Novartis Phase II study LDE225 for advanced basal cell carcinoma meets primary endpoint -
Novartis announced today the results of a pivotal Phase II tests demonstrating that patients with locally advanced (laBCC) or metastatic basal cell carcinoma (mBCC) taking the experimental oral compound LDE225 (sonidegib) had marked and sustained removal of the tumor 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 (abstract # 009a).
"These results represent an important step in the clinical development of LDE225 and in our research strategy to develop new therapies for patients with unmet needs," said Alessandro Riva, MD, Global Head, Novartis oncology development and medical Affairs. "These data provide the basis for the filing of an important new drug for a disease of the skin in which Novartis built a leading position."
the test evaluated the efficacy and safety of two oral doses of LDE225, 0 mg and 800 mg in patients with laBCC and mBCC. the primary endpoint was objective response rate (ORR), defined as the proportion of patients a complete or partial tumor response, or withdrawal, as measured by a central review committee. the study met the primary endpoint in both treatment arms with Orrs 41.8% (95% confidence interval [CI]: 30.8, 53.4) in the 0 mg arm and 32.5% (95% CI: 25.1, 40.5) in the 800 mg arm. Specifically, 47.0% of patients and 15.4% laBCC patients mBCC, in the arm 0 mg, and 35.2% of patients laBCC and 17.4% of patients in the arm mBCC 800 mg , achieved an objective response.
secondary endpoints included duration of response (DOR), progression-free survival (PFS) and tumor response (TTR), a measure of how quickly the tumor responded to treatment. Median DoR for patients with laBCC in both treatment arms can not be estimated because the majority of patients who have had a response had no case at the time of the analysis (an event is defined as progression or death due to a cause). Median DoR was 8.3 months for patients treated with mBCC LDE225 800 mg; however, it could not be estimated for patients mBCC in the arm 0 mg because they had no case at the time of analysis. The median PFS for patients with laBCC in both treatment arms can not be estimated since the majority of patients had no case at the time of analysis. The median PFS by central examination for patients with mBCC was 13.1 months in the 0 mg arm and 7.6 months in the 800 mg arm. Median TTR by central examination for patients with laBCC was 3.9 months (95% CI: 3.6, 4.2) in the 0 mg arm and 3.7 months (95% CI: 2.6, 3.8) in the arm 800 mg, and 4.6 months (95% CI: 1.8, 7.4) and 1.0 months (95% CI: 1.0, 2.1) for patients in mBCC 0 mg and 800 mg, respectively arm
grade 3/4 the most frequent adverse events (AEs.) reported in ≥2% of patients receiving the 0 mg dose were high levels creatine phosphokinase (6.3%), lipase increased (5.1%), hypertension (2.5%), asthenia or weakness (2.5%) and muscle spasms (2.5%) . The most common grade 3/4 AEs reported in ≥2% of patients receiving the 800 mg dose were high levels of creatine phosphokinase (12.7%), lipase increased (5.3%) , muscle spasms (5.3%), decreased weight (5.3%), decreased appetite (4.0%), rhabdomyolysis, or the breakdown of muscle fibers (3.3%), nausea (2.7%), hypertension (2.7%), increased alanine aminotransferase (2.7%), increased aspartate aminotransferase (2.7%), fatigue (2, 0%), syncope, or fainting (2%), anemia (2%), dehydration (2%), hyperkalemia (2%) and myalgia or muscle pain (2.0%). Overall grade 3/4 events were observed less frequently in the 0 mg group (30.4%) than in the 800 mg group (56.0%).
Basal cell carcinoma (BCC) represents over 80% of non-melanoma skin cancers. the global incidence of BCC increased by 10% each year due to factors such as the aging population and the increased exposure to ultraviolet light. Although BCC rarely becomes advanced or metastatic there are few treatment options for 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, MD, University of Texas MD Anderson Cancer Center. "If approved, LDE225 could provide an important treatment option for patients suffering from this disease can be disfiguring and life-threatening in the advanced stages."
The data from this pivotal trial basis for worldwide regulatory filings for the 0 mg dose of LDE225 in advanced basal cell carcinoma.
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