A Study Evaluating Targeted Therapies in Participants Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response
- Conditions
- Advanced Unresectable or Metastatic Solid Malignancy
- Interventions
- Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxfDrug: Investigator's Choice of Chemotherapy
- Registration Number
- NCT04632992
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 252
- 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)
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Entrectinib Entrectinib Participants in this treatment arm must have a positive tumor biomarker result for ROS1 gene fusion. Arm B: Inavolisib Inavolisib Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation. Arm C: Alectinib Alectinib Participants in this treatment arm must have a positive tumor biomarker result for ALK rearrangement tumors. Arm D: Ipatasertib Ipatasertib 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. Arm E: Atezolizumab + Investigator's Choice of Chemotherapy Atezolizumab 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). Arm E: Atezolizumab + Investigator's Choice of Chemotherapy Investigator's Choice of Chemotherapy 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). Arm F: Trastuzumab Emtansine + Atezolizumab Atezolizumab 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. Arm F: Trastuzumab Emtansine + Atezolizumab Trastuzumab Emtansine 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. Arm G: PH FDC SC Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf 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. Arm H: PH FDC SC + Investigator's Choice of Chemotherapy Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf 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. Arm H: PH FDC SC + Investigator's Choice of Chemotherapy Investigator's Choice of Chemotherapy 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. Arm I: Trastuzumab Emtansine + Tucatinib Trastuzumab Emtansine 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. Arm I: Trastuzumab Emtansine + Tucatinib Tucatinib 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. Arm J: Trastuzumab Emtansine + Atezolizumab Atezolizumab Participants in this treatment arm must have positive tumor biomarker results for HER2 mutation or amplification and TMB high or MSI high/dMMR. Arm J: Trastuzumab Emtansine + Atezolizumab Trastuzumab Emtansine Participants in this treatment arm must have positive tumor biomarker results for HER2 mutation or amplification and TMB high or MSI high/dMMR. Arm K: Ipatasertib + Atezolizumab Ipatasertib Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation. Arm K: Ipatasertib + Atezolizumab Atezolizumab Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation. Arm L: Ipatasertib + Atezolizumab Ipatasertib 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. Arm L: Ipatasertib + Atezolizumab Atezolizumab 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. Arm M: Ipatasertib + Paclitaxel Ipatasertib 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. Arm M: Ipatasertib + Paclitaxel Paclitaxel 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. Arm N: Atezolizumab + Tiragolumab Atezolizumab Participants in this treatment arm must have a positive tumor biomarker result for either TMB high or MSI high/dMMR. Arm N: Atezolizumab + Tiragolumab Tiragolumab Participants in this treatment arm must have a positive tumor biomarker result for either TMB high or MSI high/dMMR. Arm O: Pralsetinib Pralsetinib Participants in this treatment arm must have a positive tumor biomarker result for RET fusion.
- Primary Outcome Measures
Name Time Method 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 Up to 32 months 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.
- Secondary Outcome Measures
Name Time Method 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) PFS=time from start of treatment to the first occurrence of disease progression (PD) or death from any cause, whichever occurs first, per RECIST v1.1, or RANO. Per RECIST, PD=≥20% increase in sum of diameters of lesions, using the smallest sum during the study as reference, including baseline (BL). Per RANO, PD= ≥25% increase in sum of products of perpendicular diameters of enhancing lesions compared to smallest tumor measurement at BL/best response, on stable/increasing corticosteroids (CS) dose; Significant/ ≥25% increase of T2/FLAIR non-enhancing lesion on stable/increasing CS dose compared to BL/best response after therapy start; Presence of new lesions/increase of enhancement; Clear progression of non-measurable disease; Definite clinical deterioration only due to tumor/decrease in CS dose; Failure to return for evaluation due to death/deterioration. Kaplan-Meier methodology was used to estimate PFS; patients without an event were censored on the last available assessment day.
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) DOR was defined as the time from the date of the first confirmed complete response (CR) or partial response (PR) to disease progression (PD) or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 or RANO. CR \& PR were defined per RECIST or RANO as outlined in the description for the cORR outcome measure (OM). PD was defined per RECIST or RANO as outlined in the description for the PFS OM. Kaplan-Meier methodology was used to estimate the median DOR. The 95% confidence intervals for the median DOR were computed by the method of Brookmeyer and Crowley. Participants who did not experience death or PD were censored on the day of the last available assessment.
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 The PFS rates were calculated using the Kaplan-Meier (KM) method to estimate the percent survival probability of participants (i.e., PFS event-free: did not experience PD or death from any cause) in each treatment arm at landmark timepoints. The 95% confidence intervals for each PFS rate were computed by the method of Greenwood. PFS was defined as the time from the start of study treatment to the first occurrence of PD or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 or RANO. PD was defined per RECIST or RANO as outlined in the description for the PFS OM. Participants who did not experience death or PD were censored on the day of the last available assessment. The number analyzed per landmark timepoint actually represents the number of participants who remained at risk of experiencing a PFS event at that timepoint. Percentages are rounded off to the nearest decimal point.
Percentage of Participants With Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria Up to 32 months Disease control rate was defined as the percentage of participants whose best response was confirmed CR, confirmed PR, or a response of CR, PR, stable disease (SD), or non-CR/non-PD for a minimum of 98 days for 28-day cycle arms or 70 days for 21-day cycle arms after the first treatment date. CR \& PR were defined per RECIST/RANO as outlined in the description for the cORR OM. SD per RECIST: Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. SD per RANO: Participant does not qualify for CR, PR, or minor response or PD; Stable non-enhancing (T2/FLAIR) lesions or abnormalities on same or lower dose of corticosteroids compared to baseline; No new lesions or new T2 or FLAIR abnormalities apart from those consistent with radiation effect, \& no new or increased enhancement; Participants on a should be corticosteroid dose that is not greater than dose at baseline scan \& is stable or improved clinically; Clinical status, stable/improved.
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) An AE is an untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with the product. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to it. AEs were graded for severity according to NCI CTCAE v5.0. Grade 1= Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3 = Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4= Life-threatening consequences/urgent intervention indicated; Grade 5= Death related to adverse event.
Trial Locations
- Locations (38)
Sarah Cannon Research Institute / Tennessee Oncology
🇺🇸Chattanooga, Tennessee, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Alaska Oncology and Hematology
🇺🇸Anchorage, Alaska, United States
Arizona Clinical Research Ctr
🇺🇸Oro Valley, Arizona, United States
Genesis Cancer Center
🇺🇸Hot Springs, Arkansas, United States
California Cancer Associates for Research and Excellence - Encinitas
🇺🇸Encinitas, California, United States
Los Angeles Hematology Oncology Medical Group
🇺🇸Los Angeles, California, United States
Pacific Cancer Care - Monterey
🇺🇸Monterey, California, United States
Kaiser Permanente - San Francisco Medical Center
🇺🇸San Francisco, California, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
Kaiser Permanente Medical Ctr
🇺🇸Vallejo, California, United States
Ventura County Hematology Oncology Specialists
🇺🇸Ventura, California, United States
Eastern CT Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
SCRI Florida Cancer Specialists South
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists - NORTH - SCRI - PPDS
🇺🇸Saint Petersburg, Florida, United States
Florida Cancer Specialists - PAN - SCRI - PPDS
🇺🇸Tallahassee, Florida, United States
Florida Cancer Specialists - EAST - SCRI - PPDS
🇺🇸West Palm Beach, Florida, United States
St Luke?s Cancer Institute
🇺🇸Boise, Idaho, United States
Hematology and Oncology Clinic
🇺🇸Baton Rouge, Louisiana, United States
Saint Agnes Hospital - Baltimore - Hunt - PPDS
🇺🇸Baltimore, Maryland, United States
Ascension St. John Hospital
🇺🇸Detroit, Michigan, United States
Frontier Cancer Center and Blood Institute
🇺🇸Billings, Montana, United States
Southeast Nebraska Cancer Center
🇺🇸Lincoln, Nebraska, United States
New Jersey Hematology Oncology Associates LLC
🇺🇸Brick, New Jersey, United States
Astera Cancer Care East Brunswick
🇺🇸East Brunswick, New Jersey, United States
Eastchester Center for Cancer Care
🇺🇸Bronx, New York, United States
New York Cancer & Blood Specialists
🇺🇸Bronx, New York, United States
Central Park Hematology and Oncology
🇺🇸New York, New York, United States
Messino Cancer Centers
🇺🇸Asheville, North Carolina, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Tri County Hematologyoncology
🇺🇸Canton, Ohio, United States
SCRI Mark H. Zangmeister Center
🇺🇸Columbus, Ohio, United States
Kaiser Permanente Center For Health Research
🇺🇸Portland, Oregon, United States
The West Clinic, PC dba West Cancer Center
🇺🇸Memphis, Tennessee, United States
The Center for Cancer and Blood Disorders - PPDS
🇺🇸Fort Worth, Texas, United States
Mays Cancer Center at UT Health San Antonio MD Anderson Cancer
🇺🇸San Antonio, Texas, United States
Virginia Commonwealth University - Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Northwest Medical Specialties B
🇺🇸Federal Way, Washington, United States