Cascadian Therapeutics Inc (USA) (NASDAQ:CASC) announced that following a recent meeting with the U.S. Food and Drug Administration (FDA) and discussions with the Company’s external Steering Committee, it has amended the HER2CLIMB Phase 2 clinical trial of tucatinib (also known as ONT-380) by increasing the sample size so that, if successful, the trial could serve as a single pivotal study to support registration.
This decision is supported by the most recent data from the Company’s ongoing Phase 1b study evaluating the same “triplet combination” therapy being investigated in the amended Phase 2 trial, which is tucatinib in combination with capecitabine and trastuzumab for patients with metastatic or locally advanced HER2-positive breast cancer, including patients with and without brain metastases. Tucatinib is an oral, small molecule kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR.
HER2CLIMB is an ongoing randomized, controlled pivotal trial evaluating tucatinib in combination with trastuzumab (Herceptin®) and capecitabine (Xeloda®) in heavily pre-treated patients with advanced HER2-positive breast cancer with or without brain metastases.
“We are extremely pleased with the outcome of our recent interactions with the FDA, and we have decided to amend the current Phase 2 clinical trial of tucatinib so that, if successful, HER2CLIMB could serve as a single pivotal registration trial and potentially provide us with a more efficient path to market,” commented Scott Myers, President and CEO of Cascadian Therapeutics.
“We look forward to continuing a collaborative relationship with the agency and our clinical investigators as we advance the development of tucatinib in combination in the third-line metastatic breast cancer setting where there is no single standard-of-care and a need for more tolerable therapeutic options. The improvement in the updated data from our Phase 1b “triplet combination” study reinforces our strategy with tucatinib in this patient population.”
Updated Phase 1b trial results for the triplet combination show that the combination (tucatinib with capecitabine and trastuzumab) continues to be well tolerated, with the updated median progression-free survival (PFS) increasing to 7.8 months, an overall response rate (ORR) of 61 percent and a median duration of response (MDR) of 10 months. Patients in the Phase 1b triplet combination previously received a median of 3 HER2-targeted agents, such as trastuzumab, pertuzumab, lapatinib or T-DM1. Poster presentations on the amended HER2CLIMB pivotal trial and the updated Phase 1b “triplet combination” trial data will be presented at the 2016 San Antonio Breast Cancer Symposium (SABCS), December 6-10, 2016.
“The more mature dataset from the Phase 1b trial continues to show tucatinib may be combined with other current targeted therapies to achieve durable responses in patients who have received multiple prior lines of therapy,” said Erika Hamilton, M.D., Director of Breast and Gynecology Cancer Research at Sarah Cannon Research Institute. “Tucatinib in combination appears to be well-tolerated, potentially making it a highly desirable HER2 therapy for a patient population that vitally needs new options. An active agent showing systemic activity, with a tolerable safety profile and early signs of activity in HER2-positive brain metastases, would represent a meaningful advancement in treating metastatic breast cancer.”
HER2CLIMB Pivotal Trial
HER2CLIMB is a randomized (2:1), double-blind, controlled pivotal clinical trial comparing tucatinib vs. placebo in combination with capecitabine and trastuzumab in patients with locally advanced or metastatic HER2-positive breast cancer who have had prior treatment with a taxane, trastuzumab, pertuzumab and T-DM1. Following a meeting with the FDA, the primary endpoint remains PFS based upon independent radiologic review, and the sample size will increase to approximately 480 patients, including patients already enrolled in the trial. Key objectives related to assessing activity in brain metastases include a key secondary endpoint of PFS in a subset of patients with brain metastases. All patients will be followed for overall survival. HER2CLIMB is currently enrolling in the United States and Canada and is expected to expand into Europe, Australia and Israel. Details of the amended HER2CLIMB clinical trial design will be presented in a poster session (OT1-02-09) at SABCS on Wednesday, December 7, 2016 beginning at 5:00 p.m. CST.
Updated Phase 1b Triplet Study Findings at SABCS
Results reported in June 2016 showed a median PFS of 6.3 months and ORR of 58 percent. Updated data from the SABCS poster (P4-21-01) of the Phase 1b study show encouraging safety and anti-tumor activity in patients with and without brain metastases, with an updated median PFS of 7.8 months (a 24 percent improvement over prior median PFS), ORR of 61 percent and a median duration of response of 10 months. Patients with and without brain metastases had similar response rate. The combination of tucatinib with trastuzumab and capecitabine was well-tolerated. Most treatment-emergent adverse events were Grade 1, with few tucatinib dose reductions and no required prophylactic use of antidiarrheal agents. Updated results will be presented in a poster session at SABCS on Friday, December 9, 2016 beginning at 7:30 a.m. CST. (Original Source)
Shares of Cascadian are rising 1.79% to $6.25, or up $0.11 in pre-market trading Wednesday. CASC has a 1-year high of $10.98 and a 1-year low of $4.90. The stock’s 50-day moving average is $1.27 and its 200-day moving average is $1.18.
On the ratings front, Cascadian has been the subject of a number of recent research reports. In a report issued on November 7, Jefferies Co. analyst Gena Wang reiterated a Buy rating on CASC, with a price target of $3, which implies a downside of 51% from current levels. Separately, on October 10, Cowen’s Boris Peaker reiterated a Buy rating on the stock .
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Gena Wang and Boris Peaker have a yearly average loss of 5.2% and a return of 12.4% respectively. Wang has a success rate of 38% and is ranked #3884 out of 4262 analysts, while Peaker has a success rate of 42% and is ranked #263.
Cascadian Therapeutics, Inc. is a clinical-stage biopharmaceutical company, engages in the development of therapeutic products for the treatment of cancer. Its lead product candidate ONT-380, is an orally active and selective small-molecule HER2 inhibitor. It also develops preclinical product candidates in oncology using Chk1 kinase inhibitor and protocell technology.