Product Pipeline

Tucatinib (ONT-380)

> Small molecule
> Selective HER2 inhibitor
> Phase 2 trial underway
> HER2+ breast cancer
 

Overview

Tucatinib (ONT-380) (previously known as ARRY-380) is a small molecule selective inhibitor of HER2, a growth factor receptor that is over-expressed in multiple cancers, including breast, ovarian, and stomach cancer. HER2 mediates cell growth, differentiation and survival, and tumors that overexpress HER2 are more aggressive and historically have been associated with poorer overall survival compared with HER2-negative cancers. For additional information on the role of HER signaling in cancer, please click the About HER2 tab above.

Tucatinib is the only HER2-selective small molecule in clinical development. Other small molecule inhibitors of HER2 that are currently either approved or in development for treatment of HER2+ breast cancer are dual inhibitors of both HER1 (also known as epidermal growth factor receptor or EGFR) and HER2, including Tykerb® (lapatinib), neratinib and Gilotrif® (afatinib). Tucatinib selectively inhibits HER2 without significant inhibition of EGFR, resulting in highly potent inhibition of HER2 while avoiding the side effects associated with dual inhibitors, including skin rash and GI toxicities. Cascadian Therapeutics is currently conducting a Phase 2 trial of tucatinib in women with HER2+ breast cancer.

Tucatinib is highly active as a single agent and in combination with both chemotherapy and Herceptin® (trastuzumab) in preclinical mouse tumor models of HER2+ breast cancer, including models of brain metastases that were refractory to Tykerb (lapatinib) or neratinib treatment. In a Phase 1 single agent clinical study, tucatinib administered orally twice a day demonstrated anti-tumor activity in heavily pre-treated HER2+ breast cancer patients with metastatic disease without treatment-related Grade 3 diarrhea and only minimal Grade 3 rash. This safety and tolerability profile is important given that HER2 inhibitors are typically used in combination with other agents that may be associated with significant side effects. Addition of tucatinib to these regimens has the potential to increase efficacy without adding significantly to the side effect burden. Based on these properties, Cascadian Therapeutics believes that tucatinib is well positioned to address the unmet needs in HER2+ breast cancer.

Cascadian Therapeutics has an exclusive license from Array BioPharma Inc. to manufacture, develop and commercialize tucatinib.

Clinical Need

Approximately 20% of breast cancers overexpress HER2. Tumors with HER2 overexpression are more aggressive and historically have been associated with poorer overall survival compared with HER2-negative cancers. Therapies that target HER2 with either antibodies or small molecules have been shown to improve both progression free and overall survival. However, despite these improvements, up to a quarter of all patients treated with anti-HER2 therapy in the adjuvant setting eventually relapse and most patients with metastatic breast cancer will eventually experience disease progression.

Perhaps the greatest unmet medical need since the advent of HER2 targeted therapies is the treatment and prevention of central nervous system (CNS) metastases, which occur primarily in the brain. For patients who have received trastuzumab-based therapy in the adjuvant setting, recent data suggest that the likelihood that their first relapse will occur in the CNS is increasing. Moreover, between 30% and 50% of patients with HER2+ metastatic disease will eventually develop brain metastases.

Treatment options for CNS metastases are limited. There is currently no specific treatment regimen approved for CNS disease. Treatment of CNS metastases currently consists of the use of whole brain or stereotactic radiation or surgery. Patients may also receive chemotherapy alone, or a combination of capecitabine and lapatinib, although response rates are generally low. Because tucatinib has shown activity in preclinical models of HER2+ CNS tumors, Cascadian Therapeutics's Phase 1b trials of tucatinib are specifically designed to obtain preliminary evidence of activity in patients with CNS metastases from HER2+ breast cancer.

About HER2

HER2 is a member of a protein family that comprises four related receptor tyrosine kinases. The other family members are HER1 (also known as epidermal growth factor receptor, or EGFR), HER3 and HER4. While specific proteins (known as ligands) activate HER1, HER3, and HER4, there are no known ligands for HER2. Activation of HER2 may occur due to mutation or by interaction with other HER family members (heterodimerization) that are ligand activated.

HER2-targeted therapy using either antibody-based therapy or a small molecule tyrosine kinase inhibitor (TKI) has led to significant and ongoing improvements in disease free survival (DFS), progression free survival (PFS) and overall survival (OS) in both the adjuvant and metastatic settings. Best results have been observed when HER2 therapy is used in combination with chemotherapy. There is increasing evidence that dual targeting of HER2, either through use of two different HER2 targeted antibodies, or through use of an antibody and TKI, can lead to further improvements in efficacy.

Development Status

Cascadian Therapeutics is currently conducting a Phase 2 trial of tucatinib. This clinical trial is a Phase 2 randomized, double-blinded, placebo-controlled study of tucatinib in combination with Herceptin and Xeloda in patients with pretreated, unresectable locally advanced or metastatic HER2-positive breast cancer.

Two Phase 1b studies are now closed to enrollment. One trial is evaluating tucatinib in combination with Xeloda® (capecitabine) and/or Herceptin® (trastuzumab) in patients with HER2+ metastatic breast cancer. The other is evaluating tucatinib in combination with Kadcyla® in patients with HER2+ metastatic breast cancer. Both of these studies had options to enroll patients with central nervous system (CNS) metastases.

Clinical Data

A Phase 1b trial of tucatinib in combination with Xeloda® (capecitabine) and/or Herceptin® (trastuzumab) enrolled patients with metastatic HER2+ breast cancer with progression following prior treatment with Herceptin and Kadcyla. Patients may have received prior treatment with Perjeta and Tykerb. Patients with or without brain metastases were eligible. This trial is ongoing with patients continuing to receive treatment with tucatinib and Herceptin or tucatinib and Xeloda and Herceptin. Safety and efficacy data from this trial were presented at the SABCS in December 2014 [View Press Release | View Poster] and ASCO June 2015 [View Poster], with updated efficacy data for 41 patients presented at SABCS December 2015 [View Poster]. Overall, tucatinib in combination with Xeloda, Herceptin or Xeloda and Herceptin has been well tolerated. As reported at ASCO 2015, in a total of 32 patients treated with tucatinib 300 mg BID in combination with either Xeloda, Herceptin or Xeloda and Herceptin, the majority of adverse events were Grade 1 or 2 in severity, with no reported Grade 3 diarrhea. As reported at SABCS 2015, the objective response rate across treatment groups was 42% and CNS response rate was 33%. Based on the interim results observed results to date, we announced plans in December 2015 for a Phase 2 randomized, placebo controlled trial of tucatinib vs placebo in combination with Xeloda and Herceptin in patients with advanced HER2+ breast cancer with or without brain mets and progression following prior treatment with Herceptin, a taxane, Perjeta and Kadcyla. This study was opened to enrollment in January 2016.

A Phase 1b trial of tucatinib in combination with T-DM1 enrolled patients with metastatic HER2+ breast cancer with progression following prior treatment with trastuzumab and a taxane. Patients may have received prior treatment with pertuzumab and lapatinib. Patients with or without brain metastases were eligible. This trial has completed enrollment, but is ongoing with patients continuing to receive treatment with tucatinib and Kadcyla. Clinical data from this trial were presented at the SABCS in December 2014 [View Press Release | View Poster], and 2015 [View Poster], and ASCO June 2015 [View Press Release | View Poster]. Overall, the combination of tucatinib + Kadcyla was clinically well tolerated in 50 patients treated at the maximum tolerated dose of tucatinib, with the majority of adverse events either Grade 1 or Grade 2 in severity. Grade 3 diarrhea was reported in 4% of patients. Durable (> 6months) systemic and CNS responses and disease stabilization were seen, with an objective response rate of 41% and a CNS response rate of 33%.

The first in human Phase 1 trial, with both dose-escalation and expansion components, enrolled a total of 50 patients, 43 of whom had HER2+ metastatic breast cancer. Key findings from this study were:

  • tucatinib demonstrated an acceptable safety profile; treatment-related adverse events were primarily Grade 1.
  • There was a low incidence and severity of treatment-related diarrhea, rash and fatigue, side effects that have been associated with EGFR inhibition.
    • A single patient experienced Grade 2 treatment-related diarrhea and no patient developed treatment-related Grade 3 diarrhea; one patient had a treatment-related Grade 3 rash. Additionally, there were no treatment-related cardiac events or Grade 4 treatment-related adverse events reported.
  • The maximum tolerated dose of tucatinib established in this Phase 1 trial was 600 mg twice daily. The dose-limiting toxicity was reversible elevation in liver enzymes.

Key findings from the 22 HER2+ breast cancer patients with measurable disease treated with tucatinib at doses greater than or equal to 600 mg BID (twice daily) were:

  • The clinical benefit rate (partial response [n = 3] plus stable disease for at least 6 months [n = 3]) was 27% in this heavily pretreated patient population.
  • Notably, two of the patients with partial responses during treatment with tucatinib had confirmed progressions while on prior lapatinib- and trastuzumab-containing regimens.

Clinical Trials

The following clinical trial is currently open for enrollment:

Phase 2 Randomized, Double-Blinded, Controlled Study of tucatinib vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma

This clinical trial is a Phase 2 randomized, double-blinded, placebo-controlled study of tucatinib in combination with Herceptin and Xeloda in patients with pretreated, unresectable locally advanced or metastatic HER2-positive breast cancer. (ClinicalTrials.gov Identifier: NCT02614794)

Patients must have been previously treated with a taxane, Herceptin, Perjeta (pertuzumab) and Kadcyla (ado-trastuzumab emtansine or T-DM1). Patients with or without brain metastases are eligible, including patients with asymptomatic untreated brain metastases not needing immediate local therapy and patients with previously treated brain metastases.

The trial's objectives are to assess the efficacy, safety and pharmacokinetics of tucatinib in combination with Herceptin and Xeloda. The primary endpoint is progression free survival (PFS) based on assessment of both CNS and non-CNS disease. Additional endpoints include time to CNS progression, objective response rate and overall survival. The trial is expected to enroll approximately 180 patients in multiple centers located in the United States, Canada and Western Europe.

For more information, please visit clinicaltrials.gov.

In addition to the Cascadian Therapeutics-sponsored trial, researchers at the Dana-Farber Cancer Institute are conducting a Phase 1 trial of tucatinib in combination with Herceptin in women with brain metastases from HER2+ breast cancer (NCT01921335).

The following Cascadian Therapeutics clinical trials are ongoing but closed to further enrollment:

A Phase 1b, Open-label Study to Assess the Safety and Tolerability of tucatinib Combined with Capecitabine and Trastuzumab, Alone and in Combination in HER2+ Metastatic Breast Cancer (NCT02025192)

A Phase 1b, Open-label Study to Assess the Safety and Tolerability of tucatinib Combined With Ado-trastuzumab Emtansine (Trastuzumab Emtansine;T-DM1) (NCT01983501)

Presentations

A Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib (ONT-380) vs. Placebo in Combination with Capecitabine and Trastuzumab in Patients with Pretreated HER2+ Unresectable Locally Advanced or Metastatic Breast Carcinoma (HER2CLIMB)

San Antonio Breast Cancer Symposium, December 2016. Program OT1-02-09

Download Poster » 417KB


Efficacy Results of a Phase 1b Study of Tucatinib (ONT-380), an Oral HER2-Specific Inhibitor, in Combination With Capecitabine and Trastuzumab in HER2+ Metastatic Breast Cancer, Including Patients with Brain Metastases

San Antonio Breast Cancer Symposium, December 2016. Abstract P4-21-01

Download Poster » 533KB


Cutaneous Responses in HER2+ Metastatic Breast Cancer in Phase 1b Study of Tucatinib (ONT-380), an Oral HER2 Specific Inhibitor in Combination with Capecitabine and/or Trastuzumab in Third Line or Later Treatment

European Society of Medical Oncology (ESMO) 2016 Congress. Poster 278

Download Poster » 720KB


A Phase 2 Randomized, Double-Blinded, Placebo-Controlled Study of Tucatinib (ONT-380) vs. Placebo in Combination with Capecitabine and Trastuzumab in Patients with Pretreated HER2+ Unresectable Locally Advanced or Metastatic Breast Carcinoma

European Society of Medical Oncology (ESMO) 2016 Congress. Poster 312

Download Poster » 116KB


NS-penetrant TKI, in combination with T-DM1 in HER2+ metastatic breast cancer (MBC), including patients (pts) with brain metastases.

American Society of Clinical Oncology Annual Meeting, June 2016. Abstract 513

Download Poster » 223KB


A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with ado trastuzumab emtansine (T DM1), in HER2+ metastatic breast cancer (MBC)

San Antonio Breast Cancer Symposium, December 2015. Abstract P4-14-20

Download Poster » 207KB


ONT-380 in the treatment of HER2+ breast cancer central nervous system (CNS) metastases (mets)

San Antonio Breast Cancer Symposium, December 2015. Abstract P4-14-20

Download Poster » 1.48MB


A Phase 1b Study of ONT-380, an Oral HER2-Specific Inhibitor, in Combination with Capecitabine (C) and Trastuzumab (T) in 3rd line+ Treatment of HER2+ Metastatic Breast Cancer (MBC)

American Society of Clinical Oncology Annual Meeting, May 2015. Abstract 602

Download Poster » 357KB


ONT-380 in the Treatment of HER2+ Breast Cancer Central Nervous System (CNS) Metastases (Mets)

American Society of Clinical Oncology Annual Meeting, May 2015. Abstract 612

Download Poster » 625KB


A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with capecitabine and/or trastuzumab, in HER2+ metastatic breast cancer (MBC)

San Antonio Breast Cancer Symposium, December 2014. Poster P4-15-19

Download Poster » 678KB


A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with ado-trastuzumab (T-DM1), in HER2+ metastatic breast cancer (MBC)

San Antonio Breast Cancer Symposium, December 2014. Poster P5-15-08

Download Poster » 641KB


A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with ado-trastuzumab emtansine (T-DM1), in HER2+ metastatic breast cancer (MBC)

American Society of Clinical Oncology Annual Meeting, June 2014. Abstract TPS662

Download Poster » 310KB


A phase 1b study of ONT-380, an oral ONT HER2-specific inhibitor, combined with capecitabine and trastuzumab, in HER2+ metastatic breast cancer (MBC)

American Society of Clinical Oncology Annual Meeting, June 2014. Abstract TPS663

Download Poster » 494KB


ONT-380 (ARRY-380) - An Oral HER2 Inhibitor - Final Phase 1 Results and Conclusions

American Association for Cancer Research Special Conference on Advances in Breast Cancer Research, October, 2013

Download Poster » 1.31MB

Earlier posters regarding ONT-380 (ARRY-380) can be found on Array Biopharma's website »

Overview

Tucatinib (ONT-380) (previously known as ARRY-380) is a small molecule selective inhibitor of HER2, a growth factor receptor that is over-expressed in multiple cancers, including breast, ovarian, and stomach cancer. HER2 mediates cell growth, differentiation and survival, and tumors that overexpress HER2 are more aggressive and historically have been associated with poorer overall survival compared with HER2-negative cancers. For additional information on the role of HER signaling in cancer, please click the About HER2 tab above.

Tucatinib is the only HER2-selective small molecule in clinical development. Other small molecule inhibitors of HER2 that are currently either approved or in development for treatment of HER2+ breast cancer are dual inhibitors of both HER1 (also known as epidermal growth factor receptor or EGFR) and HER2, including Tykerb® (lapatinib), neratinib and Gilotrif® (afatinib). Tucatinib selectively inhibits HER2 without significant inhibition of EGFR, resulting in highly potent inhibition of HER2 while avoiding the side effects associated with dual inhibitors, including skin rash and GI toxicities. Cascadian Therapeutics is currently conducting a Phase 2 trial of tucatinib in women with HER2+ breast cancer.

Tucatinib is highly active as a single agent and in combination with both chemotherapy and Herceptin® (trastuzumab) in preclinical mouse tumor models of HER2+ breast cancer, including models of brain metastases that were refractory to Tykerb (lapatinib) or neratinib treatment. In a Phase 1 single agent clinical study, tucatinib administered orally twice a day demonstrated anti-tumor activity in heavily pre-treated HER2+ breast cancer patients with metastatic disease without treatment-related Grade 3 diarrhea and only minimal Grade 3 rash. This safety and tolerability profile is important given that HER2 inhibitors are typically used in combination with other agents that may be associated with significant side effects. Addition of tucatinib to these regimens has the potential to increase efficacy without adding significantly to the side effect burden. Based on these properties, Cascadian Therapeutics believes that tucatinib is well positioned to address the unmet needs in HER2+ breast cancer.

Cascadian Therapeutics has an exclusive license from Array BioPharma Inc. to manufacture, develop and commercialize tucatinib.

Clinical Need

Approximately 20% of breast cancers overexpress HER2. Tumors with HER2 overexpression are more aggressive and historically have been associated with poorer overall survival compared with HER2-negative cancers. Therapies that target HER2 with either antibodies or small molecules have been shown to improve both progression free and overall survival. However, despite these improvements, up to a quarter of all patients treated with anti-HER2 therapy in the adjuvant setting eventually relapse and most patients with metastatic breast cancer will eventually experience disease progression.

Perhaps the greatest unmet medical need since the advent of HER2 targeted therapies is the treatment and prevention of central nervous system (CNS) metastases, which occur primarily in the brain. For patients who have received trastuzumab-based therapy in the adjuvant setting, recent data suggest that the likelihood that their first relapse will occur in the CNS is increasing. Moreover, between 30% and 50% of patients with HER2+ metastatic disease will eventually develop brain metastases.

Treatment options for CNS metastases are limited. There is currently no specific treatment regimen approved for CNS disease. Treatment of CNS metastases currently consists of the use of whole brain or stereotactic radiation or surgery. Patients may also receive chemotherapy alone, or a combination of capecitabine and lapatinib, although response rates are generally low. Because tucatinib has shown activity in preclinical models of HER2+ CNS tumors, Cascadian Therapeutics's Phase 1b trials of tucatinib are specifically designed to obtain preliminary evidence of activity in patients with CNS metastases from HER2+ breast cancer.

About HER2

HER2 is a member of a protein family that comprises four related receptor tyrosine kinases. The other family members are HER1 (also known as epidermal growth factor receptor, or EGFR), HER3 and HER4. While specific proteins (known as ligands) activate HER1, HER3, and HER4, there are no known ligands for HER2. Activation of HER2 may occur due to mutation or by interaction with other HER family members (heterodimerization) that are ligand activated.

HER2-targeted therapy using either antibody-based therapy or a small molecule tyrosine kinase inhibitor (TKI) has led to significant and ongoing improvements in disease free survival (DFS), progression free survival (PFS) and overall survival (OS) in both the adjuvant and metastatic settings. Best results have been observed when HER2 therapy is used in combination with chemotherapy. There is increasing evidence that dual targeting of HER2, either through use of two different HER2 targeted antibodies, or through use of an antibody and TKI, can lead to further improvements in efficacy.

Development Status

Cascadian Therapeutics is currently conducting a Phase 2 trial of tucatinib. This clinical trial is a Phase 2 randomized, double-blinded, placebo-controlled study of tucatinib in combination with Herceptin and Xeloda in patients with pretreated, unresectable locally advanced or metastatic HER2-positive breast cancer.

Two Phase 1b studies are now closed to enrollment. One trial is evaluating tucatinib in combination with Xeloda® (capecitabine) and/or Herceptin® (trastuzumab) in patients with HER2+ metastatic breast cancer. The other is evaluating tucatinib in combination with Kadcyla® in patients with HER2+ metastatic breast cancer. Both of these studies had options to enroll patients with central nervous system (CNS) metastases.

Clinical Data

A Phase 1b trial of tucatinib in combination with Xeloda® (capecitabine) and/or Herceptin® (trastuzumab) enrolled patients with metastatic HER2+ breast cancer with progression following prior treatment with Herceptin and Kadcyla. Patients may have received prior treatment with Perjeta and Tykerb. Patients with or without brain metastases were eligible. This trial is ongoing with patients continuing to receive treatment with tucatinib and Herceptin or tucatinib and Xeloda and Herceptin. Safety and efficacy data from this trial were presented at the SABCS in December 2014 [View Press Release | View Poster] and ASCO June 2015 [View Poster], with updated efficacy data for 41 patients presented at SABCS December 2015 [View Poster]. Overall, tucatinib in combination with Xeloda, Herceptin or Xeloda and Herceptin has been well tolerated. As reported at ASCO 2015, in a total of 32 patients treated with tucatinib 300 mg BID in combination with either Xeloda, Herceptin or Xeloda and Herceptin, the majority of adverse events were Grade 1 or 2 in severity, with no reported Grade 3 diarrhea. As reported at SABCS 2015, the objective response rate across treatment groups was 42% and CNS response rate was 33%. Based on the interim results observed results to date, we announced plans in December 2015 for a Phase 2 randomized, placebo controlled trial of tucatinib vs placebo in combination with Xeloda and Herceptin in patients with advanced HER2+ breast cancer with or without brain mets and progression following prior treatment with Herceptin, a taxane, Perjeta and Kadcyla. This study was opened to enrollment in January 2016.

A Phase 1b trial of tucatinib in combination with T-DM1 enrolled patients with metastatic HER2+ breast cancer with progression following prior treatment with trastuzumab and a taxane. Patients may have received prior treatment with pertuzumab and lapatinib. Patients with or without brain metastases were eligible. This trial has completed enrollment, but is ongoing with patients continuing to receive treatment with tucatinib and Kadcyla. Clinical data from this trial were presented at the SABCS in December 2014 [View Press Release | View Poster], and 2015 [View Poster], and ASCO June 2015 [View Press Release | View Poster]. Overall, the combination of tucatinib + Kadcyla was clinically well tolerated in 50 patients treated at the maximum tolerated dose of tucatinib, with the majority of adverse events either Grade 1 or Grade 2 in severity. Grade 3 diarrhea was reported in 4% of patients. Durable (> 6months) systemic and CNS responses and disease stabilization were seen, with an objective response rate of 41% and a CNS response rate of 33%.

The first in human Phase 1 trial, with both dose-escalation and expansion components, enrolled a total of 50 patients, 43 of whom had HER2+ metastatic breast cancer. Key findings from this study were:

  • tucatinib demonstrated an acceptable safety profile; treatment-related adverse events were primarily Grade 1.
  • There was a low incidence and severity of treatment-related diarrhea, rash and fatigue, side effects that have been associated with EGFR inhibition.
    • A single patient experienced Grade 2 treatment-related diarrhea and no patient developed treatment-related Grade 3 diarrhea; one patient had a treatment-related Grade 3 rash. Additionally, there were no treatment-related cardiac events or Grade 4 treatment-related adverse events reported.
  • The maximum tolerated dose of tucatinib established in this Phase 1 trial was 600 mg twice daily. The dose-limiting toxicity was reversible elevation in liver enzymes.

Key findings from the 22 HER2+ breast cancer patients with measurable disease treated with tucatinib at doses greater than or equal to 600 mg BID (twice daily) were:

  • The clinical benefit rate (partial response [n = 3] plus stable disease for at least 6 months [n = 3]) was 27% in this heavily pretreated patient population.
  • Notably, two of the patients with partial responses during treatment with tucatinib had confirmed progressions while on prior lapatinib- and trastuzumab-containing regimens.
Clinical Trials

The following clinical trial is currently open for enrollment:

Phase 2 Randomized, Double-Blinded, Controlled Study of tucatinib vs Placebo in Combination With Capecitabine and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma

This clinical trial is a Phase 2 randomized, double-blinded, placebo-controlled study of tucatinib in combination with Herceptin and Xeloda in patients with pretreated, unresectable locally advanced or metastatic HER2-positive breast cancer. (ClinicalTrials.gov Identifier: NCT02614794)

Patients must have been previously treated with a taxane, Herceptin, Perjeta (pertuzumab) and Kadcyla (ado-trastuzumab emtansine or T-DM1). Patients with or without brain metastases are eligible, including patients with asymptomatic untreated brain metastases not needing immediate local therapy and patients with previously treated brain metastases.

The trial's objectives are to assess the efficacy, safety and pharmacokinetics of tucatinib in combination with Herceptin and Xeloda. The primary endpoint is progression free survival (PFS) based on assessment of both CNS and non-CNS disease. Additional endpoints include time to CNS progression, objective response rate and overall survival. The trial is expected to enroll approximately 180 patients in multiple centers located in the United States, Canada and Western Europe.

For more information, please visit clinicaltrials.gov.

In addition to the Cascadian Therapeutics-sponsored trial, researchers at the Dana-Farber Cancer Institute are conducting a Phase 1 trial of tucatinib in combination with Herceptin in women with brain metastases from HER2+ breast cancer (NCT01921335).

The following Cascadian Therapeutics clinical trials are ongoing but closed to further enrollment:

A Phase 1b, Open-label Study to Assess the Safety and Tolerability of tucatinib Combined with Capecitabine and Trastuzumab, Alone and in Combination in HER2+ Metastatic Breast Cancer (NCT02025192)

A Phase 1b, Open-label Study to Assess the Safety and Tolerability of tucatinib Combined With Ado-trastuzumab Emtansine (Trastuzumab Emtansine;T-DM1) (NCT01983501)

Presentations

A Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib (ONT-380) vs. Placebo in Combination with Capecitabine and Trastuzumab in Patients with Pretreated HER2+ Unresectable Locally Advanced or Metastatic Breast Carcinoma (HER2CLIMB)

San Antonio Breast Cancer Symposium, December 2016. Program OT1-02-09

Download Poster » 417KB


Efficacy Results of a Phase 1b Study of Tucatinib (ONT-380), an Oral HER2-Specific Inhibitor, in Combination With Capecitabine and Trastuzumab in HER2+ Metastatic Breast Cancer, Including Patients with Brain Metastases

San Antonio Breast Cancer Symposium, December 2016. Abstract P4-21-01

Download Poster » 533KB


Cutaneous Responses in HER2+ Metastatic Breast Cancer in Phase 1b Study of Tucatinib (ONT-380), an Oral HER2 Specific Inhibitor in Combination with Capecitabine and/or Trastuzumab in Third Line or Later Treatment

European Society of Medical Oncology (ESMO) 2016 Congress. Poster 278

Download Poster » 720KB


A Phase 2 Randomized, Double-Blinded, Placebo-Controlled Study of Tucatinib (ONT-380) vs. Placebo in Combination with Capecitabine and Trastuzumab in Patients with Pretreated HER2+ Unresectable Locally Advanced or Metastatic Breast Carcinoma

European Society of Medical Oncology (ESMO) 2016 Congress. Poster 312

Download Poster » 116KB


NS-penetrant TKI, in combination with T-DM1 in HER2+ metastatic breast cancer (MBC), including patients (pts) with brain metastases.

American Society of Clinical Oncology Annual Meeting, June 2016. Abstract 513

Download Poster » 223KB


A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with ado trastuzumab emtansine (T DM1), in HER2+ metastatic breast cancer (MBC)

San Antonio Breast Cancer Symposium, December 2015. Abstract P4-14-20

Download Poster » 207KB


ONT-380 in the treatment of HER2+ breast cancer central nervous system (CNS) metastases (mets)

San Antonio Breast Cancer Symposium, December 2015. Abstract P4-14-20

Download Poster » 1.48MB


A Phase 1b Study of ONT-380, an Oral HER2-Specific Inhibitor, in Combination with Capecitabine (C) and Trastuzumab (T) in 3rd line+ Treatment of HER2+ Metastatic Breast Cancer (MBC)

American Society of Clinical Oncology Annual Meeting, May 2015. Abstract 602

Download Poster » 357KB


ONT-380 in the Treatment of HER2+ Breast Cancer Central Nervous System (CNS) Metastases (Mets)

American Society of Clinical Oncology Annual Meeting, May 2015. Abstract 612

Download Poster » 625KB


A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with capecitabine and/or trastuzumab, in HER2+ metastatic breast cancer (MBC)

San Antonio Breast Cancer Symposium, December 2014. Poster P4-15-19

Download Poster » 678KB


A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with ado-trastuzumab (T-DM1), in HER2+ metastatic breast cancer (MBC)

San Antonio Breast Cancer Symposium, December 2014. Poster P5-15-08

Download Poster » 641KB


A phase 1b study of ONT-380, an oral HER2-specific inhibitor, combined with ado-trastuzumab emtansine (T-DM1), in HER2+ metastatic breast cancer (MBC)

American Society of Clinical Oncology Annual Meeting, June 2014. Abstract TPS662

Download Poster » 310KB


A phase 1b study of ONT-380, an oral ONT HER2-specific inhibitor, combined with capecitabine and trastuzumab, in HER2+ metastatic breast cancer (MBC)

American Society of Clinical Oncology Annual Meeting, June 2014. Abstract TPS663

Download Poster » 494KB


ONT-380 (ARRY-380) - An Oral HER2 Inhibitor - Final Phase 1 Results and Conclusions

American Association for Cancer Research Special Conference on Advances in Breast Cancer Research, October, 2013

Download Poster » 1.31MB

Earlier posters regarding ONT-380 (ARRY-380) can be found on Array Biopharma's website »