Puma Biotechnology declares results of Phase II ‘basket’ Clinical Trial

Phase II ‘basket’ clinical trial of PB272 (neratinib) in patients with tumors harboring HER2 or HER3 mutations results were declared by Puma Biotechnology as published in the journal Nature.

The Phase II SUMMIT trial is a global, multi-histology, open-label, precision-medicine ‘basket’ study evaluating the safety and efficacy of neratinib administered daily to patients with a wide variety of solid tumors with activating HER2 or HER3 mutations. In a bid to evaluate the contributions of both genetic mutation and cancer type on  individual patients’ response to neratinib.

Alan H. Auerbach, Puma’s Chief Executive Officer and President said “The basket trial design utilized for SUMMIT is enabling researchers to evaluate the clinical potential of neratinib in multiple cancer types, rather than limiting exploration to one tumor type at a time. SUMMIT is also significant in that it will provide the largest body of clinical data to date on the use of an irreversible pan-HER inhibitor in patients who have solid tumors with somatic HER2 or HER3 mutations.”

Data encompassses enrollment of 141 patients n the neratinib monotherapy arm of the trial, including 124 patients with HER2 mutations and 17 patients with HER3 mutations. This included patients with 21 unique tumor types, with the most common being breast, lung, bladder and colorectal cancer. Researchers observed 30 distinct HER2 and 12 distinct HER3 mutations among these patients, with the most frequent HER2 variants involving amino acids S310, L755, A755_G776insYVMA and V777.

The neratinib safety profile observed in the SUMMIT study is consistent with that observed previously in metastatic patients with HER2 amplified tumors. The study showed that the most frequently observed adverse reaction was diarrhea. All patients in the SUMMIT study received prophylactic loperamide (16 mg per day initially) for the first cycle of treatment in order to reduce neratinib-related diarrhea, and with this anti-diarrheal prophylaxis and management, diarrhea was not a treatment-limiting side effect in SUMMIT.

Image Source : Puma Biotechnology