A Phase 1 Trial for Evaluation of Safety and 177Lu Radiation Dosimetry of CTT1403: A Peptidomimetic Inhibitor of Prostate Specific Membrane Antigen, in Metastatic Castration Resistant Prostate Cancer (mCRPC)

The purpose of this study is to find the highest dose level of study drug, CTT1403, that can be safely administered to patients with metastatic castration resistant prostate cancer (mCRPC).

Start Date01 Apr 2019

Sponsor / Collaborator

Cancer Targeted Technology LLC

[+2]

100 Clinical Results associated with CTT-1403

100 Translational Medicine associated with CTT-1403

100 Patents (Medical) associated with CTT-1403

Literatures (Medical) associated with CTT-1403

24 Jul 2026·CURRENT MEDICINAL CHEMISTRY

Radionuclide Therapy of Prostate Cancer Using PSMA Ligands with a 4-Phenylbutyric Acid-Derived Albumin Binder: Recent Chemical and Clinical Advances

Article

Author: Rubira, Lea ; Fersing, Cyril ; Renaud, Stephane C. ; Vanney, Johanne ; Torchio, Jade

Abstract::

Radioligand therapy (RLT) targeting the prostate-specific membrane antigen (PSMA) has become a key treatment modality for metastatic castration-resistant prostate cancer. However, the rapid clearance and suboptimal tumor uptake of current smallmolecule PSMA ligands limit their therapeutic index. Incorporating reversible albuminbinding moieties (ABM), particularly 4-phenylbutyric acid (PBA)-derived groups, has emerged as a powerful strategy to modulate pharmacokinetics by prolonging systemic circulation, enhancing tumor uptake, and improving radiation dose delivery. This review summarizes the chemical and translational advances of PSMA-targeting radiopharmaceuticals integrating PBA-type ABM. It details structure-activity relationships governing albumin affinity and linker design across all major chemical series. Emphasis is placed on the most clinically advanced candidates, i.e. PSMA-Trillium, HTK03170, Ludotadipep, P17-088, and CTT1403, highlighting their pharmacokinetics, tumor targeting, safety profiles, and early clinical outcomes. Key determinants of in vivo performance, including affinity for albumin and PSMA, polarity and length of linker elements, are examined in the context of tumor-to-kidney dose ratios and therapeutic efficacy. Collectively, PBA-derived ABM have proven highly effective but require careful tuning, as excessive albumin binding could lead to prolonged hematologic exposure and kidney irradiation, whereas insufficient affinity reduces therapeutic gains. The most successful ligands achieve a balanced interplay between albumin binding, PSMA affinity, and controlled renal clearance. As next-generation α- and β-emitters enter clinical development, optimized ABM-containing radiopharmaceuticals are expected to deliver higher tumor doses with improved safety, supporting their growing role in precision therapy for advanced prostate cancer.

01 Mar 2026·NUCLEAR MEDICINE AND BIOLOGY

Development of an automated one-step radiolabeling procedure for a PSMA-targeted radiotherapeutic for prostate cancer

Article

Author: Ocak, Meltem ; Ho, Khanh-Van ; Ling, Xiaoxi ; Langton-Webster, Beatrice C ; Simón, Jaime ; Berkman, Clifford E ; Fulton, Melody D ; Bomba, Hunter N ; Anderson, Carolyn J ; Pun, Michael ; Carroll, Valerie N ; Sikligar, Kanishka

BACKGROUND:

CTT1403 (¹⁷⁷Lu-CTT2001), an irreversible phosphoramidate PSMA inhibitor developed by Cancer Targeted Technology, was initially synthesized using a two-step radiolabeling method and has previously been evaluated in first-in-human studies. This two-step approach protected the phosphoramidate pharmacophore-containing a temperature- and pH-labile PN bond-from the harsh conditions required for lutetium-177 (¹⁷⁷Lu) chelation. Although the final chemical structure of CTT1403 is identical regardless of the radiolabeling route, it was not clear that CTT2001 could tolerate one-step labeling conditions while preserving PSMA-binding integrity. Therefore, the aim of the study was to develop, optimize, and automate a one-step radiolabeling method for CTT1403 and to confirm that the resulting product is biologically equivalent and exhibits comparable in vitro and in vivo behavior to CTT1403 produced by the original two-step process.

METHODS:

CTT2001 was synthesized and radiolabeled with ¹⁷⁷Lu using an optimized one-step procedure that was subsequently automated on a Trasis AllinOne synthesizer. Radiochemical purity, stability, cellular uptake/internalization, and biodistribution in PC3-PIP tumor-bearing mice were evaluated.

RESULTS:

CTT1403 synthesized via the one-step method demonstrated cellular uptake and internalization in PC3-PIP cells, as well as in vivo biodistribution in PC3-PIP tumor-bearing mice, that were comparable to those of the two-step-labeled product. The one-step procedure was successfully automated on the Trasis All-in-One synthesizer, producing CTT1403 with a radiochemical yield of 86.5 ± 4.27% (n = 3), a molar activity of 30.3 ± 1.11 MBq/nmol, and a radiochemical purity of 97.6 ± 0.80% (n = 3) in a total synthesis time of 38 min. The final product remained stable for at least 24 h at -4 °C and -20 °C.

CONCLUSIONS:

The one-step radiolabeling method yields CTT1403 that is biologically equivalent to the two-step product and can be reliably produced using fully automated synthesis. This streamlined, efficient, and reproducible approach supports routine clinical manufacturing of CTT1403.

01 Apr 2020·Molecular imaging and biologyQ3 · MEDICINE

Preclinical Dosimetry, Imaging, and Targeted Radionuclide Therapy Studies of Lu-177-Labeled Albumin-Binding, PSMA-Targeted CTT1403

Q3 · MEDICINE

Article

Author: Geruntho, Jonathan J ; Anderson, Carolyn J ; Rigatti, Lora H ; Salamacha, Nathan ; Wu, Yijen ; Laymon, Charles M ; Ling, Xiaoxi ; Windish, Hillarie P ; Kurland, Brenda F ; Shen, Ding ; Choy, Cindy J ; Langton-Webster, Beatrice ; Berkman, Clifford E ; Latoche, Joseph D

PURPOSE:

Prostate-specific membrane antigen (PSMA) continues to be the hallmark biomarker for prostate cancer as it is expressed on nearly all prostatic tumors. In addition, increased PSMA expression correlates with castration resistance and progression to the metastatic stage of the disease. Recently, we combined both an albumin-binding motif and an irreversible PSMA inhibitor to develop the novel PSMA-targeted radiotherapeutic agent, CTT1403. This molecule was novel in the field of PSMA-targeted agents as its key motifs resulted in extended blood circulation time and tumor uptake, rapid and extensive internalization into PSMA+ cells, and promising therapeutic efficacy. The objective of this study was to perform IND-enabling translational studies on CTT1403 in rodent models.

PROCEDURES:

A dose optimization study was performed in PC3-PIP (PSMA+) tumor-bearing mice. Treatment groups were randomly selected to receive one to three 14-MBq injections of CTT1403. Control groups included (1) saline, (2) non-radioactive [¹⁷⁵Lu]CTT1403, or (3) two injections of 14 MBq CTT1751, a Lu-177-labeled non-targeted albumin-binding moiety. Tumor growth was monitored up to 120 days. Small-animal single photon emission tomography/X-ray computed tomography imaging was performed with CTT1403 and CTT1751 in PC3-PIP tumor-bearing mice to visualize infiltration of the Lu-177-labeled agent into the tumor. In preparation for a first-in-human study, human absorbed doses were estimated based on rat biodistribution out to 5 weeks to determine a safe CTT1403 therapy dose in humans.

RESULTS:

Two to 3 injections of 14 MBq CTT1403 yielded significant tumor growth inhibition and increased survival compared with all control groups and mice receiving 1 injection of 14 MBq CTT1403. Five of 12 mice receiving 2 or 3 injections of CTT1403 survived to the 120-day post-treatment study endpoint. Dosimetry identified the kidneys as the dose-limiting organ, with an equivalent dose of 5.18 mSv/MBq, resulting in a planned maximum dose of 4.4 GBq for phase 1 clinical trials.

CONCLUSIONS:

The preclinical efficacy and dosimetry of CTT1403 suggest that this agent has significant potential to be safe and effective in humans.

News (Medical) associated with CTT-1403

07 Aug 2020

·www.cancertargetedtechnology.com

NIH grants $1.44M to Cancer Targeted Technology to Support the Ongoing Prostate Cancer Clinical Trial of a Promising New Radiotherapeutic, CTT1403

Published: August 07, 2020 09:30 AM Eastern Daylight Time SEATTLE--(BUSINESS WIRE) Cancer Targeted Technology (CTT), a privately-held Seattle-based biotechnology company, announced that the NIH awarded CTT $1.44M on the second year of a competitive Small Business Innovation Research (SBIR) Phase IIB grant. The three year grant commenced in 2019 and totals $3.3M and this second year of funding supports the current CTT1403 clinical trial. The clinical trial, conducted at University of California, San Francisco with Dr. Rahul Aggarwal as Principal Investigator, is a 30-40 patient dose escalation/expansion trial in men with advanced castration-resistant prostate cancer. The trial is designed to show safety and efficacy of CTT1403 and is halfway through the initial dose escalation phase. To date there have been no safety issues with the drug and the pharmacokinetic data support the longer circulation time of CTT1403 in the blood stream as compared to other PSMA agents currently in clinical trials. "These PSMA-targeted agents are already transforming how prostate cancer is diagnosed and treated and we are very pleased that the NIH continues to support the development of these exciting new agents. CTT1403, with its longer circulating time and better tumor targeting characteristics, offers distinct advantages in this treatment arena providing the patient with cost and treatment benefits,” commented Dr. Beatrice Langton-Webster, CTT’s CEO and Principal Investigator on the grant. The unique chemical structure for CTT1403 was conceived of by Dr. Cliff Berkman, Professor at Washington State University (WSU). CTT1403 targets Prostate Specific Membrane Antigen (PSMA) which is over-expressed on prostate cancer. Two features make CTT1403 unlike other PSMA-targeted drugs currently in development: 1) Due to a unique core scaffold, CTT’s molecules bind irreversibly to PSMA and this distinctive mode of binding enables rapid uptake of the drug within the tumor; and 2) CTT1403 is engineered to increase the circulation time of the drug in the body which further substantially increases the dose of drug that accumulates at the tumor sites. CTT1403 is labeled with the radionuclide Lutetium-177 and once delivered to the tumor, the radionuclide acts to destroy the tumor cells. CTT completed two clinical trials at UCSF with CTT1057, the companion PET diagnostic imaging agent to CTT1403, with excellent safety and imaging results for both prostate cancer and renal cell carcinoma. CTT1057 is undergoing further development for prostate cancer by CTT’s licensing partner AAA/Novartis. CTT1057 and CTT1403 serve as a theranostic pair to both diagnose and treat solid tumors that express PSMA, and are being used together in the current clinical trial. More information on the trial can be found at clinicaltrials.gov. View source version on businesswire.com https://www.businesswire.com/news/home/20200807005027/en Contacts Cancer Targeted Technology Dr. Beatrice Langton-Webster bealw@cancertargetedtechnology.com

Phase 2

06 Nov 2018

·www.cancertargetedtechnology.com

Cancer Targeted Technology Files Investigational New Drug Application for CTT1403, a Novel Radiotherapeutic Drug for Prostate Cancer

November 06, 2018 09:30 AM Eastern Standard Time SEATTLE--(BUSINESS WIRE)--Cancer Targeted Technology (CTT), a privately-held Seattle-based biotechnology company, announced today that it filed an Investigational New Drug Application (IND) with the FDA to move forward a radiotherapeutic drug, CTT1403, into human clinical trials for prostate cancer. CTT1403 is a peptidomimetic drug that targets Prostate Specific Membrane Antigen (PSMA). PSMA is over-expressed on prostate cancer and this expression increases as the cancer metastasizes and becomes hormone-resistant. Unlike other drugs, CTT’s molecules bind irreversibly to PSMA. This distinctive mode of binding enhances uptake and results in rapid and extensive internalization of these drugs by tumor cells, leading to increased uptake within the tumor. CTT1403 is labeled with the radionuclide 177-Lutetium and, unlike other PSMA-targeted drugs in clinical development, contains a unique albumin binding component. The albumin binding moiety on CTT1403 acts to increase the circulation of the drug in the body and further substantially increases the dose of drug that accumulates at the tumor sites. Once targeted to the tumor, the radionuclide on CTT1403 leads to tumor cell destruction. CTT1403 has shown excellent safety results to date in animal studies and CTT1403 treatment results in prolonged survival of animals with prostate cancer tumors. "We are very excited with the potential for CTT1403 to make a difference in men with advanced stage prostate cancer. This is a highly innovative molecule that combines excellent PSMA-targeting characteristics, already proven effective in prostate cancer, with the ability to enhance circulation time allowing for greater anti-tumor effects,” stated Dr. Beatrice Langton-Webster, CTT’s CEO and Principal Investigator for the clinical program. The unique chemical structure for CTT1403 was designed by Dr. Cliff Berkman, Professor of Chemistry at Washington State University (WSU) and consultant to CTT as its Chief Scientific Officer. The work to discover and progress CTT1403 through preclinical development to IND was funded by a $2.3M Small Business Innovation Research contract from the NIH. CTT recently completed clinical trials of CTT1057, the companion PET diagnostic to CTT1403, with excellent safety and imaging results. CTT1057 is undergoing further development and commercialization by CTT’s licensing partner AAA/Novartis. CTT1057 and CTT1403 can act as a theranostic pair to both diagnose and treat prostate cancer. Phase I clinical trials for CTT1403 are expected to start January, 2019. Contacts Cancer Targeted Technology Dr. Beatrice Langton-Webster bealw@cancertargetedtechnology.com

INDPhase 1

23 Oct 2018

·www.cancertargetedtechnology.com

Cancer Targeted Technology Receives an SBIR Grant and Announces Expansion of Its Pipeline

Cancer Targeted Technology Receives an SBIR Grant and Announces Expansion of Its Pipeline October 23, 2018 09:00 AM Eastern Daylight Time SEATTLE--(BUSINESS WIRE)--Cancer Targeted Technology (CTT), a privately-held Seattle-based biotechnology company focusing on small molecules that bind to pivotal enzyme cancer targets, announced that it received a Small Business Innovation Research (SBIR) grant to develop CTT1700, a unique prodrug targeted at men with prostate cancer that express Prostate Specific Membrane Antigen (PSMA). PSMA is over-expressed on prostate cancer and this expression increases as the cancer metastasizes and becomes hormone-resistant. Unlike other agents targeting PSMA in development, CTT’s agents bind irreversibly to PSMA. This distinctive mode of binding enhances uptake and results in rapid and extensive internalization by tumor cells, leading to increased accumulation of the drugs within the tumor. CTT1700 relies on a novel drug-release technology that is triggered by the pH inside of the cell to selectively release the chemotherapy once inside the tumor cells. As a result, toxic side effects to bystander or normal cells are reduced or eliminated. "This new chemotherapeutic drug, CTT1700, like all of CTT’s drugs, are based on the same versatile modular PSMA-targeting platform. This platform allows for rapid development of various PSMA-targeted agents by conveniently swapping out the payload,” commented Dr. Cliff Berkman, Professor of Chemistry at Washington State University (WSU) and consultant to CTT as its Chief Scientific Officer. Dr. Berkman and WSU were instrumental in developing the new drug-release technology for CTT1700 that was licensed to CTT in 2017. CTT’s pipeline now includes three important drugs targeting cancers that express PSMA. CTT1057 is a diagnostic PET imaging agent capable of rapidly and sensitively detecting metastatic disease in prostate cancer patients. CTT1057 demonstrated excellent results in Phase 1 clinical trials completed in 2017 and the drug was licensed to AAA/Novartis in January, 2018. The second agent, CTT1403, is a radiotherapeutic drug that delivers a therapeutic dose of 177-lutetium to tumor cells expressing PSMA. CTT1403, unlike other PSMA-targeted drugs, includes an albumin binding component that imparts a long circulation time allowing for more of the drug to get to the tumor cells. CTT1403 is expected to start Phase I clinical trials in prostate cancer patients in early 2019. CTT1700, currently in preclinical development, is the third agent in CTT’s pipeline and would be the first drug to use binding to the PSMA biomarker to target chemotherapy to prostate cancer. Contacts Cancer Targeted Technology Dr. Beatrice Langton-Webster bealw@cancertargetedtechnology.com

Phase 1Clinical Result

100 Deals associated with CTT-1403

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic castration-resistant prostate cancer	Phase 1	United States	Cancer Targeted Technology LLC	01 Apr 2019
Prostatic Cancer	Phase 1	United States	Cancer Targeted Technology LLC	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03822871 (CTgov)	Phase 1	Metastatic castration-resistant prostate cancer	17	CTT1043 (0.75 GBq Cohort)	guxnhaboow = nvutkjvgpv ierbxyvosr (yxccofmzmu, qvsyhxpelw - llmcojjyrr) View more	-	21 Mar 2024
				CTT1043 (1.5 GBq Cohort)	guxnhaboow = sxhvsunvwz ierbxyvosr (yxccofmzmu, gummplkcya - isuarqhgyj) View more
CTT1403 (SNMMI2020)	Phase 1	PSMA-Positive Tumor prostate specific membrane antigen	6	CTT1403 0.75 GBq	gpvncaqcmr(xteemfzjal) = mhwpbdcrui vdwssdyiwc (ndbrzzbscg, 0.36) View more	Positive	15 May 2020
				CTT1403 1.5 GBq	gpvncaqcmr(xteemfzjal) = kpvgilisue vdwssdyiwc (ndbrzzbscg, 0.36) View more

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