Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

NCT03043313 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: SGNTUC-017NCI-2017-01107ACCRU-GI-1617P30CA015083
• Study Type: interventional
• Target: 117
• Locations: 5 countries
• Sites: 56

Brief Summary

This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-positive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body. In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.

Conditions

Metastatic Colorectal Adenocarcinoma

Keywords

HER2; ERBB2; Colorectal cancer; Seattle Genetics

Outcome Measures

Primary Outcomes (1)

• Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B

  cORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to less than (\<)1.0 centimeter (cm). PR was defined as at least a 30 percentage (%) decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameters.

  Up to 46.6 months

Secondary Outcomes (13)

• ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment

  Up to 3 months

• Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment

  Up to 64.1 months

• Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B

  Up to 64.1 months

• Overall Survival (OS) in Pooled Cohorts A+B

  Up to 71.8 months

• Number of Participants With Adverse Events (AEs): Interim Analysis

  Up to 49.3 months

Study Arms (3)

Cohort A: Tucatinib + Trastuzumab

EXPERIMENTAL

Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.

Drug: Trastuzumab; Drug: Tucatinib

Cohort B: Tucatinib + Trastuzumab

EXPERIMENTAL

Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.

Drug: Trastuzumab; Drug: Tucatinib

Cohort C: Tucatinib Monotherapy

EXPERIMENTAL

Randomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.

Drug: Tucatinib

Interventions

Trastuzumab DRUG

Given intravenously (into the vein; IV)

Also known as: Herceptin

Cohort A: Tucatinib + Trastuzumab; Cohort B: Tucatinib + Trastuzumab

Tucatinib DRUG

Given orally

Also known as: ARRY-380, ONT-380, TUKYSA

Cohort A: Tucatinib + Trastuzumab; Cohort B: Tucatinib + Trastuzumab; Cohort C: Tucatinib Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically and/or cytologically documented adenocarcinoma of the colon or rectum that is metastatic and/or unresectable
• Unless contraindicated, participants must have received and failed regimens containing the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), and an anti-PD-(L)1 therapy (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins or is MSI-High.
• Have progression of unresectable or metastatic CRC after the last systemic therapy, or be intolerant of last systemic therapy
• Have RAS wild-type in primary or metastatic tumor tissue, based on expanded RAS testing
• Willing and able to provide the most recently available tissue blocks obtained prior to treatment initiation. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor
• Have confirmed HER2-positive mCRC, as defined by having tumor tissue tested at a Clinical Laboratory Improvement Act (CLIA)-certified or International Organization for Standardization (ISO)-accredited laboratory, meeting at least one of the following criteria:
• HER2+ overexpression (3+ immunohistochemistry \[IHC\]) by an FDA-approved or Conformité Européene (CE)-marked HER2 ICH test
• HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved or CE-marked HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization \[CISH\]))
• HER2 (ERBB2) amplification by CLIA-certified or ISO-accredited next generation sequencing (NGS) sequencing assay
• Have radiographically measurable disease assessable by RECIST 1.1, with at least one site of disease that is measurable and that has not been previously irradiated; or, if the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
• Life expectancy greater than 3 months
• Have adequate hematological, hepatic, renal, coagulation, and cardiac function

You may not qualify if:

• Previous treatment with anti-HER2 targeting therapy
• Previous treatment with any systemic anticancer therapy, non-central nervous system radiation, or experimental agent within 3 weeks of first dose of study treatment
• Toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:
• Alopecia and neuropathy, which must have resolved to ≤ Grade 2
• Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely
• Anemia, which must have resolved to ≤ Grade 2
• Decreased ANC, which must have resolved to ≤ Grade 2
• Have clinically significant cardiopulmonary disease
• Have known myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment
• Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosurgery) or anticipation of need for major surgical procedure during the study
• Serious, non-healing wound, ulcer, or bone fracture
• Known to be positive for hepatitis B by surface antigen expression
• Known to have active hepatitis C infection
• Exception for participants with a documented sustained virologic response of 12 weeks
• Known to be positive for human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Seagen Inc.: lead
• National Cancer Institute (NCI): collaborator
• Academic and Community Cancer Research United: collaborator

Study Sites (56)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

Keck Medical Center / University of Southern California

Los Angeles, California, 90033, United States

Location

Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

Saint Joseph Heritage Medical Group

Santa Rosa, California, 95403, United States

Location

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, 80012, United States

Location

Lombardi Cancer Center / Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists - South Region

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists - North Region

St. Petersburg, Florida, 33705, United States

Location

Winship Cancer Institute / Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637-1470, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14203, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University / University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Northwest Cancer Specialists, P.C.

Portland, Oregon, 97227, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Tennessee Oncology-Nashville/Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology - Beaumont

Beaumont, Texas, 77702-1449, United States

Location

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410, United States

Location

Texas Oncology - McAllen

McAllen, Texas, 78503, United States

Location

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, 78240, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Providence Regional Medical Center Everett

Everett, Washington, 98201, United States

Location

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109-1023, United States

Location

Aurora Research Institute Cancer Center

Milwaukee, Wisconsin, 53215, United States

Location

Cliniques Universitaires Saint Luc

Brussels, Other, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, Other, 2650, Belgium

Location

UZ Leuven campus Gasthuisberg

Leuven, Other, 3000, Belgium

Location

Hospitalier Jean Minjoz

Besançon, Other, 25030, France

Location

Center Georges Francois Leclerc

Dijon, Other, 21000, France

Location

Hôpital Franco-Britannique - Fondation Cognacq-Jay

Levallois-Perret, Other, 92300, France

Location

Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes

Lyon, Other, 69373, France

Location

Hopital Saint-Antoine

Paris, Other, 75012, France

Location

Instituto Europeo di Oncologia

Milan, Other, 20141, Italy

Location

Niguarda Ca' Granda Hospital

Milan, Other, 20162, Italy

Location

Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara

Pisa, Other, 56126, Italy

Location

Hospital Universitario Vall d'Hebron

Barcelona, Other, 08035, Spain

Location

Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

L'Hospitalet de Llobregat, Other, 08907, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, Other, 28007, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Other, 46010, Spain

Location

Related Publications (4)

• Zhang D, Taylor A, Zhao JJ, Endres CJ, Topletz-Erickson A. Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer. Clin Pharmacokinet. 2024 Oct;63(10):1477-1487. doi: 10.1007/s40262-024-01412-0. Epub 2024 Oct 5.

  PMID: 39368039 DERIVED

• Strickler JH, Bekaii-Saab TS. A study to learn how well tucatinib plus trastuzumab works for treating participants with metastatic colorectal cancer, and how safe it is: a plain language summary of the MOUNTAINEER study. Future Oncol. 2024 Mar;20(8):409-421. doi: 10.2217/fon-2023-0676. Epub 2023 Nov 8.

  PMID: 37941353 DERIVED

• Casak SJ, Horiba MN, Yuan M, Cheng J, Lemery SJ, Shen YL, Fu W, Moore JN, Li Y, Bi Y, Auth D, Fesenko N, Kluetz PG, Pazdur R, Fashoyin-Aje LA. FDA Approval Summary: Tucatinib with Trastuzumab for Advanced Unresectable or Metastatic, Chemotherapy Refractory, HER2-Positive RAS Wild-Type Colorectal Cancer. Clin Cancer Res. 2023 Nov 1;29(21):4326-4330. doi: 10.1158/1078-0432.CCR-23-1041.

  PMID: 37318379 DERIVED

• Strickler JH, Cercek A, Siena S, Andre T, Ng K, Van Cutsem E, Wu C, Paulson AS, Hubbard JM, Coveler AL, Fountzilas C, Kardosh A, Kasi PM, Lenz HJ, Ciombor KK, Elez E, Bajor DL, Cremolini C, Sanchez F, Stecher M, Feng W, Bekaii-Saab TS; MOUNTAINEER investigators. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 2023 May;24(5):496-508. doi: 10.1016/S1470-2045(23)00150-X.

  PMID: 37142372 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Trastuzumab; tucatinib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Seagen Inc.

medinfo@seagen.com

(855) 473-2436

Study Officials

• John H Strickler

  Academic and Community Cancer Research United

  STUDY CHAIR

• Jorge Ramos, DO

  Seagen Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2017
• First Posted: February 6, 2017
• Study Start: June 23, 2017
• Primary Completion: March 28, 2022
• Study Completion: November 2, 2023
• Last Updated: November 26, 2024
• Results First Posted: April 18, 2023

Record last verified: 2024-10

Locations

US (41); ES (4); FR (5); BE (3); IT (3)