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

Sponsor

Genentech, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04632992

Collaborator

(none)

260

Enrollment

Locations

Arms

47.6

Anticipated Duration (Months)

5.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Unresectable or Metastatic Solid Malignancy	Drug: Entrectinib Drug: Inavolisib Drug: Alectinib Drug: Ipatasertib Drug: Atezolizumab Drug: Trastuzumab Emtansine Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf Drug: Tucatinib Drug: Investigator's Choice of Chemotherapy Drug: Paclitaxel Drug: Tiragolumab Drug: Pralsetinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

MyTACTIC: An Open-Label Phase II Study Evaluating Targeted Therapies in Patients Who Have Advanced Solid Tumors With Genomic Alterations or Protein Expression Patterns Predictive of Response

Actual Study Start Date :

Jan 13, 2021

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Entrectinib Participants in this treatment arm must have a positive tumor biomarker result for ROS1 gene fusion.	Drug: Entrectinib 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. Other Names: Rozlytrek™ RG6268 RO7102122
Experimental: Arm B: Inavolisib Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.	Drug: Inavolisib 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. Other Names: GDC-0077 RG6114 RO7113755
Experimental: Arm C: Alectinib Participants in this treatment arm must have a positive tumor biomarker result for ALK rearrangement tumors.	Drug: Alectinib 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. Other Names: Alecensa® RG7853 RO5424802
Experimental: Arm D: 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.	Drug: Ipatasertib 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. Other Names: GDC-0068 RG7440 RO5532961
Experimental: Arm E: Atezolizumab + 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).	Drug: Atezolizumab 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). Other Names: Tecentriq® RG7446 RO5541267 Drug: Investigator's Choice of Chemotherapy 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.
Experimental: Arm F: Trastuzumab Emtansine + Atezolizumab Participants in this treatment arm must have a positive tumor biomarker result for ERBB2 mutations or amplification without known TMB high or MSI high/dMMR.	Drug: Atezolizumab 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). Other Names: Tecentriq® RG7446 RO5541267 Drug: Trastuzumab Emtansine 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. Other Names: Kadcyla® RG3502 RO5304020
Experimental: Arm G: PH FDC SC Participants in this treatment arm must have a positive tumor biomarker result for ERBB2 mutation or amplification without known TMB high or MSI high/dMMR.	Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf 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. Other Names: PHESGO™ PH FDC SC Fixed dose combination of trastuzumab and pertuzumab administered subcutaneously RG6264 RO7198574
Experimental: Arm H: PH FDC SC + Investigator's Choice of Chemotherapy Participants in this treatment arm must have a positive tumor biomarker result for ERBB2 mutation or amplification without known TMB high or MSI high/dMMR.	Drug: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf 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. Other Names: PHESGO™ PH FDC SC Fixed dose combination of trastuzumab and pertuzumab administered subcutaneously RG6264 RO7198574 Drug: Investigator's Choice of Chemotherapy 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.
Experimental: Arm I: Trastuzumab Emtansine + Tucatinib Participants in this treatment arm must have a positive tumor biomarker result for ERBB2 mutation or amplification without known TMB high or MSI high/dMMR.	Drug: Trastuzumab Emtansine 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. Other Names: Kadcyla® RG3502 RO5304020 Drug: Tucatinib Tucatinib 300 mg will be administered orally BID continuously starting from Cycle 1 Day 1 onwards. Other Names: Tukysa™
Experimental: Arm J: Trastuzumab Emtansine + Atezolizumab Participants in this treatment arm must have positive tumor biomarker results for ERBB2 mutation or amplification and TMB high or MSI high/dMMR.	Drug: Atezolizumab 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). Other Names: Tecentriq® RG7446 RO5541267 Drug: Trastuzumab Emtansine 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. Other Names: Kadcyla® RG3502 RO5304020
Experimental: Arm K: Ipatasertib + Atezolizumab Participants in this treatment arm must have a positive tumor biomarker result for PI3KCA activating mutation.	Drug: Ipatasertib 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. Other Names: GDC-0068 RG7440 RO5532961 Drug: Atezolizumab 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). Other Names: Tecentriq® RG7446 RO5541267
Experimental: Arm L: Ipatasertib + 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.	Drug: Ipatasertib 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. Other Names: GDC-0068 RG7440 RO5532961 Drug: Atezolizumab 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). Other Names: Tecentriq® RG7446 RO5541267
Experimental: Arm M: Ipatasertib + 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.	Drug: Ipatasertib 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. Other Names: GDC-0068 RG7440 RO5532961 Drug: Paclitaxel 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.
Experimental: Arm N: Atezolizumab + Tiragolumab Participants in this treatment arm must have a positive tumor biomarker result for either TMB high or MSI high/dMMR.	Drug: Atezolizumab 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). Other Names: Tecentriq® RG7446 RO5541267 Drug: Tiragolumab 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. Other Names: RG6058 RO7092284 MTIG7192A
Experimental: Arm O: Pralsetinib Participants in this treatment arm must have a positive tumor biomarker result for RET fusion.	Drug: Pralsetinib 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. Other Names: GAVRETO™ RG6396 RO7499790

Outcome Measures

Primary Outcome Measures

Percentage of Participants with Confirmed Overall Response, as Assessed by the Investigator According to RECIST v1.1 or According to RANO Criteria for Primary CNS Tumors [Up to 4 years]
RANO = Response Assessment in Neuro-Oncology; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors, Version 1.1

Secondary Outcome Measures

Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria [Up to 4 years]
Duration of Response, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria [Up to 4 years]
Overall Survival [Up to 4 years]
Progression-Free Survival Rate at Every 3 Months, Defined as the Percentage of Participants who are Progression-Free as Determined by the Investigator According to RECIST v1.1 or RANO Criteria [At every 3 months until study completion (up to 4 years)]
Overall Survival Rate at Every 3 Months, Defined as the Percentage of Participants who are Alive [At every 3 months until study completion (up to 4 years)]
Percentage of Participants with Disease Control, as Determined by the Investigator According to RECIST v1.1 or RANO Criteria [Up to 4 years]
Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) [From Baseline until 28 days after the final dose of study drug (up to 4 years)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham: The Kirklin Clinic	Birmingham	Alabama	United States	35233
2	Alaska Oncology and Hematology	Anchorage	Alaska	United States	99508
3	Arizona Clinical Research Ctr	Oro Valley	Arizona	United States	85755-6216
4	Genesis Cancer Center	Hot Springs	Arkansas	United States	71913
5	California Cancer Associates for Research and Excellence - Encinitas	Encinitas	California	United States	92024-1328
6	Los Angeles Hematology Oncology Medical Group	Los Angeles	California	United States	90017
7	Pacific Cancer Care - Monterey	Monterey	California	United States	93940
8	Kaiser Permanente Med Center	Oakland	California	United States	94611
9	Kaiser Permanente Medical Center - Roseville	Roseville	California	United States	95661
10	Kaiser Permanente - Sacramento Medical Center and Medical Offices	Sacramento	California	United States	95825
11	Kaiser Permanente - San Francisco Medical Center	San Francisco	California	United States	94118
12	Kaiser Permanente - San Jose Medical Center	San Jose	California	United States	95119
13	Kaiser Permanente - San Leandro Medical Center	San Leandro	California	United States	94577
14	California Cancer Associates for Research & Excellence, Inc.	San Marcos	California	United States	92069
15	Kaiser Permanente - Santa Clara	Santa Clara	California	United States	95051
16	Sarcoma Oncology Center	Santa Monica	California	United States	90403
17	Kaiser Permanente - South San Francisco	South San Francisco	California	United States	94080
18	Kaiser Permanente Medical Ctr	Vallejo	California	United States	94589
19	Ventura County Hematology Oncology Specialists	Ventura	California	United States	93003
20	K. Permanente - Walnut Creek	Walnut Creek	California	United States	94596
21	Eastern CT Hematology and Oncology Associates	Norwich	Connecticut	United States	06360-2740
22	SCRI Florida Cancer Specialists South	Fort Myers	Florida	United States	33916
23	Florida Cancer Specialists - NORTH - SCRI - PPDS	Saint Petersburg	Florida	United States	33705-1400
24	Florida Cancer Specialists - PAN - SCRI - PPDS	Tallahassee	Florida	United States	32308
25	Florida Cancer Specialists - EAST - SCRI - PPDS	West Palm Beach	Florida	United States	33401-3406
26	St Luke's Cancer Institute	Boise	Idaho	United States	83712
27	Hematology and Oncology Clinic	Baton Rouge	Louisiana	United States	70809
28	Mercy Medical Center	Baltimore	Maryland	United States	21202
29	Saint Agnes Hospital - Baltimore - Hunt - PPDS	Baltimore	Maryland	United States	21229-5201
30	Ascension St. John Hospital	Detroit	Michigan	United States	48236
31	St Louis Cancer Care LLP	Bridgeton	Missouri	United States	63044
32	Frontier Cancer Center and Blood Institute	Billings	Montana	United States	59102
33	Southeast Nebraska Cancer Center	Lincoln	Nebraska	United States	68510-2496
34	New Jersey Hematology Oncology Associates LLC	Brick	New Jersey	United States	08724-3009
35	Astera Cancer Care East Brunswick	East Brunswick	New Jersey	United States	08816
36	Eastchester Center for Cancer Care	Bronx	New York	United States	10469
37	Central Park Hematology and Oncology	New York	New York	United States	10028-0506
38	New York Cancer & Blood Specialists	Port Jefferson Station	New York	United States	11776
39	Messino Cancer Centers	Asheville	North Carolina	United States	28806
40	Gabrail Cancer Center	Canton	Ohio	United States	44718
41	Tri County Hematologyoncology	Canton	Ohio	United States	44718
42	Mark H. Zangmeister Center	Columbus	Ohio	United States	43219
43	Toledo Clinic Cancer Center	Toledo	Ohio	United States	43623-3536
44	Kaiser Permanente Center For Health Research	Portland	Oregon	United States	97227-1196
45	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee	United States	37404
46	The West Clinic, PC dba West Cancer Center	Memphis	Tennessee	United States	38138
47	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
48	The Center for Cancer and Blood Disorders - PPDS	Fort Worth	Texas	United States	76104-4611
49	Mays Cancer Center at UT Health San Antonio MD Anderson Cancer	San Antonio	Texas	United States	78229
50	Virginia Commonwealth University - Massey Cancer Center	Richmond	Virginia	United States	23298
51	Northwest Medical Specialties B	Federal Way	Washington	United States	98003