US-based, orphan oncology company Ariad Pharmaceuticals has begun a Phase l/ll clinical trial of AP32788, an investigational tyrosine kinase inhibitor (TKI), to treat non-small cell lung cancer (NSCLC) with specific mutations in epidermal growth factor receptor (EGFR) or HER2.
The molecule has been designed to target the unmet need in patients with NSCLC driven by exon 20 insertion mutations in EGFR and HER2.
Around 2% of NSCLC patients reportedly have HER2 mutations, with the majority having exon 20 insertion mutations.
The Phase l/ll trial will be performed in two parts, including a dose escalation phase and an expansion phase.
The initial Phase l dose-escalation multicentre trial will enrol advanced NSCLC patients, who will be refractory to standard available therapies.
The primary objective of the trial’s Phase l segment is to identify the safety, tolerability, pharmacokinetic profile, and recommended Phase ll dose (RP2D) of orally given AP32788.
The company plans to enrol around 20 to 30 patients in this portion of the trial.
The Phase ll expansion phase of the trial will enrol four histologically and molecularly defined patient cohorts, which include NSCLC patients with EGFR exon 20 activating insertions with no active, measurable central nervous system (CNS) metastases; NSCLC patients with HER2 exon 20 activating insertions or point mutations with no active, measurable CNS metastases.
The remaining two patient cohorts are NSCLC patients with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases; and NSCLC with other targets, against which AP32788 has shown preclinical activity with or without active, measurable CNS metastases.
The trial’s Phase ll segment will enrol around 80 patients and evaluate anti-tumour activity of AP32788 in the molecularly defined patient populations.
Ariad Pharmaceuticals chief scientific officer and research and development president Tim Clackson said: "In the preclinical data presented at the AACR meeting last month, AP32788 demonstrated the ability to inhibit all tested EGFR and HER2 mutants, including exon 20 insertion mutants.
"We are pleased to be advancing AP32788, the next promising cancer medicine in the ARIAD pipeline, into clinical study for patients who currently have no targeted treatment options in these orphan oncology disease subsets."