Puma Biotechnology provided an update on the development program for its HER2-targeted drug neratinib (Nerlynx)

In Clinical Studies News by Barbara Jacoby

By: Staff Reporter

From: precisiononcologynews.com

On the third day of the 38th annual JP Morgan Healthcare Conference, Puma Biotechnology provided an update on the development program for its HER2-targeted drug neratinib (Nerlynx).

Alan Auerbach, CEO of Puma Biotechnology, discussed the development of neratinib (Nerlynx), which the company has been exploring in the Phase II SUMMIT basket trial across multiple tumor types with HER2, HER3, or EGFR mutations or with EGFR gene amplification. The drug has already been approved by the US Food and Drug Administration and has marketing authorization from the European Commission for the extended adjuvant treatment of early stage, HER2-positive breast cancer after adjuvant trastuzumab-based therapy. Auerbach said that the drug was recently commercialized in Germany, the UK, and Australia, and that neratinib will become available across Europe in the next two years.

He also addressed the high discontinuation rates with neratinib due to diarrhea. In the Phase III study that led to the drug’s approval, nearly 40 percent of patients had grade 3 or more severe diarrhea, and around 17 percent discontinued the trial due to this adverse event. However,prophylactic use of anti-diarrheal medications was not mandatory in this study, and Puma started the CONTROL trial to see if the use of anti-diarrheal drugs could lessen the side effects. Based on data so far, loperamide prophylaxis appeared to reduce the incidence and severity of diarrhea. The company has also rolled out an education program about starting patients on a lower dose and escalating that to increase tolerability of the drug. In Q4, almost 29 percent of patients started the drug on a reduced dose, Auerbach said.

Despite this side effect, neratinib has an advantage over other HER2-targeted agents, Auerbach noted, since it can cross the blood brain barrier. This benefit became apparent in the Phase III NALA trial, which compared neratinib and the chemotherapy capecitabine (Genentech’s Xeloda) against lapatinib (Novartis’ Tykerb) plus capecitabine in third line HER2-positive metastatic breast cancer. The data presented last year at the American Society of Clinical Oncology’s annual meeting showed that the combination of neratinib and capecitabine reduced the risk of death and the incidence of central nervous metastases compared to lapatinib and capecitabine. The FDA has accepted Puma’s supplemental new drug application based on data submitted from this study, and the company anticipates hearing back from the agency in April.

Additionally, Auerbach talked about progress in the SUMMIT basket trials targeting tumors with mutations in EGFR exon 18, HER2, or HER4. The design of the trial allows that if at least one of the first seven enrolled patients respond to the therapy, the cohort will be expanded to 18 patients. If at least four patients respond during the second stage, then the cohort will be even further expanded or broken out into a separate trial.

Auerbach said that the HER2-mutated breast cancer cohort will be expanded. For the hormone receptor-positive/HER2-negative and HER2-mutated metastatic breast cancer cohort, Puma is planning to seek accelerated approval. The HER2-mutated cervical cancer cohort will also expand, and Auerbach thinks that monotherapy data from this indication can also be used to file for accelerated approval based on overall response rate and duration of response. Puma is hoping to meet with the FDA by year end or in early 2021 to discuss expedited approval for its new drug applications.

Puma is also conducting a trial in which researchers are using the Alman HER-Seq Assay Kit to test metastatic breast and cervical cancer patients for somatic HER2 mutations in their blood. In the trial, patients are eligible for testing at three- to six-month intervals to monitor them for progression. If mutations are detected in ctDNA, patients may be eligible for treatment with neratinib. The company wants to expand screenings in order to expedite enrollment in the SUMMIT trials.