Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Prostatic Neoplasms

Adenocarcinoma

Stomach Neoplasms

Recurrence

Squamous Cell Carcinoma of Head and Neck

Sarcoma

Sarcoma, Ewing

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Neoplasms, Connective and Soft Tissue

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Head and Neck Neoplasms

Stomach Cancer

Soft Tissue Sarcoma

Ewing Sarcoma

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Radiopharmaceuticals

Pancreatin

\[225Ac\]-FPI-2059 is a targeted alpha therapeutic that consists of an NTSR1-targeting small molecule that is linked to Ac-225, an alpha particle emitting radionuclide. Participants will be dosed through IV administration every 56 days up to four cycles. The dose depends on cohort assignment.

In the Dose Expansion arm, \[225Ac\]-FPI-2059 will be administered at the RP2D as determined in Phase 1 Dose Escalation.

[225]-FPI-2059

\[111In\]-FPI-2058 is an imaging agent that consists of an NTSR1-targeting small molecule linked to In-111.Participants will receive \[111In\]-FPI-2058 by IV Injection for imaging once during screening period. The dose is consistent across cohorts.

[111In]-FPI-2058

Clinical Trials Fusion Pharmaceuticals

Luke Nordquist, Dr.

Tony Romero

Joanne Schindler, MD, DVM

This is a first-in-human Phase 1 clinical trial designed to investigate the safety, tolerability, pharmacokinetics, and biodistribution of \[225Ac\]-FPI-2059 and \[111In\]-FPI-2058 in participants with neurotensin receptor 1 (NTSR1)-expressing solid tumours.

This is a first-in-human, Phase 1, non-randomized, multi-centre, open-label clinical trial designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of \[225Ac\]-FPI-2059 and \[111In\]-FPI-2058, as well as the pharmacodynamics and preliminary anti-tumour activity of \[225Ac\]-FPI-2059 in participants with neurotensin receptor 1 (NTSR1)-expressing advanced, metastatic and/or recurrent solid tumours.

The study will employ a 3+3 dose escalation design to identify the recommended phase 2 dose (RP2D) and regimen of \[225Ac\]-FPI-2059 administered intravenously every 56 days.

After the RP2D for \[225Ac\]-FPI-2059 is determined, enrolment will continue into an expansion cohort, to confirm the safety and tolerability of the RP2D, as well as to identify any preliminary evidence of efficacy in selected NTSR1-expressing tumour types.

A Study of [225Ac]-FPI-2059 in Adult Participants With Solid Tumours

A Phase 1 Study of [225Ac]-FPI-2059 in Adult Participants With NTSR1-Expressing Advanced, Metastatic and/or Recurrent Solid Tumours

Fusion Pharmaceuticals Inc.

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Disease Progression

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Somatostatin

Dose escalation study to assess the safety and determine the recommended phase II dose, based on time-to-event Bayesian optimal interval design, with a target toxicity rate of 30%. Three dose levels are planned to be evaluated: 5 MBq (starting dose), 7.5 MBq and 10 MBq (maximum dose allowed). The cohort size will be 3, with a maximum of 10 participants within a same dose level, and a maximum of 18 evaluable participants in total. Participants are planned to receive two cycles of intravenous infusion of 225Ac-DOTATATE every 6 weeks (Q6W). Each dose escalation and potential de-escalation step will be decided based on the dose-limiting toxicities (DLT) rate observed during the study treatment period (84 days following the first infusion), in the current dose cohort.

Two intravenous infusions every 6 weeks (Q6W)

225Ac-DOTATATE

Wendy Delbart, PhD

This study aims to determine the safety and the recommended phase II dose of RYZ101 (actinium-225 labelled DOTA-octreotate (225Ac-DOTATATE)) in participants with refractory and relapsing multiple myeloma (MM) that have received at least 3 prior lines of myeloma therapy. Participants will be selected based on somatostatin receptor (SSTR) positivity assessed by gallium-68 labelled DOTA-octreotate (68Ga-DOTATATE) PET/CT. The response to 225Ac-DOTATATE therapy will also be assessed in the target study population.

A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients With Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors

Incidence and severity of adverse events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

Rate incidence of dose-limiting toxicities (DLT)

Overall response according to the International Myeloma Working Group (IMWG) response criteria

RayzeBio, Inc.

Jules Bordet Institute

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antibodies

Antibodies, Monoclonal

Antibodies, Bispecific

Immunoglobulins

Mitogens

Chelating Agents

The study conducted in two parts: Part A Dose Exploration and Part B Dose Escalation

FPI-2053 dose exploration to determine the optimal pre-dose administration of FPI-2053 with a fixed dose of \[225Ac\]-FPI-2068.

\[225Ac\]-FPI-2068 dose escalation with the optimal dose of FPI-2053 as determined in Part A.

FPI-2053 is a bispecific antibody that targets EGFR and cMET

FPI-2053

\[111In\]-FPI-2107 is an imaging agent in which indium-111 is conjugated to FPI-2053.

Participants will have a fixed dose of \[111In\]-FPI-2107 followed by imaging scans (with or without pre-administration of FPI-2053).

[111In]-FPI-2107

\[225Ac\]-FPI-2068 is a radiopharmaceutical therapy in which an alpha emitter, actinium-225, is conjugated to FPI-2053.

Participants will be dosed through IV administration every 56 days for up to 3 cycles of the Treatment Period.

[225Ac]-FPI-2068

Clinical Trials Fusion Pharmaceuticals Clinical Operations

David Marcellus

Andrei Iagaru, MD

Aditya Juloori, MD

Veronika Seseri

Heather Jacene, MD

Kristen Harrington

Richard Wahl, MD

John Crandall

Jordi Rodon Ahnert, MD

Yang Lu, MD

Delphine Chen, MD

Heather White

Daniel Juneau, MD

Michel Pavic, MD

Christine Lawson

Éric Turcotte, MD

Lisa Jean-Louis

This is a first-in-human, Phase 1, non-randomized, multicenter, open-label clinical study designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of \[225Ac\]-FPI-2068, \[111In\]-FPI-2107, and FPI-2053 in metastatic and/or recurrent solid tumors (HNSCC, NSCLC, mCRC, PDAC).

The study will be conducted in 2 parts:

Part A: optimization of the FPI-2053 dose (treatment with dose level 1 of \[225Ac\]-FPI-2068 - fixed dose).

Part B: dose escalation of \[225Ac\]-FPI-2068 with optimal FPI-2053. Part B will commence once the optimal dose of FPI-2053 is determined in Part A. The RP2D will be determined from Part B based on all available safety, efficacy, PK, and dosimetry information.

A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

A Phase 1, First-in-human, Multicentre, Open-label, Dose Escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

• Incidence of Adverse Events and evaluation of dosimetry

* For Part A, evaluate the impact of pre-dose administration of FPI-2053 on the radiation dosimetry of \[111In\]-FPI-2107 (whole body, organs, and selected regions of interest)
* Estimate the effect of pre-dose administration of FPI-2053 on the radiation dosimetry of \[225Ac\]-FPI-2068 (whole body, organs, and selected regions of interest)

Determine the RP2D of \[225Ac\]-FPI-2068, given with or without FPI-2053

• Tumour assessments will be based on RECIST v1.1 (Eisenhauer et al, 2009) and will be performed approximately every 8 weeks (± 1 week) after the first \[225Ac\]-FPI-2068 dose, or as clinically indicated.

• Tumor uptake of \[111In\]-FPI-2107 in selected regions of interest on SPECT/CT and/or planar images

• Determine the plasma concentrations and PK parameters of \[111In\]-FPI-2107, and \[225Ac\]-FPI-2068 and the effect of pre-dose administration of FPI-2053 on the plasma concentrations and PK parameters of \[111In\]-FPI-2107.

• Presence of ADA for \[111In\]-FPI-2107, \[225Ac\]-FPI-2068, and FPI-2053

AstraZeneca

Gland and Hormone Related Diseases

Thyroid Neoplasms

Thyroid Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Targeted alpha therapy

Tadashi Watabe, M.D., Ph.D.

Single intravenous administration of TAH-1005 is performed in patients with differentiated thyroid cancer (papillary cancer, follicular cancer) who cannot obtain therapeutic effect with standard treatment or who have difficulty in implementing and continuing standard treatment. The safety, pharmacokinetics, absorbed dose, and efficacy will be evaluated to determine the recommended dose for Phase II clinical trial.

Radioactive iodine (I-131) has long been used clinically for patients with metastatic differentiated thyroid cancer. However, some patients are refractory to repetitive I-131 treatment, despite the targeted regions showing sufficient iodine uptake. In such patients, beta-particle therapy using I-131 is inadequate and another strategy is needed using more effective radionuclide targeting the sodium/iodide symporter (NIS). Astatine (At-211) is receiving increasing attention as an alpha-emitter for targeted radionuclide therapy. At-211 is a halogen element with similar chemical properties to iodine. Alpha particles emitted from At-211 has higher linear energy transfer as compared to beta particles from I-131 and exert a better therapeutic effect by inducing DNA double strand breaks and free radical formation. Thus, targeted alpha therapy using At-211 is highly promising for the treatment of advanced differentiated thyroid cancer.

Targeted Alpha Therapy Using Astatine (At-211) Against Differentiated Thyroid Cancer

Phase I Investigator-initiated Clinical Trial in Patients With Differentiated Thyroid Cancer (Papillary Cancer, Follicular Cancer) by the Targeted Alpha Therapy Drug TAH-1005 ([211At] NaAt) (Alpha-T1 Study)

Type, severity, frequency of occurrence and duration of adverse events

Toxicity is defined as one or more of the following items for which a causal relationship with the investigational drug cannot be ruled out.

1. Grade 3 \* hematological toxicity that lasts for 7 days or more
2. Hematological toxicity of Grade 4 \* or higher regardless of duration
3. Febrile neutropenia regardless of duration
4. Thrombocytopenia with bleeding tendency or requiring platelet transfusion
5. Anemia requiring red blood cell transfusion
6. Neutropenia with infection
7. Non-hematological toxicity of Grade 3 \* or higher that does not improve with symptomatic treatment and lasts for 7 days or longer. However, the following are excluded.

   * Abnormal laboratory test values that are not clinically significant
   * Toxicity that can be controlled to Grade 2 \* or less with maximum supportive care
   * Due to exacerbation of the underlying disease (\*: Grade specified in CTCAE v.5.0J COG version)

Systolic and diastolic blood pressure (mmHg)

Subjective symptoms and medical examination findings

White blood cell count (/μL), red blood cell count (×10\^4/μL), hemoglobin (g/dL), hematocrit (%), platelet count (×10\^4/μL)

Total protein (g/dL), albumin (g/dL), total bilirubin (mg/dL), AST (U/L), ALT (U/L), ALP (U/L), γ-GTP (U/L), LDH (U/L), total cholesterol (mg/dL), triglyceride (mg/dL), uric acid (mg/dL), BUN (mg/dL), creatinine (mg/dL), CK (U/L), Na (mmol/L), K (mmol/L), Cl (mmol/L), Ca (mmol/L), CRP (mg/dL)

Urinary protein, urine sugar, urineous blood, urobilinogen (qualitative test)

Presence or absence of abnormal findings in waveform

AUC (Area under the plasma concentration versus time curve, Bq·min/mL)

AUC / D (Area under the plasma concentration versus time curve divided by injected dose, min/mL)

Cmax / D (Peak plasma concentration divided by injected dose, /mL)

Tmax (Time to maximum plasma concentration, min)

T1 / 2 (Time from Tmax to half of maximum plasma concentration, min)

Vss (Volume of distribution in steady state, L/kg)

Urine volume (mL) and radioactivity (Bq): Radioactivity and volume will be combined to report radioactivity concentration (Bq/mL).

Stool weight (g) and radioactivity (Bq): Radioactivity and weight will be combined to report radioactivity concentration (Bq/g).

Exhaled volume (mL) and radioactivity (Bq): Radioactivity and volume will be combined to report radioactivity concentration (Bq/mL).

Changes in radioactivity concentration (Bq/mL) in major organs over time: Whole-body imaging (planar and SPECT/CT) is performed to evaluate the distribution in the body at 1 hour, 3 hours, 24 hours after the administration.

Evaluation of treatment effect on CT images by referring to the Revised RECIST guideline (version 1.1): CR (Complete response), PR (Partial response), SD (Stable disease), or PD (Progressive disease)

Evaluation of uptake change in diagnostic \[131I\] NaI scans: CR , PR, SD, or PD

Evaluation of changes in tumor markers: blood thyroglobulin (ng/mL)

Osaka University

Assistant Professor

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Liver Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urogenital Neoplasms

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Immunoconjugates

Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered with or without pre-dosing with vofatamab.

Depending on assigned cohort, \[In111\]-FPI-1967/\[225Ac\]-FPI-1966 will be administered either with or without pre-administration of vofatamab, depending on the RP2D/regimen as determined in the phase 1 portion of the study.

\[225Ac\]-FPI-1966 is a targeted alpha therapeutic that consists of vofatamab, a bifunctional chelate, and actinium-225, an alpha particle emitting radionuclide. In Phase 1, the dose depends on cohort assignment. In Phase 2, the RP2D regimen will be administered.

[225Ac]-FPI-1966

\[111In\]-FPI-1967 is an imaging agent that consists of vofatamab, a bifunctional chelate and indium-111 radionuclide. Participants will receive \[111In\]-FPI-1967 Injection of 185 MBq for imaging.

[111In]-FPI-1967

Vofatamab is a Fibroblast Growth Factor Receptor 3 (FGFR3)-targeting human monoclonal antibody without a radioisotope. In Phase 1, the dose depends on cohort assignment. In Phase 2, if pre-dosing with vofatamab is indicated, the RP2D regimen will be administered.

vofatamab

Julia Kazakin, MD

This first-in-human study evaluates safety, tolerability and distribution of \[225Ac\] FPI-1966, \[111In\]-FPI-1967, and vofatamab in patients with FGFR3-expressing solid tumors.

In phase 1, cohort 1, the potential impact of pre-dose administration of vofatamab on the dosimetry, PK, safety, and tolerability of \[225Ac\]-FPI-1966 and \[111In\]-FPI-1967 will be evaluated.

In later phase 1 cohorts, \[225Ac\]-FPI-1966 will be evaluated at ascending dose levels. Participants will receive \[111In\]-FPI-1967 during the imaging screening period to assess FGFR3 expression and to determine biodistribution and estimate radiation exposure to critical organs.

Once the recommended phase 2 dose (RP2D) or regimen is established and confirmed, three tumour-agnostic expansion cohorts may be initiated in parallel.

A Study of [225Ac]-FPI-1966 in Participants With Advanced Solid Tumours

A Phase 1/2 Study of [225Ac]-FPI-1966, [111In]-FPI-1967, and Vofatamab in Participants With FGFR3-expressing Advanced, Inoperable, Metastatic and/or Recurrent Solid Tumours

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of [225Ac]-FPI-2059 in Adult Participants With Solid Tumours	NCT05605522	Pancreatic Duct... Squamous Cell C... Colorectal Canc... Gastric Cancer Ewing Sarcoma NTSR1 Expressin... Neuroendocrine ...	[225]-FPI-2059 [111In]-FPI-205...	18 Years -	Fusion Pharmaceuticals Inc.
A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients With Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors	NCT06411301	Multiple Myelom... Multiple Myelom... Multiple Myelom...	225Ac-DOTATATE	18 Years -	Jules Bordet Institute
A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours	NCT06147037	Advanced Solid ... Metastatic Colo... Head and Neck S... Non-small Cell ... Pancreatic Duct...	FPI-2053 [111In]-FPI-210... [225Ac]-FPI-206...	18 Years -	Fusion Pharmaceuticals Inc.
Targeted Alpha Therapy Using Astatine (At-211) Against Differentiated Thyroid Cancer	NCT05275946	Thyroid Cancer	Targeted alpha ...	- 18 Years	Osaka University
A Study of [225Ac]-FPI-1966 in Participants With Advanced Solid Tumours	NCT05363605	Advanced Solid ... Head and Neck S... Bladder Carcino... Susceptible FGF... FGFR3 FGFR3 Overexpre... FGFR3 Receptor FGFR3 Protein O... Ovarian Cancer Colorectal Canc... Breast Cancer Liver Cancer Lung Cancer Gastric Cancer	[225Ac]-FPI-196... [111In]-FPI-196... vofatamab	18 Years -	Fusion Pharmaceuticals Inc.
A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients With Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors	NCT06411301	Multiple Myelom... Multiple Myelom... Multiple Myelom...	225Ac-DOTATATE	18 Years -	Jules Bordet Institute

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