On January 5, 2017 Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported an overview of recent progress for its investigational drug portfolio in addition to several anticipated key objectives for 2017 (Press release, Cascadian Therapeutics, JAN 5, 2017, View Source [SID1234517272]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"In 2016, we refocused our resources on the development of our small molecule HER2 inhibitor, tucatinib, and have entered 2017 with clear priorities and with an enhanced team that has late-stage development experience," said Scott D. Myers, President and Chief Executive Officer of Cascadian Therapeutics. "In the fourth quarter of 2016, following a very collaborative meeting with the FDA, we amended the ongoing HER2CLIMB Phase 2 trial of tucatinib so that, if successful, HER2CLIMB could serve as a single pivotal registration trial. Updated data from the ongoing Phase 1b Triplet combination study continues to show a tolerable safety profile and encouraging anti-tumor activity in a heavily pre-treated population, including those with and without brain metastases. With a clear, accelerated regulatory pathway for the advancement of tucatinib in the United States, a solid balance sheet and an expanded talented leadership team, we plan to spend more time on our ex-U.S. strategy for tucatinib and to continue building for success in 2017 and beyond."
Recent Progress Update
Tucatinib — targeted HER2 inhibitor
In December 2016, Cascadian announced that following a recent meeting with the U.S. Food and Drug Administration (FDA) it has amended the HER2CLIMB Phase 2 clinical trial of its investigational product, tucatinib, by increasing the sample size so that, if successful, the trial could serve as a single pivotal study to support registration. HER2CLIMB is a randomized (2:1), double-blind, controlled pivotal clinical trial comparing tucatinib in combination with capecitabine and trastuzumab 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. The primary endpoint is progression-free survival (PFS) based upon independent radiologic review, and the sample size is increased to approximately 480 patients, including patients who enrolled in HER2CLIMB to date. Patients will also be followed for overall survival, which is a secondary endpoint. Key objectives related to assessing activity in brain metastases include a secondary endpoint of PFS in a subset of patients with brain metastases.
In December 2016, researchers presented updated results from the Company’s ongoing Phase 1b Triplet combination study (tucatinib with capecitabine and trastuzumab) at the 2016 San Antonio Breast Cancer Symposium (SABCS). Results showed that tucatinib continues to be well tolerated in this combination, with an updated median progression-free survival (PFS) of 7.8 months, an overall response rate (ORR) of 61 percent and a median duration of response (DoR) of 10 months. Patients treated with the Triplet combination previously received a median of 3 HER2-targeted agents, such as trastuzumab, pertuzumab, lapatinib and T-DM1.
CASC-578 – a novel Chk1 cell cycle inhibitor
During the fourth quarter and during 2016, the following progress was made in the CASC-578 program:
Non-GLP repeat dose tolerability studies were conducted in rats and cynomolgus monkeys to establish drug tolerability and identify dose ranges to test in future IND enabling GLP toxicology studies.
A GLP safety pharmacology study was conducted in cynomolgus monkeys to evaluate multiple cardiovascular safety endpoints. The results of this study indicate CASC-578 has an acceptable safety profile at the doses tested and support further development of the drug.
CASC-578 was evaluated in vitro in a large panel of tumor derived cell lines to define its activity as a single agent in both solid and hematological cancers and to identify potential biomarkers to define tumor genotypes most likely to respond to the drug. The results of this study demonstrated CASC-578 can inhibit the growth of a subset of tumor derived cell lines from both solid and hematological malignancies with IC50 values as low as 30 nM and several candidate biomarkers were identified that correlate with potency in responsive cell lines.
To better define the pharmacological activity and therapeutic index of CASC-578, several in vivo studies were conducted in mice using human xenograft models of acute leukemia, mantle cell lymphoma and non-small cell lung cancer. The results of these experiments showed CASC-578 inhibited, and in some cases, regressed established tumors as a single agent.
Corporate Update
In January 2017, the Company announced the appointment of Marc L. Lesnick, Ph.D., as Senior Vice President, Regulatory Affairs and Quality.
As of September 30, 2016, cash, cash equivalents and investments totaled $71.6 million and no debt. The Company plans to provide 2017 guidance in its fourth quarter and year-end 2016 results announcement.
2017 Key Objectives Planned
Focus on HER2CLIMB pivotal trial enrollment: Expand the HER2CLIMB trial to sites in Europe, Australia and Israel in the first half of 2017.
Report new data at scientific meetings: Report new data analyses from tucatinib and the Chk1 cell cycle inhibitor at scientific meetings in 2017.
Explore tucatinib’s utility in other clinical settings: Support the initiation of select investigator-sponsored combination trials, including trials in HER2-positive amplified, metastatic colorectal cancer and in combination with palbociclib and letrozole in HER2-positive, hormone-receptor positive metastatic breast cancer.
Define next steps for CASC-578: Complete pharmacology studies in the first half of 2017 and make go/no-go decision on IND-enabling studies for CASC-578 in the second half of 2017.
Pursue capital options: Evaluate all available financing vehicles, including non-dilutive options such as out-licensing tucatinib regional rights.