Clinical Study to Evaluate Safety and Dosing of CA9hu-1 in Patients With Advanced Solid Tumours
Status:
Not yet recruiting
Trial end date:
2026-01-01
Target enrollment:
Participant gender:
Summary
Carbonic anhydrase IX (CA IX) has been implicated in the progression of most solid tumours
and expression has been demonstrated in clinical samples from a variety of solid cancers.
High expression is often associated with high grade or metastatic disease and poor prognosis.
CA IX is not expressed in normal tissue, potentially providing a cancer-associated target
that would not likely result in significant interruption of normal biologic function in
organs not affected by cancer. A humanized monoclonal antibody CA9hu-1 has shown robust
activity in a variety of tumour models including models of ovarian, prostate, breast,
pancreatic, colon and lung where tumour growth and metastasis are inhibited when CA9hu-1 is
used as a monotherapy. Enhancement of chemotherapy has also been demonstrated in several
models in combination with CA9hu-1. CA IX is also expressed by tumour-associated cells
(angiogenic endothelium, tumour-associated macrophages), which also drive cancer progression.
Thus, targeting CA IX with CA9hu-1 in cancer patients is expected to affect multiple pathways
and multiple tumour compartments that are important to tumour progression. Taken together,
there is strong rationale for developing hu-CA91 for the treatment of advanced cancer. The
present study was designed to establish safety and toxicity profile and maximum tolerated
dose of CA9hu-1, evaluate pharmacokinetics, investigate the presence of anti-drug antibody,
to document anti-tumour activity at a clinically relevant dose, and to document the use of
[18F]FLT-PET as a biomarker for detection of early tumour response at a clinically relevant
dose.