TGW211 click-cleavable imaging for HER2-positive cancers

TGW211 for Click-Cleavable Imaging in HER2-Positive Cancers, a Phase 0/I Study.

This trial tries TGW211, a trastuzumab-based agent with a click-cleavable tag, to see if it gives clearer SPECT scans for adults with HER2-positive cancers.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 19 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Radboud University Medical Center (Academic / other)
• Drugs / interventions: trastuzumab, chemotherapy, radiation
• Locations: 1 site (Nijmegen, Gelderland)
• Trial ID: NCT07009184 on ClinicalTrials.gov

What this trial studies

TGW211 combines trastuzumab labeled with Indium-111 via a DOTA-TCO linker and a small-molecule tetrazine trigger to enable click-cleavable release of the radiolabel and faster clearance from normal tissues. In this early Phase 1 interventional study, adults with histologically confirmed HER2-positive solid tumors and at least one measurable lesion receive [111In]In-DOTA-TCO-trastuzumab followed by the tetrazine trigger and undergo SPECT/CT imaging to evaluate tumor-to-background ratios and pharmacokinetics. Eligible participants have ECOG 0–1 and adequate organ and marrow function so that safety and imaging performance can be monitored. Imaging time points and blood sampling are used to determine how rapidly radioactivity clears after trigger administration and to inform optimal timing for future diagnostic or therapeutic use.

Who should consider this trial

Good fit: Adults aged 18 or older with histologically confirmed HER2-positive solid tumors (IHC 3+ or IHC 2+ with FISH+), at least one measurable lesion, ECOG 0–1, and adequate organ and marrow function are ideal candidates.

Not a fit: Patients without HER2 overexpression, those with poor organ function or ECOG >1, pregnant individuals, people unable to travel to the study site, or patients looking for therapeutic rather than imaging benefit are unlikely to receive benefit.

Why it matters

Potential benefit: If successful, this approach could produce clearer images with lower background radiation and enable safer, better-timed use of antibody-based radionuclide techniques.

How similar studies have performed: Antibody-based imaging and pretargeting methods have shown promise in prior preclinical and clinical work, but the specific click-cleavable trastuzumab approach used with TGW211 is largely novel in humans.

Eligibility criteria

Inclusion Criteria:

1. Signed, written informed consent and willing and able to comply with study requirements.
2. Male or Female aged ≥ 18 years.
3. 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.
4. WHO performance status (ECOG) of 0 or 1.
5. Adequate organ and bone marrow function, evidenced by the following laboratory results:

   1. Absolute neutrophil count ≥ 1.5 x 10\^9 /l;
   2. Platelet count ≥ 100 x 10\^9 /l;
   3. Hemoglobin ≥ 9.0 g/dl or 5.6 mmol/l;
   4. Total bilirubin ≤ 1.5 x the upper limit of normal (ULN);
   5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (or ≤ 5.0 x ULN in the presence of liver metastases);
   6. Serum creatinine ≤ 1.5 x ULN; - Estimated Glomerular Filtration Rate (eGFR)\* ≥ 60 ml/min/1.73 m2 ; \*preferably calculated with CKD-EPI formula.

Exclusion Criteria:

1. Medical history of myocardial infarction within 6 months before participation or symptomatic CHF (New York Heart Association Class III to IV).
2. QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec on screening ECG or congenital long QT syndrome.
3. Has a history of (non-infectious) ILD/pneumonitis that required steroids or has current or suspected ILD/pneumonitis.
4. 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.).
5. Has an uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals.
6. Participation in another clinical study with an investigational product during the past 6 weeks.
7. Concurrent enrolment in another clinical study unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.
8. Pregnant or breastfeeding women, where pregnancy is defined as the time between conception and termination of gestation, confirmed by a positive urinary or serum pregnancy test.
9. Women of childbearing potential (WOCBP), defined as women physiologically capable of becoming pregnant and no evidence of post-menopausal status, unless they use highly effective methods of contraception or abstain from sexual activity for 30 days after investigational drug administration. Male partners of female patients should also use a condom during intercourse for 30 days after investigational drug administration to the partner to prevent them from fathering a child.
10. Male patients in the reproductive age, not willing or able to use a condom or abstain from sexual activity for 30 days after investigational drug administration. WOCBP partners of sexually active male patients should also use a highly effective contraception method during intercourse for 30 days after investigational drug administration of the partner.
11. Known allergy or hypersensitivity to any of the investigational drugs or its excipients.
12. Any condition which, in the opinion of the investigator, would preclude participation in the study.
13. Second active malignancy.

Where this trial is running

Nijmegen, Gelderland

• Radboud University Medical Center — Nijmegen, Gelderland, Netherlands (Recruiting)

Conditions HER2 Positive Solid Tumor