TGW211 for Click-Cleavable Imaging in HER2-Positive Cancers.
ConditionHER2 Positive Solid Tumor
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorRadboud University Medical Center
About this trial
In recent years, there is increasing interest in antibodies for imaging, antibody-drug conjugates (ADC) and targeted radionuclide therapy (TRT). With these techniques, antibodies are used as a vector to deliver a cytotoxic drug or radionuclide for therapy or nuclear medicine imaging. One such antibody-based vector suitable for delivering a cytotoxic drug or radionuclide is trastuzumab, which targets HER2 that is overexpressed in cancers such as breast, gastric and gastroesophageal junction carcinomas. Unfortunately, antibodies generally have a very long circulation time (\>20-30 days) that often result in unfavorable background noise in the healthy organs in imaging or toxicity when trastuzumab is bound to a therapeutic radionuclide for radioimmunotherapy. There is thus a need to increase the speed of excretion of antibodies or release the antibody from its payload. Ideally, the clinician would like to appropriately time the elimination of radioactivity to achieve an optimal tumor to non-tumor ratio. To this aim, Tagworks Pharmaceuticals developed a new class of chemically cleavable radiolabeled conjugates that release the radiolabel on demand upon reaction with a small molecule "the trigger" (TRG001).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Signed, written informed consent and willing and able to comply with study requirements.
Male or Female aged ≥ 18 years.
Histologically confirmed HER2-positive cancer (IHC 3+ or IHC 2+ AND FISH+) with at least 1 measurable target lesion of at least 10 mm on CT or MRI based on RECIST v1.1, assessed by the investigator to enable adequate SPECT/CT imaging.
WHO performance status (ECOG) of 0 or 1.
Disqualifiers
Medical history of myocardial infarction within 6 months before participation or symptomatic CHF (New York Heart Association Class III to IV).
QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec on screening ECG or congenital long QT syndrome.
Has a history of (non-infectious) ILD/pneumonitis that required steroids or has current or suspected ILD/pneumonitis.
Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g, pulmonary embolism within 3 months of trial participation, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.).
Trial design
Design model
Sequential
Treatments tested in this trial
[111In]In-DOTA-TCO-trastuzumab
Drug\[111In\]In-DOTA-TCO-trastuzumab is a chemically cleavable \[111In\]In-labeled trastuzumab conjugate that is administered first to the patient, it accumulates in HER2-positive tumors and internalizes in HER2-expressing tumor cells.
Small molecule tetrazine trigger component
DrugTRG001 is a small molecule tetrazine trigger that reacts with \[111In\]In-TGW211-DC in blood and extracellular space thus releasing a fast clearing \[111In\]In-DOTA containing fragment which is rapidly eliminated via the kidney. Because of its non-cell permeable nature, TRG001 does not reach \[111In\]In-TGW211-DC inside tumor cells and therefore the radioactivity inside tumor cells is retained by the tumor.
Treatment groups
19 Participants
are divided into 1 treatment groupGroup A: Click-chemistry using [111In]In-DOTA-TCO-trastuzumab and trigger component TRG001 (TGW211)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Frequency and severity of Adverse Events using the CTCAE version 5.0.
Time frame
From enrollment to end of treatment at 14 days after last dose of investigational product.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Radboud University Medical Center
Lead sponsor
Tagworks Pharmaceuticals BV
Collaborator
Source ClinicalTrials.gov