 Against a P-Cadherin–Expressing Tumor in a Mouse Xenograft Model and a Nonhuman Primate

Article

Author: Funase, Yuichi ; Kajita, Masamichi ; Tokura, Masahiko ; Uehara, Tomoya ; Kitano, Michi ; Saito, Yasutaka ; Nakamura, Eri ; Oshikiri, Shinobu ; Hino, Akihiro

P-cadherin is overexpressed in various cancers and can be a target for radioimmunotherapy. We investigated the preclinical pharmacokinetics and pharmacology of FF-21101, an ¹¹¹In- or ⁹⁰Y-conjugated monoclonal antibody against P-cadherin, to evaluate its clinical applications. Methods: The radiochemical purity, binding affinity, and in vitro serum stability of ¹¹¹In or ⁹⁰Y-labeled FF-21101 were evaluated. The pharmacokinetics of ¹¹¹In or ⁹⁰Y-FF-21101 were compared in normal mice. Tumor accumulation after ¹¹¹In-FF-21101 administration was investigated in mice bearing subcutaneous tumors with high (NCI-H1373), moderate (EBC-1), or no (A549) P-cadherin expression. The tumor suppression effect after a single intravenous injection of ⁹⁰Y-FF-21101 was assessed in NCI-H1373 and EBC-1 mouse xenograft models. The relationship between antibody dose and tumor accumulation was investigated in the NCI-H1373 mouse xenograft model. The absorbed radiation dose in humans after injection of ⁹⁰Y-FF-21101 was estimated using γ-camera images of cynomolgus monkeys. Results: The radiochemical purities of ¹¹¹In- and ⁹⁰Y-FF-21101 were 98.2% ± 2.5% (n = 9) and 99.3% ± 0.6% (n = 5), respectively. The dissociation constants were 1.083 nM for ¹¹¹In-FF-21101 and 1.367 nM for ⁹⁰Y-FF-21101. Both ¹¹¹In- and ⁹⁰Y-FF-21101 were stable in human serum after 96 h of incubation and exhibited similar pharmacokinetics in normal mice. The tumor accumulation of ¹¹¹In-FF-21101 was closely related to the intensity of P-cadherin expression in the cells. ⁹⁰Y-FF-21101 showed significant tumor growth inhibition, indicating that NCI-H1373 and EBC-1 recurrence was not observed after intravenous administration of 3.7 and 7.4 MBq, respectively of ⁹⁰Y-FF-21101 per animal. Tumor uptake in the mouse xenograft model and estimated absorbed radiation doses in the spleen of monkeys decreased with increasing antibody doses of ¹¹¹In-FF-21101. Conversely, the estimated absorbed radiation dose in the red marrow increased with increasing antibody dose. An antibody dose of 4.8 mg/m² was considered appropriate for humans, on the basis of efficacy and safety. The maximum tolerated administered activity of ⁹⁰Y-FF-21101 was estimated to be 2,886 MBq/human. Conclusion: FF-21101 radioimmunotherapy exhibited high antitumor affinity and antitumor efficacy in mouse xenograft models. Extrapolation of the pharmacokinetics in monkeys to humans suggests the potential for clinical application of FF-21101 for treating P-cadherin-expressing tumor.

15 Nov 2020·Clinical Cancer ResearchQ1 · MEDICINE

Phase I Study of P-cadherin–targeted Radioimmunotherapy with 90Y-FF-21101 Monoclonal Antibody in Solid Tumors

Q1 · MEDICINE

Article

Author: Meric-Bernstam, Funda ; Hong, David S. ; Nakamura, Eri ; Ravizzini, Gregory ; Liu, Holly ; Le, Dao ; Subach, Ruth Ann ; Wages, David ; Funase, Yuichi ; Satoh, Hirokazu ; Madden, Timothy ; Suzuki, Takeaki ; Kajita, Masamichi ; Santos, Elmer ; Matsushima, Satoshi ; Pant, Shubham ; Johansen, Mary ; Erwin, William ; Gonzalez, Jose ; Subbiah, Vivek ; Macapinlac, Homer ; Mawlawi, Osama ; Wheeler, Catherine ; Gonzalez-Lepera, Carlos ; Nomura, Fumiko ; McCoy, Asa ; Matsuura, Tadashi ; Roszik, Jason

AbstractPurpose:90Y-FF-21101 is an Yttrium-90–conjugated, chimeric mAb that is highly specific for binding to human placental (P)-cadherin, a cell-to-cell adhesion molecule overexpressed and associated with cancer invasion and metastatic dissemination in many cancer types. We report the clinical activity of 90Y-FF-21101 in a first-in-human phase I study in patients with advanced solid tumors.Patients and Methods:The safety and efficacy of 90Y-FF-21101 were evaluated in a phase I 3+3 dose-escalation study in patients with advanced solid tumors (n = 15) over a dose range of 5–25 mCi/m2. Dosimetry using 111In-FF-21101 was performed 1 week prior to assess radiation doses to critical organs. Patients who demonstrated clinical benefit received repeated 90Y-FF-21101 administration every 4 months.Results:111In-FF-21101 uptake was observed primarily in the spleen, kidneys, testes, lungs, and liver, with tumor uptake observed in the majority of patients. Organ dose estimates for all patients were below applicable limits. P-cadherin expression H-scores ranged from 0 to 242 with 40% of samples exhibiting scores ≥100. FF-21101 protein pharmacokinetics were linear with increasing antibody dose, and the mean half-life was 69.7 (±12.1) hours. Radioactivity clearance paralleled antibody clearance. A complete clinical response was observed in a patient with clear cell ovarian carcinoma, correlating with a high tumor P-cadherin expression. Stable disease was observed in a variety of other tumor types, without dose-limiting toxicity.Conclusions:The favorable safety profile and initial antitumor activity observed for 90Y-FF-21101 warrant further evaluation of this radioimmunotherapeutic (RIT) approach and provide initial clinical data supporting P-cadherin as a potential target for cancer treatment.

100 Deals associated with FF-21101-Y-90

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 1	Japan	PDRadiopharma, Inc.	-
Advanced cancer	Preclinical	United States	FUJIFILM Pharmaceuticals USA, Inc.	01 Jan 2016
Advanced Malignant Solid Neoplasm	Preclinical	United States	FUJIFILM Pharmaceuticals USA, Inc.	01 Jan 2016
Bile Duct Neoplasms	Preclinical	United States	FUJIFILM Pharmaceuticals USA, Inc.	01 Jan 2016
Colorectal Cancer	Preclinical	United States	FUJIFILM Pharmaceuticals USA, Inc.	01 Jan 2016
Fallopian Tube Carcinoma	Preclinical	United States	FUJIFILM Pharmaceuticals USA, Inc.	01 Jan 2016
Gallbladder Carcinoma	Preclinical	United States	FUJIFILM Pharmaceuticals USA, Inc.	01 Jan 2016
Pancreatic Cancer	Preclinical	United States	FUJIFILM Pharmaceuticals USA, Inc.	01 Jan 2016
Squamous Cell Carcinoma of Head and Neck	Preclinical	United States	FUJIFILM Pharmaceuticals USA, Inc.	01 Jan 2016
Triple Negative Breast Cancer	Preclinical	United States	FUJIFILM Pharmaceuticals USA, Inc.	01 Jan 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AACR2018 Manual	Not Applicable	Advanced Malignant Solid Neoplasm	14	FF-21101(90Y)	(tlgseszcqc) = bybmgwxhid qxicmsempi (ekdcptfwxu ) View more	Positive	01 Jul 2018

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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