Seagen Announces Last Patient Enrolled in Phase 2 MOUNTAINEER Trial Evaluating TUKYSA® (Tucatinib) Regimen in HER2-Positive Metastatic Colorectal Cancer
Seagen has completed patient enrollment for the Phase 2 MOUNTAINEER clinical trial, assessing TUKYSA® (tucatinib) in HER2-positive metastatic colorectal cancer patients. This trial aims to support an accelerated approval application in the U.S. Early results show promising anti-tumor activity and a favorable safety profile. The trial involves 117 patients and focuses on the objective response rate and various survival metrics, addressing a critical unmet medical need.
- Completion of patient enrollment in the Phase 2 MOUNTAINEER clinical trial for TUKYSA.
- Promising early results indicating encouraging anti-tumor activity.
- Focus on a significant unmet medical need in HER2-positive metastatic colorectal cancer.
- Dependence on the trial results to support accelerated approval, which carries inherent risks.
– Trial Designed to Support an Accelerated Approval Application in the
“Completing enrollment in the MOUNTAINEER trial is an important step toward potentially bringing this therapy to patients with HER2-positive metastatic colorectal cancer,” said
Early results from the MOUNTAINEER trial were presented at the
TUKYSA is an oral, small molecule tyrosine kinase inhibitor that is highly selective for HER2. HER2 amplification or overexpression occurs in approximately three-to-five percent of all patients with mCRC.2,3
About MOUNTAINEER
MOUNTAINEER is a
About Colorectal Cancer
Colorectal cancer is the second leading cause of cancer death in
About TUKYSA (tucatinib)
TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.
TUKYSA in combination with trastuzumab and capecitabine was approved by the
In
Warnings and Precautions
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Diarrhea – TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. In HER2CLIMB,
81% of patients who received TUKYSA experienced diarrhea, including12% with Grade 3 diarrhea and0.5% with Grade 4 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in6% of patients and discontinuation of TUKYSA in1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB.
If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
-
Hepatotoxicity – TUKYSA can cause severe hepatotoxicity. In HER2CLIMB,
8% of patients who received TUKYSA had an ALT increase >5 × ULN,6% had an AST increase >5 × ULN, and1.5% had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in8% of patients and discontinuation of TUKYSA in1.5% of patients.
Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
- Embryo-Fetal Toxicity – TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential risk to a fetus. Advise females of reproductive potential, and male patients with female partners of reproductive potential, to use effective contraception during TUKYSA treatment and for at least 1 week after the last dose.
Adverse Reactions
Serious adverse reactions occurred in
Adverse reactions led to treatment discontinuation in
The most common adverse reactions in patients who received TUKYSA (≥
Lab Abnormalities
In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥
Drug Interactions
- Strong CYP3A or Moderate CYP2C8 Inducers: Concomitant use may decrease TUKYSA activity. Avoid concomitant use of TUKYSA.
- Strong or Moderate CYP2C8 Inhibitors: Concomitant use of TUKYSA with a strong CYP2C8 inhibitor may increase the risk of TUKYSA toxicity; avoid concomitant use. Increase monitoring for TUKYSA toxicity with moderate CYP2C8 inhibitors.
- CYP3A Substrates: Concomitant use may increase the toxicity associated with a CYP3A substrate. Avoid concomitant use of TUKYSA where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP3A substrate dosage.
- P-gp Substrates: Concomitant use may increase the toxicity associated with a P-gp substrate. Consider reducing the dosage of P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicity.
Use in Specific Populations
- Lactation: Advise women not to breastfeed while taking TUKYSA and for at least 1 week after the last dose.
- Renal Impairment: Use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (CLcr < 30 mL/min), because capecitabine is contraindicated in patients with severe renal impairment.
- Hepatic Impairment: Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment.
For more information, please see the full Prescribing Information for TUKYSA here.
About
Seagen Forward-Looking Statements
Certain of the statements made in this press release are forward-looking, such as those, among others, relating to the therapeutic potential of TUKYSA, its possible efficacy, safety and therapeutic uses, the referenced Phase 2 clinical trial and the potential for data from such trial to support registration under accelerated approval regulations in
References:
- Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246.
- Takegawa N and Yonesaka K (2017). HER2 as an emerging oncotarget for colorectal cancer treatment after failure of anti-epidermal growth factor receptor therapy. Clin Colorectal Cancer 16: 247-51.
- Valtorta E., et al. Assessment of a HER2 scoring system for colorectal cancer: results from a validation study. Mod Pathol 28: 1481-91 2015.
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SEER Cancer Stat Facts: Colorectal Cancer.
National Cancer Institute .Bethesda, MD . https://seer.cancer.gov/statfacts/html/colorect.html. AccessedJuly 26, 2021 .
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Vice President, Corporate Communications
(310) 430-3476
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