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

Genentech

Status and phase

Completed

Phase 2

Conditions

Advanced Unresectable or Metastatic Solid Malignancy

Treatments

Drug: Paclitaxel

Drug: Alectinib

Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf

Drug: Investigator's Choice of Chemotherapy

Drug: Atezolizumab

Drug: Inavolisib

Drug: Pralsetinib

Drug: Ipatasertib

Drug: Trastuzumab Emtansine

Drug: Tiragolumab

Drug: Tucatinib

Drug: Entrectinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT04632992

ML42439

Details and patient eligibility

About

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.

Enrollment

252 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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
In addition to the general inclusion criteria above, there are treatment-specific inclusion criteria that apply for each respective treatment arm (as detailed in the protocol)

Exclusion criteria

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
In addition to the general exclusion criteria above, there are treatment-specific exclusion criteria that apply for each respective treatment arm (as detailed in the protocol)

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

252 participants in 15 patient groups

Arm A: Entrectinib

Experimental group

Description:

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

Treatment:

Drug: Entrectinib

Arm B: Inavolisib

Experimental group

Description:

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

Treatment:

Drug: Inavolisib

Arm C: Alectinib

Experimental group

Description:

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

Treatment:

Drug: Alectinib

Arm D: Ipatasertib

Experimental group

Description:

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.

Treatment:

Drug: Ipatasertib

Arm E: Atezolizumab + Investigator's Choice of Chemotherapy

Experimental group

Description:

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).

Treatment:

Drug: Atezolizumab

Drug: Investigator's Choice of Chemotherapy

Arm F: Trastuzumab Emtansine + Atezolizumab

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: Trastuzumab Emtansine

Arm G: PH FDC SC

Experimental group

Description:

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.

Treatment:

Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf

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

Experimental group

Description:

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.

Treatment:

Drug: Investigator's Choice of Chemotherapy

Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf

Arm I: Trastuzumab Emtansine + Tucatinib

Experimental group

Description:

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.

Treatment:

Drug: Tucatinib

Drug: Trastuzumab Emtansine

Arm J: Trastuzumab Emtansine + Atezolizumab

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Trastuzumab Emtansine

Arm K: Ipatasertib + Atezolizumab

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Ipatasertib

Arm L: Ipatasertib + Atezolizumab

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: Ipatasertib

Arm M: Ipatasertib + Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Ipatasertib

Drug: Paclitaxel

Arm N: Atezolizumab + Tiragolumab

Experimental group

Description:

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

Treatment:

Drug: Atezolizumab

Drug: Tiragolumab

Arm O: Pralsetinib

Experimental group