NCT02091141

Brief Summary

This multicenter, non-randomized, open-label study will evaluate the efficacy and safety of six treatment regimens in participants with advanced solid tumors for whom therapies that will convey clinical benefit are not available and/or are not suitable options per the treating physician's judgment.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
673

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2014

Longer than P75 for phase_2

Geographic Reach
1 country

60 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 17, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 19, 2014

Completed
26 days until next milestone

Study Start

First participant enrolled

April 14, 2014

Completed
9.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 24, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 24, 2023

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

July 23, 2024

Completed
Last Updated

July 23, 2024

Status Verified

June 1, 2024

Enrollment Period

9.1 years

First QC Date

March 17, 2014

Results QC Date

May 23, 2024

Last Update Submit

June 26, 2024

Conditions

Outcome Measures

Primary Outcomes (2)

  • Percentage of Participants in All Tumor-Pathway Cohorts With Overall Response, as Assessed by the Investigator

    The Objective Response Rate (ORR) is defined as the percentage of patients whose best response on or before the first occurrence of disease progression is a complete response (CR) or partial response (PR). Tumor responses were assessed by investigators using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for all arms.

    From the date of first study treatment until disease progression or death from any cause, whichever occurs first (72.1 months)

  • Percentage of Atezolizumab-Treated Participants With Tissue Tumor Mutational Burden (tTMB) ≥16 Mutations/Mb With Overall Response, as Assessed by the Independent Review Committee (IRC)

    The Objective Response Rate (ORR) is defined as the proportion of patients whose best response on or before the first occurrence of disease progression is a complete response (CR) or partial response (PR). Tumor responses were assessed by Independent Review Committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

    From the date of first study treatment until disease progression or death from any cause, whichever occurs first (68.9 months)

Secondary Outcomes (5)

  • Percentage of Participants With Disease Control

    From the date of first study treatment until disease progression or death from any cause, whichever occurs first (72.1 months)

  • Progression-Free Survival (PFS)

    From the date of first study treatment until disease progression as assessed by the investigator, or death from any cause, whichever occurs first (72.1 months)

  • Overall Survival (OS)

    87.5 months

  • Duration of Response (DoR)

    From the date of first documented response (complete response [CR] or partial response [PR]) to the time of disease progression or death from any cause, whichever occurs first (70.8 months)

  • Number of Participants With Adverse Events

    From first study treatment administration to 30 days (45 days for vismodegib, 90 days for atezolizumab) after the last dose (up to approximately 6.3 years)

Study Arms (7)

Trastuzumab Plus Pertuzumab

EXPERIMENTAL

Participants will receive trastuzumab 8 milligrams per kilogram (mg/kg) intravenous (IV) infusion as loading dose, followed by 6 mg/kg IV infusion every 3 weeks; and pertuzumab 840 mg IV infusion as loading dose, followed by 420 mg IV infusion every 3 weeks.

Drug: TrastuzumabDrug: Pertuzumab

Atezolizumab

EXPERIMENTAL

Participants will receive atezolizumab 1200 mg IV infusion every 3 weeks.

Drug: Atezolizumab

Vemurafenib

EXPERIMENTAL

Participants will receive vemurafenib 960 mg orally twice daily (BID) in each 28-day cycle.

Drug: Vemurafenib

Vemurafenib Plus Cobimetinib

EXPERIMENTAL

Participants will receive vemurafenib 960 mg orally twice daily (BID) in each 28-day cycle; and cobimetinib 60 mg orally once daily for 21 days on and 7 days off in each 28-day cycle.

Drug: VemurafenibDrug: Cobimetinib

Vismodegib

EXPERIMENTAL

Participants will receive vismodegib 150 mg orally once daily in each 28-day cycle.

Drug: Vismodegib

Alectinib

EXPERIMENTAL

Participants will receive alectinib 600 mg orally BID in each 28-day cycle.

Drug: Alectinib

Erlotinib

EXPERIMENTAL

Participants will receive erlotinib 150 mg orally once daily in each 28-day cycle.

Drug: Erlotinib

Interventions

Trastuzumab will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.

Also known as: Herceptin
Trastuzumab Plus Pertuzumab

Pertuzumab will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.

Also known as: Perjeta
Trastuzumab Plus Pertuzumab

Erlotinib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.

Also known as: Tarceva
Erlotinib

Vemurafenib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.

Also known as: Zelboraf
VemurafenibVemurafenib Plus Cobimetinib

Cobimetinib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.

Also known as: Cotellic
Vemurafenib Plus Cobimetinib

Vismodegib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.

Also known as: Erivedge
Vismodegib

Alectinib will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.

Also known as: Alecensa
Alectinib

Atezolizumab will be administered as per the schedule specified in the respective arm, until tumor progression or occurrence of unacceptable toxicity.

Also known as: Tecentriq
Atezolizumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Life expectancy greater than or equal to (≥) 12 weeks
  • Histologically documented metastatic cancer (solid tumors, not including hematologic malignancies)
  • Participants who have received standard first-line therapy for metastatic cancer (except for the tumors for which no first-line therapy exists) and in whom a trial of targeted therapy is considered the best available treatment option. Eligible participants should not have available therapies that will convey clinical benefit and/or are not suitable options per the treating physician's judgment
  • No previous treatment with the specific assigned study drug or any other drug sharing the same target
  • Measurable disease by RECIST v1.1
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1 (For patients enrolling in the atezolizumab arm, ECOG score must be documented within 7 days prior to first treatment and confirmation of ECOG PS must be entered into the interactive web response system \[IWRS\] prior to initiation of treatment)
  • Adequate hematologic, renal, and liver function as defined by the protocol
  • If applicable, use of contraception methods or abstinence as defined by the protocol
  • Trastuzumab plus Pertuzumab
  • Molecular testing results from clinical laboratory improvement amendments (CLIA)-certified laboratories (using tissue and/or blood) demonstrating HER2 overexpression or amplification. Participants must have one of the following tumor types: biliary cancer, salivary cancer, or bladder cancer
  • a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrollment)
  • Left ventricular ejection fraction (LVEF) greater than (\>) 50 percent (%) or above the lower limit of the institutional normal range, whichever is lower
  • Availability of an archival or new pre-treatment tissue sample is required if molecular testing was not performed by Foundation Medicine. Any available tumor tissue sample can be submitted. The tissue sample must be submitted within 4 weeks after enrollment
  • Erlotinib
  • Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating epidermal growth factor receptor (EGFR)-activating mutations
  • +11 more criteria

You may not qualify if:

  • Participants with hematologic malignancies
  • Concurrent administration of any other anti-cancer therapy (except male participants with prostate cancer receiving androgen blockade): Bisphosphonates and denosumab are allowed; Most recent anti-cancer therapy ≤28 days and have not recovered from the side effects, excluding alopecia; Radiation therapy within ≤14 days
  • Active or untreated brain metastases
  • History of carcinomatous meningitis
  • Uncontrolled concurrent malignancy (early stage is allowed if not requiring active therapy or intervention)
  • Pregnant or breastfeeding women, or intending to become pregnant during the study
  • Any significant cardiovascular events within 6 months prior to study entry
  • Pulmonary embolism within 30 days prior to study entry
  • History or presence of clinically significant ventricular or atrial dysrhythmia \>Grade 2 per NCI CTCAE v4.0
  • Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
  • Trastuzumab plus Pertuzumab
  • Previous treatment with any HER2-targeted therapy
  • Erlotinib
  • Non-small cell lung cancer (NSCLC) or pancreatic cancer identified by exon 19 deletions or exon 21 L858R substitution mutations
  • +53 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (60)

Western Regional Medical Center at Cancer Treatment Centers of America

Goodyear, Arizona, 85338, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85259, United States

Location

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

Science 37, Inc

Culver City, California, 90230, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Moores UCSD Cancer Center; Dept Clinical Trials Office

La Jolla, California, 92093-0698, United States

Location

Eisenhower Medical Center

Rancho Mirage, California, 92270, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

Kaiser Permanente - Vallejo

Vallejo, California, 94589, United States

Location

University of Colorado

Aurora, Colorado, 80045-2517, United States

Location

SCRI Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Florida Hospital Cancer Inst; Memorial System Onc Clin Rsch

Orlando, Florida, 32804, United States

Location

Florida Cancer Specialist, North Region

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists, Research Department

West Palm Beach, Florida, 33401, United States

Location

University Cancer & Blood Center, LLC; Research

Athens, Georgia, 30607, United States

Location

Northeast Georgia Medical Center; Oncology Research Dept-5C

Gainesville, Georgia, 30501, United States

Location

Southeastern Regional Medical Center, Inc.

Newnan, Georgia, 30265, United States

Location

Northwestern University; Robert H. Lurie Comp Can Ctr; Northwestern Medicine Development Inst

Chicago, Illinois, 60611, United States

Location

University Of Chicago Medical Center; Section Of Hematology/Oncology

Chicago, Illinois, 60637, United States

Location

Midwestern Regional Med Center

Zion, Illinois, 60099, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Mayo Foundation

Rochester, Minnesota, 55905, United States

Location

Research Medical Center - Antibiotic Research Associates, Inc.

Kansas City, Missouri, 64132, United States

Location

Memorial Sloan Kettering - Monmouth

Middletown, New Jersey, 07748, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

University of New Mexico Comprehensive Cancer Center - Albuquerque Cedar Street; Drug Shipment

Albuquerque, New Mexico, 87106, United States

Location

University of New Mexico Comprehensive Cancer Center - Albuquerque Lang NE; Drug Shipment

Albuquerque, New Mexico, 87109, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Memorial Sloan Kettering Cancer Center at Westchester

Harrison, New York, 10604, United States

Location

Weill Cornell Univ Medical Ctr; Breast Cancer Center

New York, New York, 10021, United States

Location

Herbert Irving Comprehensive Cancer Center; Herbert Irving Pavillion

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Univ No Carolina School of Med; Physicians Office Bldg

Chapel Hill, North Carolina, 27599-7305v, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest Univ Health Svcs; Internal Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58102, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Eastern Regional Medical Ctr

Philadelphia, Pennsylvania, 19124, United States

Location

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Abington Mem Hosp-Abington; Rose. Can Ctr,Gyn Onc Ins

Willow Grove, Pennsylvania, 19090, United States

Location

Sanford Cancer Cnt Onco Clinic

Sioux Falls, South Dakota, 57104, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

West Clinic

Germantown, Tennessee, 38138, United States

Location

Tennessee Cancer Specialists

Knoxville, Tennessee, 37920, United States

Location

Tennessee Oncology - Nashville

Nashville, Tennessee, 37203, United States

Location

Vanderbilt Ingram Cancer Clinic

Nashville, Tennessee, 37232, United States

Location

The Center for Cancer and Blood Disorders - Fort Worth

Fort Worth, Texas, 76104, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23229, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (6)

  • Sweeney CJ, Hainsworth JD, Bose R, Burris HA, Kurzrock R, Swanton C, Friedman CF, Spigel DR, Szado T, Schulze K, Price R, Malato J, Lo AA, Levy J, Wang Y, Yu W, Meric-Bernstam F. MyPathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab + Trastuzumab Treatment of a Tissue-Agnostic Cohort of Patients With Human Epidermal Growth Factor Receptor 2-Altered Advanced Solid Tumors. J Clin Oncol. 2024 Jan 20;42(3):258-265. doi: 10.1200/JCO.22.02636. Epub 2023 Oct 4.

  • Narita Y, Yoshimoto T, Namai T, Asakawa T, Kawakami S, Gower-Page C, Reyes-Rivera I, Patel A, Nakamura Y. Pertuzumab Plus Trastuzumab for Treatment-Refractory HER2-Amplified Metastatic Colorectal Cancer: Comparison of the MyPathway Trial With a Real-World External Control Arm. JCO Clin Cancer Inform. 2022 May;6:e2200022. doi: 10.1200/CCI.22.00022.

  • Friedman CF, Hainsworth JD, Kurzrock R, Spigel DR, Burris HA, Sweeney CJ, Meric-Bernstam F, Wang Y, Levy J, Grindheim J, Shames DS, Schulze K, Patel A, Swanton C. Atezolizumab Treatment of Tumors with High Tumor Mutational Burden from MyPathway, a Multicenter, Open-Label, Phase IIa Multiple Basket Study. Cancer Discov. 2022 Mar 1;12(3):654-669. doi: 10.1158/2159-8290.CD-21-0450.

  • Javle M, Borad MJ, Azad NS, Kurzrock R, Abou-Alfa GK, George B, Hainsworth J, Meric-Bernstam F, Swanton C, Sweeney CJ, Friedman CF, Bose R, Spigel DR, Wang Y, Levy J, Schulze K, Cuchelkar V, Patel A, Burris H. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021 Sep;22(9):1290-1300. doi: 10.1016/S1470-2045(21)00336-3. Epub 2021 Jul 30.

  • Meric-Bernstam F, Hurwitz H, Raghav KPS, McWilliams RR, Fakih M, VanderWalde A, Swanton C, Kurzrock R, Burris H, Sweeney C, Bose R, Spigel DR, Beattie MS, Blotner S, Stone A, Schulze K, Cuchelkar V, Hainsworth J. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2019 Apr;20(4):518-530. doi: 10.1016/S1470-2045(18)30904-5. Epub 2019 Mar 8.

  • Hainsworth JD, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel DR, Sweeney C, Burris H, Bose R, Yoo B, Stein A, Beattie M, Kurzrock R. Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study. J Clin Oncol. 2018 Feb 20;36(6):536-542. doi: 10.1200/JCO.2017.75.3780. Epub 2018 Jan 10.

MeSH Terms

Conditions

NeoplasmsBiliary Tract NeoplasmsUrinary Bladder Neoplasms

Interventions

TrastuzumabpertuzumabErlotinib HydrochlorideVemurafenibcobimetinibHhAntag691alectinibatezolizumab

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteBiliary Tract DiseasesDigestive System DiseasesUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsSulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsIndoles

Results Point of Contact

Title
Medical Communications
Organization
Genentech, Inc.

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

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

Study Record Dates

First Submitted

March 17, 2014

First Posted

March 19, 2014

Study Start

April 14, 2014

Primary Completion

May 24, 2023

Study Completion

May 24, 2023

Last Updated

July 23, 2024

Results First Posted

July 23, 2024

Record last verified: 2024-06

Data Sharing

IPD Sharing
Will share

For eligible studies, qualified researchers may request access to individual patient-level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

Locations