Novartis announced the results of a pivotal phase II trial demonstrating that patients with locally advanced (laBCC) or metastatic basal cell carcinoma (mBCC) taking the investigational oral compound LDE225 (sonidegib) had marked and sustained tumour shrinkage after a median follow-up of 13.9 months. The data were revealed for the first time today in an oral presentation at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago

"These results represent an important milestone in the clinical development of LDE225, as well as in our research strategy to develop new therapies for patients with unmet needs," said Alessandro Riva, managing director, Global Head, Novartis Oncology Development and Medical Affairs. "These data will form the basis for the filing of another important new medicine for a skin-related disease in which Novartis is building a leading position."

The trial assessed the efficacy and safety of two oral doses of LDE225, 200 mg and 800 mg, in patients with laBCC or mBCC. The primary endpoint was the objective response rate (ORR), defined as the proportion of patients with complete or partial tumor response, or shrinkage, as measured by a central review committee. The study met the primary endpoint in both treatment arms with ORRs of 41.8 per cent (95 per cent) confidence interval in the 200 mg arm and 32.5 per cent (95 per cent CI: 25.1, 40.5) in the 800 mg arm. More specifically, 47.0 per cent of patients with laBCC and 15.4 per cent of patients with mBCC, in the 200 mg arm, and 35.2 per cent of patients with laBCC and 17.4 per cent of patients with mBCC in the 800 mg arm, achieved an objective response.

Secondary endpoints included duration of response (DoR), progression-free survival (PFS) and time to tumor response (TTR), a measure of how quickly the tumor responded to treatment. Median DoR for patients with laBCC in both treatment arms could not be estimated since the majority of patients who had a response had no event at the time of the analysis (an event is defined as progression or death due to any cause) Median DoR was 8.3 months for patients with mBCC treated with LDE225 800 mg; however, it could not be estimated for patients with mBCC in the 200 mg arm because they had no event at the time of the analysis. The median PFS for patients with laBCC in both treatment arms could not be estimated since the majority of patients had no event at the time of the analysis. The median PFS per central review for patients with mBCC was 13.1 months in the 200 mg arm and 7.6 months in the 800 mg arm. Median TTR per central review for patients with laBCC was 3.9 months (95 per cent) in the 200 mg arm and 3.7 months (95 per cent) in the 800 mg arm, and 4.6 months (95 per cent) and 1.0 month (95 per cent) for patients with mBCC in the 200 mg and 800 mg arms, respectively.

The most common Grade 3/4 adverse events (AEs) reported in >=2 per cent of patients receiving treatment with the 200 mg dose were elevated levels of creatine phosphokinase (6.3 per cent), increased lipase (5.1 per cent), hypertension (2.5 per cent), asthenia, or weakness (2.5 per cent) and muscle spasms (2.5 per cent). The most common Grade 3/4 AEs, reported in >=2 per cent of patients receiving treatment with the 800 mg dose were elevated levels of creatine phosphokinase (12.7per cent), increased lipase (5.3 per cent), muscle spasms (5.3 per cent), decreased weight (5.3 per cent), decreased appetite (4.0 per cent), rhabdomyolysis, or the breakdown of muscle fibers (3.3per cent), nausea (2.7 per cent), hypertension (2.7per cent), increased alanine aminotransferase (2.7per cent), increased aspartate aminotransferase (2.7 per cent), fatigue (2.0 per cent), syncope, or fainting (2 per cent), anaemia (2 per cent), dehydration (2 per cent), hyperkalemia (2 per cent) and myalgia, or muscle pain (2.0per cent)  Overall, Grade 3/4 events were observed less frequently in the 200 mg group (30.4 per cent) than in the 800 mg group (56.0 per cent).

Basal cell carcinoma (BCC) accounts for more than 80 per cent of non-melanoma skin cancers. Worldwide incidence of BCC is rising by 10 per cent each year due to factors such as an aging population and increased ultraviolet exposure. Although BCC rarely becomes advanced or metastatic, there are few treatment options at these stages of the disease.

"LDE225 showed marked tumor responses in patients with locally advanced or metastatic basal cell carcinoma," said lead investigator, Michael Robert Migden, managing director, University of Texas managing director, Anderson Cancer Center. "If approved, LDE225 could provide an important treatment option for patients suffering from this disease that can be disfiguring and life-threatening in advanced stages."

The data from this pivotal trial will serve as the basis for worldwide regulatory filings for the 200 mg dose of LDE225 in advanced basal cell carcinoma.