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

Genentech, Inc.252 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

252

Conditions

Advanced Unresectable or Metastatic Solid Malignancy

Interventions

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.

InavolisibDRUG

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.

AlectinibDRUG

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.

IpatasertibDRUG

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.

AtezolizumabDRUG

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).

Trastuzumab EmtansineDRUG

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.

Pertuzumab, Trastuzumab, and Hyaluronidase-zzxfDRUG

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.

TucatinibDRUG

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

Investigator's Choice of ChemotherapyDRUG

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.

PaclitaxelDRUG

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.

TiragolumabDRUG

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.

PralsetinibDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (38)

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

Outcomes

Primary Outcomes

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.

Time frame: Up to 32 months

Secondary Outcomes

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

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.

Time frame: 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

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.

Time frame: 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

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.

Time frame: 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

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.

Time frame: 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)

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.

Time frame: 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)

Data from ClinicalTrials.gov

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