Biotechnology Events

Home

Cascadian Therapeutics, Inc.

Partner : Array BioPharma

.

PLEASE SCROLL DOWN TO THE RESULTS SECTION (below) THERE IS AN ENTRY FOR THIS EVENT.

.

Oncothyreon and Array BioPharma Announce Initiation of Phase 1b Trial of ONT-380 in Combination with Capecitabine and/or Trastuzumab in Patients with Metastatic HER2+ Breast Cancer
SEATTLE AND BOULDER, CO, Feb. 3, 2014 /PRNewswire/ - Oncothyreon Inc. (NASDAQ: ONTY) and Array BioPharma Inc. (NASDAQ: ARRY) today announced the initiation of a Phase 1b trial of ONT-380 (ARRY-380) in combination with Xeloda® (capecitabine) and/or Herceptin® (trastuzumab) in patients with metastatic HER2+ breast cancer. ONT-380 is an orally active, reversible and selective small-molecule HER2 inhibitor invented by Array and being developed by Oncothyreon in collaboration with Array.

The trial (ClinicalTrials.gov Identifier NCT02025192) is a dose-escalation study in patients who have been previously treated with Herceptin® (trastuzumab) and Kadcyla® (ado-trastuzumab emtansine or TDM-1) for metastatic breast cancer. The primary objective is to determine the maximum-tolerated and/or recommended Phase 2 dose (MTD/RP2D) of ONT-380 in combination with the approved dose of either Xeloda or Herceptin or both. Secondary objectives include an evaluation of the safety and preliminary anti-tumor activity of the combinations. The study includes an expansion arm at the MTD/RP2D of ONT-380 in combination with both Xeloda and Herceptin, with the option to include expansion arms in combination with either agent alone. Patients with treated stable central nervous system (CNS) metastases are eligible for the dose escalation portions of the trial, while patients with CNS metastases which are either asymptomatic and untreated or progressive following local therapy may be included in the expansion cohorts. The trial is expected to enroll approximately 50 patients.

"The treatment or prevention of CNS metastases is perhaps the greatest unmet medical need for patients with HER2+ metastatic breast cancer," said Diana Hausman, M.D., Chief Medical Officer of Oncothyreon. "ONT-380 has demonstrated preclinical activity in an animal model of brain metastases from HER2+ breast cancer. This trial is intended to identify clinically relevant combination therapy to advance the evaluation of the activity of ONT-380 in patients with CNS metastases."

"We are encouraged by the rapid progress the Oncothyreon team has made since initiating our collaboration, now that important combination studies are enrolling," said Michael Needle, M.D., Chief Medical Officer of Array. "We believe the unique pharmacologic properties of ONT-380, as the only oral, selective HER2 inhibitor, position it favorably as a potential new option for patients fighting breast cancer."
More
Source: press release, 2/03/14. http://ir.oncothyreon.com/releasedetail.cfm?ReleaseID=822723

.

A Phase 1b, Open-label Study to Assess the Safety and Tolerability of ONT-380 Combined With Capecitabine and Trastuzumab, Alone and in Combination in HER2+ Metastatic Breast Cancer
Estimated Enrollment: 60
Study Start Date: December 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
More
Source: clinical trials.gov. http://clinicaltrials.gov/ct2/show/NCT02025192?term=ONT-380&rank=1

.

Compound/DeviceSpecialtyIndicationCompound ClassTarget
ONT-380 (ARRY-380)OncologyBreast Cancer (metastatic)HER-2 inhibitorHER-2 (ErbB-2)

Mechanism of action: ONT-380 (ARRY-380) - An orally bioavailable inhibitor of the human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity. ErbB-2 inhibitor ARRY-380 selectively binds to and inhibits the phosphorylation of ErbB-2, which may prevent the activation of ErbB-2 signal transduction pathways, resulting in growth inhibition and death of ErbB-2-expressing tumor cells. ErbB-2 is overexpressed in a variety of cancers and plays an important role in cellular proliferation and differentiation.

Phase of Development: Ib

Event Type: Data: Phase Ib trial results

Dates: 2016-05-01 - 2016-06-30

Results:

.

Cascadian Therapeutics Announces Presentations of Updated Clinical Data at the 2016 San Antonio Breast Cancer Symposium

Updated "Triplet" data to be presented at SABCS

SEATTLE, Nov. 15, 2016 (GLOBE NEWSWIRE) -- Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage biopharmaceutical company, today announced that two abstracts on the Company's lead product candidate tucatinib (also known as ONT-380) will be presented at the 2016 San Antonio Breast Cancer Symposium (SABCS) to be held December 6-10 in San Antonio, TX.

The Phase 1b "Triplet" poster presentation will include more mature progression-free survival (PFS) and safety data not included in the abstract posted on the SABCS website, which was as of May 2016.

Details of Poster Presentations:

A Phase 2 Randomized, Double-Blinded, Controlled Study of ONT-380 vs. Placebo in Combination with Capecitabine (C) and Trastuzumab (T) in Patients with Pretreated HER2+ Unresectable Locally Advanced or Metastatic Breast Carcinoma (MBC) (HER2CLIMB)
First Author: Erika Hamilton, Sarah Cannon Research Institute, Nashville, TN
Poster/Session: OT1-02-09, Ongoing Trials — Chemotherapy
Date/Time: Wednesday, December 7, 2016; 5:00 p.m.—7:00 p.m. CST

Efficacy Results of a Phase 1b Study of ONT-380, an Oral HER2-Specific Inhibitor, in Combination with Capecitabine (C) and Trastuzumab (T) in HER2+ Metastatic Breast Cancer (MBC), Including Patients (pts) with Brain Metastases (mets)
First Author: Erika Hamilton, Sarah Cannon Research Institute, Nashville, TN
Poster/Session: P4-21-01, Treatment: HER2-Targeted Therapy
Date/Time: Friday, December 9, 2016; 7:30 a.m.—9:00 a.m. CST
More
Source: press release, 11/15/16. http://ir.cascadianrx.com/releasedetail.cfm?ReleaseID=999452

.

Cascadian Therapeutics Reports Topline ONT-380 "Triplet" Data and Outlines Key Development Strategies

Company to webcast today's Research and Development Day at 2 pm Eastern

SEATTLE, June 14, 2016 (GLOBE NEWSWIRE) -- Cascadian Therapeutics (NASDAQ:CASC), a clinical-stage biopharmaceutical company, 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 data from the ONT-380 combination with T-DM1, at today's Corporate Update and R&D Day in New York City. 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.

"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."

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."

Webcast
The R&D Day presentation, scheduled to begin at 2 pm EDT today, June 14, 2016, will be webcast live and can be accessed on the "Events & Presentations" page of the "News & Events" section of Cascadian Therapeutics' website at www.cascadianrx.com.

Participants may also dial-in to hear the presentation using the following:
Participant Toll-Free Dial-In Number: (877) 280-7291
Participant International Dial-In Number: (707) 287-9361
Conference ID: 33124496

An archived version of the webcast will be available after completion of the presentation.
More
Source: press release, 6/14/16. http://ir.cascadianrx.com/releasedetail.cfm?ReleaseID=975591

.

Oncothyreon Announces Data for ONT-380 in HER2-Positive Breast Cancer Patients With and Without Brain Metastases at the San Antonio Breast Cancer Symposium

Company to Hold Conference Call to Discuss ONT-380 Data and Further Development Plans Today at 4:30 EST

SEATTLE, Dec. 08, 2015 (GLOBE NEWSWIRE) -- Oncothyreon Inc. (Nasdaq:ONTY), a clinical-stage biopharmaceutical company dedicated to the development of therapeutic products that can improve the lives and outcomes of patients with cancer, today announced updated data from the company's ongoing trials of ONT-380, an orally active, reversible and selective small-molecule HER2 inhibitor being developed for the treatment of HER2-positive metastatic breast cancer. The data will be the subject of two presentations at the San Antonio Breast Cancer Symposium (SABCS) being held December 8-12, 2015 in San Antonio, TX.

The first presentation (Abstract P4-14-20) highlights data from a Phase 1b trial of ONT-380 in combination with Kadcyla® (ado-trastuzumab emtansine or T-DM1) in patients who have previously failed treatment with Herceptin® (trastuzumab) and a taxane for HER2-positive breast cancer (ClinicalTrials.gov Identifier NCT01983501). The data demonstrate an overall response rate of 41% and a clinical benefit rate (CBR) of 59% in an advanced stage patient population, 60% of whom have a history of central nervous system (CNS) metastases. The CNS CBR for patients with response assessable CNS metastases was 64%. The second presentation (Abstract P4-14-19) combines data for patients with response assessable brain metastases from two trials, the Phase 1b trial in combination with Kadcyla and a Phase 1b trial of ONT-380 in combination with Herceptin and/or Xeloda® (capecitabine) (ClinicalTrials.gov Identifier NCT02025192). The analysis includes patients with previously untreated CNS metastases as well as patients with progressive or new CNS metastases after prior treatment with radiation or surgery. Responses and clinical benefit in the CNS were seen for both groups and in all combinations tested.

"We are pleased by the response rate and clinical benefit rate we have seen in the combination trial of ONT-380 and Kadcyla, including in patients with brain metastases," said Robert L. Kirkman, M.D., President and CEO of Oncothyreon. "In addition, the analysis of patients with response assessable brain metastases from both our trials reinforce and expand upon our previously reported results, increasing our commitment to exploring ONT-380 in this indication. Our planned Phase 2 trial of ONT-380 in combination with Xeloda and Herceptin includes significant CNS-focused endpoints. We also plan to explore additional options to develop ONT-380 in combination with Kadcyla in patients with CNS metastases."

"CNS metastases occur in up to 50 percent of women with HER2-positive metastatic breast cancer, and these patients have limited options for systemic treatment," said Stacy Moulder, M.D., Associate Professor, Section Chief of Clinical Research, Breast Medical Oncology, University of Texas MD Anderson Cancer Center. "The level of clinical activity seen in the expanded data set for ONT-380 in these advanced stage patients is encouraging and worthy of urgent further development."
More
Source: press release, 12/08/15. http://ir.oncothyreon.com/releasedetail.cfm?ReleaseID=946155

.

Dec 12, 2014

Oncothyreon Announces Presentation of Positive ONT-380 Data at San Antonio Breast Cancer Symposium

Phase 1 Data Demonstrate Preliminary Clinical Activity and Tolerability in Heavily Pretreated Patient Population

SEATTLE, Dec. 12, 2014 (GLOBE NEWSWIRE) -- Oncothyreon Inc. (Nasdaq:ONTY) today announced that positive preliminary data from two ongoing Phase 1b trials of ONT-380 (ARRY-380), an orally active, reversible and selective small molecule HER2 inhibitor, will be presented at the San Antonio Breast Cancer Symposium.

The first trial (ClinicalTrials.gov Identifier NCT02025192) is a parallel dose-escalation study of ONT-380 in combination with Xeloda® (capecitabine) and/or Herceptin® (trastuzumab) in patients previously treated with Herceptin and Kadcyla® (ado-trastuzumab emtansine or TDM-1) for metastatic breast cancer. Interim data will be presented for 21 patients, including seven in the ONT-380 plus Xeloda cohort, eight in the ONT-380 plus Herceptin cohort, four in the ONT-380 plus Xeloda and Herceptin cohort, and two in an ongoing expansion cohort in patients with untreated or progressive central nervous system (CNS) metastases, both treated with ONT-380 plus Herceptin.

Seventeen of the patients were evaluable for best overall response using RECIST 1.1 criteria. In the ONT-380 plus Xeloda cohort, four patients had a partial response (PR) and three patients had stable disease (SD), for an overall clinical benefit rate of 100 percent (defined as either PR/CR or stable disease for > 6 months). In the ONT-380 plus Herceptin cohort, best response has been a complete response (CR) in one patient, PR in two patients, SD in four patients, and progressive disease (PD) in one patient. Two patients in the ONT-380 plus Xeloda and Herceptin cohort are currently evaluable, one of whom had a PR and one PD. One patient in the CNS expansion cohort had a PR and the other SD.

Fourteen of the 21 patients in this trial had a history of CNS metastases, of whom six had evaluable target lesions per modified RECIST 1.1 at the time of entry into the trial. Of these, best initial response has been SD, with decreases in CNS target lesions in four patients. Five of these six patients remain active on study.

The second trial (ClinicalTrials.gov Identifier NCT01983501) is a dose-escalation study of ONT-380 in combination with Kadcyla in patients who have been previously treated with Herceptin and a taxane for metastatic breast cancer. Data will be presented for 17 patients, of whom 16 were evaluable for response. Patients in this trial were heavily pre-treated, having received a median of two prior systemic treatments for metastatic disease, including prior pertuzumab in six, and prior lapatinib in five. Best overall response has been PR in five patients, SD in seven patients, and PD in four patients. Nine patients in this trial had a history of CNS metastases, of whom four had measurable disease per modified RECIST 1.1 at the time of entry into the trial. Three of these four patients have SD in the CNS and remain active on the study, including two with decreases in measurable target lesions.

ONT-380 was well-tolerated in both studies and in all combinations tested. The most common adverse events included nausea and vomiting, diarrhea, fatigue and elevated liver function tests. Most adverse events were grade 1 or 2 in severity. Elevated liver function tests were more common in patients also receiving Kadcyla. No grade 3 diarrhea was seen in either trial; anti-diarrheal prophylaxis was not a study requirement.

A maximally tolerated dose (MTD) for ONT-380 has not been identified to date in any of the combinations tested in either trial. An improved tablet formulation of ONT-380 with increased absorption was used in these trials compared to the powder in capsule formulation used in the previously reported Phase 1 trial. All patients in both current trials received an initial dose of 300 mg twice per day. At that dose, measured drug levels were similar to those seen with 600 mg twice per day (the single agent MTD) of the prior formulation. Drug exposure in the current trials was well above the level needed for 90 percent inhibition of HER2.

"The preliminary signs of efficacy in both of these trials are encouraging for the further development of ONT-380," said Stacy Moulder, M.D., Associate Professor, Breast Medical Oncology, University of Texas MD Anderson Cancer Center. "These patients were heavily pre-treated, with the majority already having a history of CNS metastases. Nevertheless, meaningful responses and prolonged stable disease have been observed and many patients currently remain on study. Importantly, ONT-380 has been well-tolerated, with a toxicity profile that facilitates its combination with other agents."

"We are continuing to enroll patients in both of these Phase 1b trials," said Diana Hausman, M.D., Chief Medical Officer of Oncothyreon. "We are currently testing an increased dose level of ONT-380 of 350 mg twice daily in both trials. We are also enrolling cohorts of patients in both trials with CNS metastases from HER2+ breast cancer that are either asymptomatic and untreated or progressive following treatment to better define the potential role of ONT-380 in treating patients with this serious unmet medical need."
More
Source: press release, 12/12/14. http://ir.oncothyreon.com/releasedetail.cfm?ReleaseID=887414

.