Clinical Trials

Date: 2017-04-02

Type of information: Presentation of results at a congress

phase: 1b

Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting

Company: BeiGene (China)

Product: BeiGene-283/BGB-283

Action mechanism: protein inhibitor/BRAF inhibitor. BGB-283 is a BRAF inhibitor. Discovered by BeiGene scientists, BGB-283 has unique RAF dimer and EGFR inhibition activities. BGB-283 has shown antitumor activities in preclinical models and in cancer patients not only in tumors with BRAF V600E mutation but also those with non-V600E BRAF mutations and KRAS/NRAS mutations. BGB-283 was partnered with Merck KGaA in 2013 prior to the initiation of its clinical development. Pursuant to the license agreements for territories in and outside China respectively, BeiGene has exclusive development and commercial rights to BGB-283 in China, and Merck KGaA has an exclusive license to develop and manufacture BGB-283, and, subject to the exercise of a continuation option based on review of Phase I data, to commercialize and manufacture BGB-283 in markets outside of China.

Disease: B-RAF or K-RAS/N-RAS mutated solid tumors, pancreatic cancer

Therapeutic area: Cancer - Oncology

Country: Australia, New Zealand

Trial details: The multicenter, open-label Phase I trial of BGB-283 conducted in Australia and New Zealand is comprised of two parts – Phase IA (dose-escalation) and Phase IB (dose-expansion) in patients with B-RAF or K-RAS/N-RAS mutated solid tumors or patients with pancreatic cancer. The dose-expansion portion of the trial was designed to evaluate the safety and efficacy of BGB-283 at the recommended Phase II dose of 30 mg QD established in the Phase IA part of the trial. The expansion cohorts include patients with B-RAF V600-mutated cancers including melanoma, either naïve or having developed resistance to existing B-RAF or MEK inhibitors, colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and papillary thyroid cancer (PTC), as well as patients with other B-RAF-mutated solid tumors. They also include patients with K-RAS/N-RAS-mutated endometrial cancer, NSCLC, and CRC, as well as patients with other K-RAS/N-RAS-mutated solid tumors and patients with pancreatic cancer.

Latest news:

• • On April 2, 2017, BeiGene presented data from the Phase IB dose expansion study of RAF dimer inhibitor BGB-283 in patients with B-RAF or K-RAS/N-RAS mutated solid tumors in an oral presentation during a Clinical Trials Plenary Session at the 2017 American Association for Cancer Research (AACR) Annual Meeting in Washington. BGB-283 has demonstrated activity in both B-RAF and K-RAS-mutated tumors in preclinical studies and in the Phase IA dose escalation portion of this Phase I study. In the Phase IB portion, BGB-283 has generally been well-tolerated at a dose of 30 mg once a day and has continued to show antitumor activity not only in subjects with B-RAF V600-mutated solid tumors, but also in subjects with K-RAS-mutated solid tumors.
• Summary of Results: The safety analysis, which included 96 patients as of the September 12, 2016 cut-off, suggested that BGB-283 was generally well-tolerated at 30 mg QD, with most drug-related adverse events (AEs) being grades 1 or 2 in severity. The most frequent drug-related AEs (?10%) of any grade were fatigue (38.5%), dysphonia (26.0%), decreased appetite (21.9%), palmar-plantar erythrodysaesthesia syndrome (21.9%), thrombocytopenia (19.8%), dermatitis acneiform (17.7%), diarrhea (16.7%), rash (16.7%), nausea (15.6%), hypertension (11.5%), and glossodynia (10.4%). The most frequent drug-related grade 3-4 AEs (?2%, 2 patients or more) included fatigue (7.3%), hypertension (6.3%), thrombocytopenia (6.3%), pyrexia (3.1%), hyponatremia (2.1%), anemia (2.1%), neutropenia (2.1%), febrile neutropenia (2.1%), decreased platelet count (2.1%), increased alanine aminotransferase (2.1%), increased gamma-glutamyltransferase (2.1%), and sepsis (2.1%).
• The cut-off for the efficacy analysis was September 17, 2016. In seven patients with B-RAF V600-mutated melanoma (including one V600K and one V600R) who were naïve to B-RAF or MEK inhibitors, there were three partial responses (PRs) and three cases of stable disease (SD). In three patients with B-RAF V600-mutated PTC, there was one PR and two cases of SD. In six patients with K-RAS-mutated NSCLC, there was one PR and two cases of SD. In ten patients with solid tumors with B-RAF non-V600 mutations or solid tumors with B-RAF V600 mutations that are not included in other cohorts, there were two PRs, in one patient with BRAF V600E-mutated melanoma and one with BRAF V600E-mutated ovarian cancer, and three cases of SD. In two patients with B-RAF V600-mutated NSCLC, there was one unconfirmed PR and one case of SD.
• Additional cases of SD were observed in four of six melanoma patients with B-RAF V600-mutated melanoma who had responses to but developed resistance against B-RAF or MEK inhibitors, nine of 13 patients with B-RAF V600-mutated CRC, five of five patients with K-RAS-mutated endometrial cancer, 12 of 20 patients with K-RAS/N-RAS-mutated CRC, and 10 of 21 patients with other K-RAS/N-RAS-mutated solid tumors or pancreatic cancer.
• In the Phase IA portion of the study, confirmed objective responses included a complete response in a patient with B-RAF V600E-mutated melanoma, and two PRs, one in a patient with B-RAF V600E-mutated thyroid cancer and one in a patient with K-RAS-mutated endometrial cancer.
• • On March 2, 2017, BeiGene announced that it will present data from the Phase IB dose expansion study of RAF dimer inhibitor BGB-283 in patients with B-RAF or K-RAS/N-RAS mutated solid tumors in an oral presentation during a Clinical Trials Plenary Session at the 2017 American Association for Cancer Research (AACR) Annual Meeting. (A Phase IB study of RAF dimer inhibitor BGB-283 in patients with B-RAF or K-RAS/N-RAS mutated solid tumors. Presenter: Dr. Jayesh Desai and Abstract #2010: Hu N. et al., BTK inhibitor BGB-3111 demonstrates anti-tumor activity in solid tumor models. Mon., Apr. 3, 8:00 AM -12:00 PM
• In addition, the company expects a decision in the first quarter of 2017 from its partner Merck KGaA on its continuation option to develop and commercialize BGB-283 outside China after Merck’s review of Phase I data.

   

Is general: Yes