On June 14, 2016 Cascadian Therapeutics (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported that it will present clinical data from the Company’s ongoing Phase 1b studies, including updated clinical data from the study of ONT-380 in combination with trastuzumab and capecitabine ("Triplet"), and a review of the recent ASCO (Free ASCO Whitepaper) data from the ONT-380 combination with T-DM1, at today’s Corporate Update and R&D Day in New York City (Press release, Cascadian Therapeutics, JUN 14, 2016, View Source [SID:1234513293]). ONT-380 is an oral, highly selective small molecule HER2 inhibitor being studied as a combination therapy to treat HER2+ locally advanced or metastatic breast cancer, including patients with brain metastases. Schedule your 30 min Free 1stOncology Demo! "The data suggest that ONT-380, in combination with other active agents, show systemic activity in pretreated patients, supporting its advancement into later stage studies," said Erika Hamilton, MD, Director of Breast and Gynecologic Cancer Research at Sarah Cannon Research Institute. "To date, ONT-380 has shown a favorable tolerability profile and the potential to improve outcomes in patients with brain metastases. Historically, great progress has been made with the approval of HER2 targeted therapies, however, patients with metastatic disease will eventually progress and need additional therapies. A new agent that can impact both systemic and brain metastases, while not adding significant toxicities, may be a substantial benefit for patients."
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ONT-380 "Triplet" Phase 1b Data Update
The ongoing Phase 1b "Triplet" study is evaluating a combination of ONT-380 with trastuzumab and capecitabine in 27 previously treated, locally advanced or metastatic breast cancer patients with and without brain metastases. Patients had received a median of three prior HER2 directed agents: 100% with trastuzumab and T-DM1, and 74% with pertuzumab. Additionally, 41% of patients entered the trial with brain metastases.
Results from the combination trial show:
Safety Profile
Majority of adverse events were Grade 1, with most patients being able to continue on the full dose of ONT-380
Grade 3 diarrhea was infrequent, seen in 3/27 patients (11%) without a requirement for prophylactic anti-diarrheal medicine
Activity
Overall objective response rate (ORR), as defined by RECIST 1.1, of 58% (24 patients with measurable disease at baseline: 1 complete response, 13 partial responses, 6 with stable disease, 4 with progressive disease)
Interim median progression-free survival (mPFS) of 6.3 months overall (95% CI 4.1- n/a)
Patients with brain metastases
Outcomes in patients with brain metastases were similar to patients without brain metastases
"Our median PFS of 6.3 months and 58% objective response rate are promising in patients previously treated with T-DM1," commented Luke Walker, MD, Vice President of Clinical Development of Cascadian Therapeutics. "There are no true historical data with a comparable patient population given the recent changes in HER2 treatment. However, we believe a reasonable comparator is the Phase 3 TH3RESA trial of advanced HER2+ breast cancer, where patients in the control arm had a 3.3 month median PFS and 9% objective response rate. These patients received two prior HER2 agents and were treated on study with chemotherapy and/or an anti-HER2 agent, similar to current treatment options following T-DM1. Investigators continue to remain enthusiastic about advancing our Triplet combination into later stage studies."
Next steps
An ongoing Phase 2 study, known as HER2CLIMB, is exploring the Triplet combination in a randomized, double blind, placebo-controlled setting. This trial is enrolling patients with locally advanced or metastatic HER2+ breast cancer with prior treatment with a taxane, trastuzumab, pertuzumab, and T-DM1, including patients with brain metastases. This trial is expected to enroll 180 patients across approximately 100 clinical sites in the United States, Canada, and Western Europe. The HER2CLIMB trial is designed to show a 50% improvement in median PFS, with an assumption of 4.5 months in the control arm.
Commented Scott Myers, President and CEO of Cascadian Therapeutics, "We are pleased to report these encouraging clinical data and look forward to discussing the results with investigators and regulators to determine how best to advance the ONT-380 program. We anticipate providing updated data by year-end."