A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response

NCT04632992 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ML42439
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 38

Brief Summary

This is a Phase II, multicenter, non-randomized, open-label, multi-arm study designed to evaluate the safety and efficacy of targeted therapies as single agents or in rational, specified combinations in participants with advanced unresectable or metastatic solid tumors determined to harbor specific biomarkers. Patients will be enrolled based on local testing performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited diagnostic laboratory. The multi-arm structure of the MyTACTIC study allows patients with solid tumors to be treated with a drug or drug regimen tailored to their biomarker identified at screening.

Conditions

Advanced Unresectable or Metastatic Solid Malignancy

Outcome Measures

Primary Outcomes (1)

• Confirmed Objective Response Rate (ORR) Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Primary Central Nervous System (CNS) Tumors

  Confirmed objective response rate (cORR)=percentage of participants with best response as complete response (CR) or partial response (PR) for measurable disease \& CR for non-measurable disease. Confirmation=CR/PR on 2 consecutive visits ≥4 weeks apart for 3-week cycles \& ≥6 weeks apart for 4-week cycles. Per RECIST, CR=disappearance of all target lesions. PR= ≥30% decrease in sum of diameters of target lesions, in absence of CR. Per RANO, CR=complete disappearance of all measurable \& non-measurable disease for ≥4 weeks; no new lesions/abnormality on T2/FLAIR imaging; stable/improved non-enhancing lesions; participants must be off corticosteroids or on physiological doses; clinical status stable/improved. PR= ≥50% decrease in the sum of products of perpendicular diameters of measurable enhancing lesions on T2/FLAIR imaging for ≥4 weeks; no progression of non-measurable T1 disease; stable/improved non-enhancing lesions; corticosteroid dose ≤ baseline; clinical status stable/improved.

  Up to 32 months

Secondary Outcomes (5)

• Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria

  Time from start of treatment to the first occurrence of disease progression or death from any cause (Up to 32 months)

• Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 or RANO Criteria

  Time from the date of the first confirmed CR/PR to PD or death from any cause (Up to 32 months)

• PFS Rate at Month 3, 6, 9, and 12 as Determined by the Investigator According to RECIST v1.1 or RANO Criteria

  At Months 3, 6, 9 and 12

• Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria

  Up to 32 months

• Number of Participants With at Least One Adverse Event (AE) and Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0)

  From initiation of study drug until 28 days after the final dose of study drugs other than atezolizumab and until 90 days after the final dose of atezolizumab (Up to 32 months)

Study Arms (15)

Arm A: Entrectinib

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for ROS1 gene fusion.

Drug: Entrectinib

Arm B: Inavolisib

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.

Drug: Inavolisib

Arm C: Alectinib

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for ALK rearrangement tumors.

Drug: Alectinib

Arm D: Ipatasertib

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for either AKT1/2/3 activating mutation or PTEN loss/loss of function.

Drug: Ipatasertib

Arm E: Atezolizumab + Investigator's Choice of Chemotherapy

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for either tumor mutational burden (TMB) high or microsatellite instability (MSI) high/deficient mismatch repair (dMMR).

Drug: Atezolizumab; Drug: Investigator's Choice of Chemotherapy

Arm F: Trastuzumab Emtansine + Atezolizumab

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for human epidermal growth factor receptor 2 (HER2) mutations or amplification without known TMB high or MSI high/dMMR.

Drug: Atezolizumab; Drug: Trastuzumab Emtansine

Arm G: PH FDC SC

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.

Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf

Arm H: PH FDC SC + Investigator's Choice of Chemotherapy

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.

Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf; Drug: Investigator's Choice of Chemotherapy

Arm I: Trastuzumab Emtansine + Tucatinib

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for HER2 mutation or amplification without known TMB high or MSI high/dMMR.

Drug: Trastuzumab Emtansine; Drug: Tucatinib

Arm J: Trastuzumab Emtansine + Atezolizumab

EXPERIMENTAL

Participants in this treatment arm must have positive tumor biomarker results for HER2 mutation or amplification and TMB high or MSI high/dMMR.

Drug: Atezolizumab; Drug: Trastuzumab Emtansine

Arm K: Ipatasertib + Atezolizumab

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.

Drug: Ipatasertib; Drug: Atezolizumab

Arm L: Ipatasertib + Atezolizumab

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for either AKT1/2/3 activating mutation or PTEN loss/loss of function.

Drug: Ipatasertib; Drug: Atezolizumab

Arm M: Ipatasertib + Paclitaxel

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker results for PI3KCA activating mutations and either AKT1/2/3 activating mutation or PTEN loss/loss of function.

Drug: Ipatasertib; Drug: Paclitaxel

Arm N: Atezolizumab + Tiragolumab

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for either TMB high or MSI high/dMMR.

Drug: Atezolizumab; Drug: Tiragolumab

Arm O: Pralsetinib

EXPERIMENTAL

Participants in this treatment arm must have a positive tumor biomarker result for RET fusion.

Drug: Pralsetinib

Interventions

Entrectinib DRUG

Entrectinib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 600 milligrams (mg) per day once a day (QD) until disease progression, intolerable toxicity, or consent withdrawal.

Also known as: Rozlytrek™, RG6268, RO7102122

Arm A: Entrectinib

Inavolisib DRUG

Inavolisib will be self-administered by participants orally at home (except on clinic days) at the same time each day, on a starting dose of 9 mg/day QD until disease progression, intolerable toxicity, or consent withdrawal.

Also known as: GDC-0077, RG6114, RO7113755

Arm B: Inavolisib

Alectinib DRUG

Alectinib will be self-administered by participants orally at home (except on clinic days), at the same times each day, on a starting dose of 600 mg twice a day (BID) until disease progression, intolerable toxicity, or consent withdrawal.

Also known as: Alecensa®, RG7853, RO5424802

Arm C: Alectinib

Ipatasertib DRUG

Ipatasertib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 400 mg QD until disease progression, intolerable toxicity, or consent withdrawal.

Also known as: GDC-0068, RG7440, RO5532961

Arm D: Ipatasertib; Arm K: Ipatasertib + Atezolizumab; Arm L: Ipatasertib + Atezolizumab; Arm M: Ipatasertib + Paclitaxel

Atezolizumab DRUG

Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg for participants on Day 1 of each 21-day cycle until unacceptable toxicity or progressive disease (or loss of clinical benefit).

Also known as: Tecentriq®, RG7446, RO5541267

Arm E: Atezolizumab + Investigator's Choice of Chemotherapy; Arm F: Trastuzumab Emtansine + Atezolizumab; Arm J: Trastuzumab Emtansine + Atezolizumab; Arm K: Ipatasertib + Atezolizumab; Arm L: Ipatasertib + Atezolizumab; Arm N: Atezolizumab + Tiragolumab

Trastuzumab Emtansine DRUG

Trastuzumab emtansine will be administered at 3.6 mg per kilogram (kg) of body weight by IV infusion every 21 days (unless dose reduction and/or dose delays are required) until disease progression or unacceptable toxicity.

Also known as: Kadcyla®, RG3502, RO5304020

Arm F: Trastuzumab Emtansine + Atezolizumab; Arm I: Trastuzumab Emtansine + Tucatinib; Arm J: Trastuzumab Emtansine + Atezolizumab

Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf DRUG

PH FDC SC will be administered subcutaneously (SC) at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab once every 3 weeks.

Also known as: PHESGO™, PH FDC SC, Fixed dose combination of trastuzumab and pertuzumab administered subcutaneously, RG6264, RO7198574

Arm G: PH FDC SC; Arm H: PH FDC SC + Investigator's Choice of Chemotherapy

Tucatinib DRUG

Tucatinib 300 mg will be administered orally BID continuously starting from Cycle 1 Day 1 onwards.

Also known as: Tukysa™

Arm I: Trastuzumab Emtansine + Tucatinib

Investigator's Choice of Chemotherapy DRUG

Chemotherapy will consist of docetaxel, paclitaxel, or capecitabine, as determined by the investigator, and will be administered per the respective package insert and institutional guidelines.

Arm E: Atezolizumab + Investigator's Choice of Chemotherapy; Arm H: PH FDC SC + Investigator's Choice of Chemotherapy

Paclitaxel DRUG

The dose of paclitaxel is 80 mg/m2 administered by IV infusion on Days 1, 8, and 15 of each 28-day cycle. The paclitaxel infusion will be delivered over at least 60 minutes for each dose per institutional guidelines and administered after the oral dose of ipatasertib.

Arm M: Ipatasertib + Paclitaxel

Tiragolumab DRUG

Following the administration of atezolizumab and an observation period, participants will receive 600 mg tiragolumab at a fixed dose administered by IV infusion on Day 1 of each 21-day cycle.

Also known as: RG6058, RO7092284, MTIG7192A

Arm N: Atezolizumab + Tiragolumab

Pralsetinib DRUG

Pralsetinib will be self-administered by participants orally at home (except on clinic days), at the same time each day, on a starting dose of 400 mg/day (four 100-mg capsules per day) once a day (QD) until disease progression, intolerable toxicity, or consent withdrawal.

Also known as: GAVRETO™, RG6396, RO7499790

Arm O: Pralsetinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited diagnostic laboratory and availability of a full report of the testing results. This may be from a tissue or blood sample.
• Evaluable or measurable disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Life expectancy ≥8 weeks
• Adequate hematologic and end-organ function, as defined in the protocol, obtained within 14 days prior to initiation of study treatment
• Agrees to take measures to prevent pregnancy in the patient or partner

You may not qualify if:

• Current participation or enrollment in another therapeutic clinical trial
• Symptomatic or actively progressing CNS metastases (asymptomatic patients with treated or untreated CNS metastases may be eligible, provided all protocol-defined criteria are met)
• History of leptomeningeal disease, unless noted otherwise for a specific treatment arm of the study
• Wide field radiotherapy within 14 days prior to start of study treatment
• Stereotactic radiosurgery within 7 days prior to start of study treatment
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact patient safety
• Receipt of any anticancer drug/biologic or investigational treatment 21 days prior to Cycle 1, Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1, Day 1 (androgen blockage may be continued for male patients with prostate cancer)
• Known human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) infection with status outside of study-allowed criteria
• History of or concurrent serious medical condition or abnormality in clinical laboratory tests that precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study
• History of malignancy other than disease under study within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment
• Major surgical procedure, other than for diagnosis, or significant traumatic injury within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or higher), myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina
• Pregnant or breastfeeding, or intending to become pregnant during the study

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (38)

Alaska Oncology and Hematology

Anchorage, Alaska, 99508, United States

Location

Arizona Clinical Research Ctr

Oro Valley, Arizona, 85755-6216, United States

Location

Genesis Cancer Center

Hot Springs, Arkansas, 71913, United States

Location

California Cancer Associates for Research and Excellence - Encinitas

Encinitas, California, 92024-1328, United States

Location

Los Angeles Hematology Oncology Medical Group

Los Angeles, California, 90017, United States

Location

Pacific Cancer Care - Monterey

Monterey, California, 93940, United States

Location

Kaiser Permanente - San Francisco Medical Center

San Francisco, California, 94118, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Kaiser Permanente Medical Ctr

Vallejo, California, 94589, United States

Location

Ventura County Hematology Oncology Specialists

Ventura, California, 93003, United States

Location

Eastern CT Hematology and Oncology Associates

Norwich, Connecticut, 06360-2740, United States

Location

SCRI Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists - NORTH - SCRI - PPDS

St. Petersburg, Florida, 33705-1400, United States

Location

Florida Cancer Specialists - PAN - SCRI - PPDS

Tallahassee, Florida, 32308, United States

Location

Florida Cancer Specialists - EAST - SCRI - PPDS

West Palm Beach, Florida, 33401-3406, United States

Location

St Luke?s Cancer Institute

Boise, Idaho, 83712, United States

Location

Hematology and Oncology Clinic

Baton Rouge, Louisiana, 70809, United States

Location

Saint Agnes Hospital - Baltimore - Hunt - PPDS

Baltimore, Maryland, 21229-5201, United States

Location

Ascension St. John Hospital

Detroit, Michigan, 48236, United States

Location

Frontier Cancer Center and Blood Institute

Billings, Montana, 59102, United States

Location

Southeast Nebraska Cancer Center

Lincoln, Nebraska, 68510-2496, United States

Location

New Jersey Hematology Oncology Associates LLC

Brick, New Jersey, 08724-3009, United States

Location

Astera Cancer Care East Brunswick

East Brunswick, New Jersey, 08816, United States

Location

Central Park Hematology and Oncology

New York, New York, 10028-0506, United States

Location

Eastchester Center for Cancer Care

The Bronx, New York, 10469, United States

Location

New York Cancer & Blood Specialists

The Bronx, New York, 10469, United States

Location

Messino Cancer Centers

Asheville, North Carolina, 28806, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Tri County Hematologyoncology

Canton, Ohio, 44718, United States

Location

SCRI Mark H. Zangmeister Center

Columbus, Ohio, 43219, United States

Location

Kaiser Permanente Center For Health Research

Portland, Oregon, 97227, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

The West Clinic, PC dba West Cancer Center

Memphis, Tennessee, 38138, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

The Center for Cancer and Blood Disorders - PPDS

Fort Worth, Texas, 76104-4611, United States

Location

Mays Cancer Center at UT Health San Antonio MD Anderson Cancer

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University - Massey Cancer Center

Richmond, Virginia, 23219, United States

Location

Northwest Medical Specialties B

Federal Way, Washington, 98003, United States

Location

Related Publications (1)

• Zuniga RM, VanderWalde A, Schwartzberg LS, Spigel DR, Passler L, Hong J, Howland M, Darbonne WC, Szado T, Daniel D. Impact of community recruitment and inclusion initiatives on enrollment in the biomarker-driven MyTACTIC trial. Future Oncol. 2026 Jan;22(1):59-69. doi: 10.1080/14796694.2025.2595690. Epub 2025 Dec 15.

  PMID: 41392942 DERIVED

MeSH Terms

Interventions

entrectinib; inavolisib; alectinib; ipatasertib; atezolizumab; Ado-Trastuzumab Emtansine; pertuzumab; Trastuzumab; tucatinib; Paclitaxel; Tiragolumab; pralsetinib

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Genentech, Inc.

  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: November 12, 2020
• First Posted: November 17, 2020
• Study Start: January 13, 2021
• Primary Completion: December 4, 2023
• Study Completion: February 27, 2024
• Last Updated: January 8, 2025
• Results First Posted: January 8, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

US (38)