KATE3: A Study of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo as a Treatment for Participants With Human Epidermal Growth Factor 2 (HER2)-Positive and Programmed Death-ligand 1 (PD-L1)-Positive Locally Advanced (LABC) or Metastatic Breast Cancer (MBC)

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04740918
• Collaborator: (none)
• Enrollment: 320
• Locations: 140
• Arms: 2
• Anticipated Duration (Months): 78.8
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy, safety and patient-reported outcomes of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo in participants with HER2-positive and PD-L1-positive LABC or MBC.Participants must have progressed either during or after prior trastuzumab- (+/- pertuzumab) and taxane-based therapy for LABC/MBC; or during (or within 6 months after completing) trastuzumab- (+/-pertuzumab) and taxane-based therapy in the neoadjuvant and/or adjuvant setting.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Trastuzumab Emtansine; Drug: Atezolizumab; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 320 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo in Patients With HER2-Positive and PD-L1-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab- (+/- Pertuzumab) and Taxane-Based Therapy (KATE3)
• Actual Study Start Date: Jun 7, 2021
• Anticipated Primary Completion Date: Aug 9, 2024
• Anticipated Study Completion Date: Dec 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A: Trastuzumab Emtansine and Placebo Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor.	Drug: Trastuzumab Emtansine; Trastuzumab emtansine 3.6 mg/kg IV infusion; Other Names: Kadcyla, T-DM1, RO5304020 ; Other: Placebo; Placebo matched to atezolizumab
Experimental: Arm B: Trastuzumab Emtansine and Atezolizumab Atezolizumab 1200 mg IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor.	Drug: Trastuzumab Emtansine; Trastuzumab emtansine 3.6 mg/kg IV infusion; Other Names: Kadcyla, T-DM1, RO5304020 ; Drug: Atezolizumab; Atezolizumab 1200 mg IV infusion; Other Names: Tecentriq, RO5541267, MPDL3280A

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) as Determined by Investigator's Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) [Baseline until disease progression, death or end of study (approximately 78 months)]

2. Overall Survival (OS) [From baseline until death or end of study (approximately 78 months)]

Secondary Outcome Measures

1. Percentage of Participants With Objective Response Rate (ORR) as Determined by Investigator's Assessment Using RECIST v1.1 [Baseline until disease progression, death or end of study (approximately 78 months)]

2. Duration of Objective Response (DOR) as Determined by Investigator Assessment Using RECIST v1.1 [Baseline until disease progression, death or end of study (approximately 78 months)]

3. PFS as Determined by a Blinded Independent Central Review Committee Using RECIST v1.1 [Baseline until disease progression, death or end of study (approximately 78 months)]

4. PFS in Participants with Baseline Brain Metastases as Determined by Investigator Assessment Using RECIST v1.1 [Baseline until disease progression, death or end of study (approximately 78 months)]

5. OS in Participants with Baseline Brain Metastases [From baseline until death or end of study (approximately 78 months)]

6. Central Nervous System (CNS) PFS as Determined by Investigator Assessment Using RECIST v1.1 in Participants with or Without Baseline CNS Metastases [Baseline until disease progression, death or end of study (approximately 78 months)]

7. Mean Absolute Scores in Function (Physical, Role) and Global Health Status (GHS)/Quality of Life (QoL) as Measured by the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30) [From Cycle 1 until 3 months after study completion]

8. Mean Change-From-Baseline Scores in Function (Physical, Role) and GHS/QoL as Measured by the EORTC QLQ-C30 [From Cycle 1 until 3 months after study completion]

9. Percentage of Participants with Clinically Meaningful Deterioration in GHS/QoL Physical, and Role Function as Measured by the EORTC QLQ-C30 [From Cycle 1 until 3 months after study completion]

10. Percentage of Participants with Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 [Baseline up to end of study (approximately 78 months)]

11. Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine [Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months)]

12. Cmax of Atezolizumab [Day 1 of Cycles 1, 2, 3, 4 and 8 and every 8 cycles thereafter (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months)]

13. Percentage of Participants With Anti-Drug Antibodies (ADAs) to Trastuzumab Emtansine [Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months)]

14. Percentage of Participants With ADAs to Atezolizumab [Day 1 of Cycles 1, 2, 3, 4 and 8 and every 8 cycles thereafter (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HER2+ and PD-L1+ locally advanced (LABC) or metastatic breast cancer (MBC)

• Progression must have occurred during most recent treatment for LABC/MBC or during, or within 6 months after completing, neoadjuvant and/or adjuvant therapy

• Prior treatment with trastuzumab (+/- pertuzumab) and taxane in the neoadjuvant and/or adjuvant, locally advanced, or metastatic setting

• No more than two prior lines of therapy in the metastatic setting

• Measurable disease per RESIST version 1.1

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Life expectancy >= 6 months

• Adequate hematologic and end-organ function

• For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs

• For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

• Prior treatment with trastuzumab emtansine in metastatic setting

• History of exposure to cumulative doses of anthracyclines

• Symptomatic or actively progressing central nervous system (CNS) metastases; asymptomatic CNS lesions ≤ 2cm without clinical requirement for local intervention or asymptomatic patients with treated CNS lesions are eligible

• Current Grade >= 3 peripheral neuropathy

• Cardiopulmonary dysfunction

• History of malignancy within 5 years prior to initiation of study treatment, with the exception of the cancer under investigation and malignancies with a negligible risk of metastasis or death

• History of leptomeningeal disease

• Active or history of autoimmune disease or immune deficiency

• Active hepatitis B, hepatitis C and/or tuberculosis

• Prior allogeneic stem cell or solid organ transplantation

• Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, during treatment, or within 5 months following the last dose of study treatment

• Pregnancy or lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Orange Coast Memorial Medical Center	Fountain Valley	California	United States	92708
2	Emad Ibrahim, Md, Inc	Redlands	California	United States	92373
3	Northwest Georgia Oncology Centers PC - Marietta	Marietta	Georgia	United States	30060
4	Mercy Health Research	Saint Louis	Missouri	United States	63141
5	San Juan Oncology Associates, PC	Farmington	New Mexico	United States	87401
6	Clinical Research Alliance	Westbury	New York	United States	11590
7	Magee Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
8	Lake Macquarie Private Hospital	Gateshead	New South Wales	Australia	2290
9	Royal North Shore Hospital; Oncology	St. Leonards	New South Wales	Australia	2065
10	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
11	Peter MacCallum Cancer Center	North Melbourne	Victoria	Australia	3051
12	Sunshine Hospital	St Albans	Victoria	Australia	3021
13	Hospital Sao Rafael - HSR	Salvador	BA	Brazil	41253-190
14	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO	Brazil	74605-070
15	Hospital do Cancer de Pernambuco - HCP	Recife	PE	Brazil	50040-000
16	Hospital de Caridade de Ijui; Oncologia	Ijui	RS	Brazil	98700-000
17	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS	Brazil	91350-200
18	Hospital de Base de Sao Jose do Rio Preto	Sao Jose do Rio Preto	SP	Brazil	15090-000
19	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda	Sao Paulo	SP	Brazil	01317-001
20	Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA	Sao Paulo	SP	Brazil	04014-002
21	Royal Victoria Hospital	Barrie	Ontario	Canada	L4M 6M2
22	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario	Canada	L1G 2B9
23	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario	Canada	K1H 8L6
24	Sunnybrook Research Institute	Toronto	Ontario	Canada	M4N 3M5
25	Centre Hospitalier de l'Université de Montréal (CHUM)	Montreal	Quebec	Canada	H2X 0C2
26	McGill University Health Center	Montreal	Quebec	Canada	H4A 3J1
27	Jewish General Hospital; Research Unit	Montréal	Quebec	Canada	H3T 1E2
28	CHUS (Centre Hospitalier Universitaire de Sherbrooke)	Sherbrooke	Quebec	Canada	J1H 5N4
29	Peking University People's Hospital	Beijing		China	100044
30	Beijing Cancer Hospital	Beijing		China	100142
31	The First Hospital of Jilin University	Changchun City		China	130021
32	Hunan Cancer Hospital	Changsha City		China	410013
33	Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Breast Tumor Center	Guangzhou City		China	510120
34	The Second Affiliated Hospital, Zhejiang University	Hangzhou		China	310009
35	Zhejiang Provincial People's Hospital; Oncology& Breast	Hangzhou		China	310014
36	Harbin Medical University Cancer Hospital	Harbin		China	150081
37	Yunnan Cancer Hospital; Breast Surgery	Kunming City		China	650100
38	Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)	Nanjing City		China	210029
39	Peking University Shenzhen Hospital	Shenzhen		China	518036
40	Tianjin Medical University Cancer Institute & Hospital	Tianjing		China	300060
41	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City		China	430023
42	Shanxi Provincial People's Hospital	Xian		China	710068
43	Zhejiang Cancer Hospital	Zhejiang		China	310022
44	Henan Cancer Hospital	Zhengzhou		China	450008
45	Clinica Vida	Medellin		Colombia
46	Oncomedica S.A.	Monteria		Colombia	230002
47	Oncólogos de Occidente	Pereira		Colombia	600004
48	Clinical Hospital Centre Split	Split		Croatia	21000
49	Clinical Hospital Center Sestre Milosrdnice; Clinic for tumors	Zagreb		Croatia	10000
50	Clinical Hospital Centre Zagreb	Zagreb		Croatia	10000
51	Helsinki University Central Hospital; Dept of Oncology	Helsinki		Finland	00250
52	Oulu University Hospital; Oncology	Oulu		Finland	90029
53	Tampere University Hospital; Dept of Oncology	Tampere		Finland	33520
54	CHU Amiens - Hopital Sud	Amiens		France	80054
55	Polyclinique Bordeaux Nord Aquitaine	Bordeaux		France	33300
56	Chu Grenoble - Hopital Albert Michallon; Departement de Cancero-Hematologie	Grenoble		France	38043
57	Centre Oscar Lambret; Senologie	Lille		France	59020
58	Centre Antoine Lacassagne, Centre de Lutte Contre le Cancer (CLCC) de Nice	Nice		France	06189
59	Groupe Hospitalier Diaconesses Croix Saint-Simon - Site Reuilly)	Paris		France	75020
60	Chu La Miletrie; Oncologie Medicale	Poitiers		France	86021
61	Institut Curie - Hopital Rene Huguenin	Saint-Cloud		France	92211
62	Institut Universitaire du Cancer de Toulouse-Oncopole	Toulouse		France	31059
63	Centre Alexis Vautrin; Oncologie Medicale	Vandoeuvre-les-nancy		France	54519
64	Onkozentrum Dres. Göhler	Dresden		Germany	01127
65	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg		Germany	69120
66	St. Elisabeth-Krankenhaus; Brustzentrum	Köln		Germany	50935
67	Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine	Athens		Greece	115 22
68	Alexandras General Hospital of Athens; Oncology Department	Athens		Greece	115 28
69	University General Hospital of Heraklion;Internal Medicine-Oncology Clinic	Heraklion, Crete		Greece	711 10
70	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki		Greece	546 45
71	Szent Margit Hospital	Budapest		Hungary	1032
72	Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly	Budapest		Hungary	1122
73	Debreceni Egyetem Klinikai Kozpont ; Department of Oncology	Debrecen		Hungary	4032
74	Borsod-Abauj-Zemplen Megyei Korhaz Es Egyetemi Oktato Korhaz; Onkologiai Osztaly	Miskolc		Hungary	3501
75	Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati	Avellino	Campania	Italy	83100
76	Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica	Napoli	Campania	Italy	80131
77	Università degli Studi Federico II; Clinica di Oncologia Medica	Napoli	Campania	Italy	80131
78	Azienda Ospedaliera S. Orsola-Malpighi	Bologna	Emilia-Romagna	Italy	40138
79	Azienda Unità Sanitaria Locale di Reggio Emilia/IRCCS	Reggio Emilia	Emilia-Romagna	Italy	42123
80	Ospedale Policlinico San Martino; Ist. di Ricovero e Cura a Carattere Scientifico per l'Oncologia	Genova	Liguria	Italy	16132
81	Asst Papa Giovanni XXIII	Bergamo	Lombardia	Italy	24100
82	Ospedale San Raffaele; Medical Oncology	Milano	Lombardia	Italy	20132
83	Istituto Europeo Di Oncologia	Milano	Lombardia	Italy	20141
84	Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia	Rozzano	Lombardia	Italy	20089
85	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana	Italy	56100
86	Seoul National University Hospital	Seoul		Korea, Republic of	03080
87	Asan Medical Center	Seoul		Korea, Republic of	05505
88	Korea University Guro Hospital	Seoul		Korea, Republic of	08308
89	Haukeland universitetssjukehus, Avd. for kreftbehandling og medisinsk fysikk	Bergen		Norway	5021
90	Sykehuset Østfold Kalnes; Onkologisk seksjon	Grålum		Norway	1714
91	Oslo Universitetssykehus HF; Ullevål sykehus	Oslo		Norway	0450
92	Stavanger Universitetssykehus, Helse Stavanger HF	Stavanger		Norway	4011
93	Cebu Doctors' University Hospital; Research Office	Cebu City		Philippines	6000
94	St. Luke's Medical Center; Human Cancer Biobank Research Center	Quezon City		Philippines	1102
95	Cardinal Santos Medical Center; Lower Ground Floor Research Room, Cancer Center	San Juan		Philippines	1502
96	Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii	Gdansk		Poland	80-219
97	Przychodnia Lekarska KOMED, Roman Karaszewski	Konin		Poland	62-500
98	Szpital Wojewódzki im. Mikołaja Kopernika; Oddział Dzienny Chemioterapii	Koszalin		Poland	75-581
99	Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii	Kraków		Poland	30-688
100	Centrum Terapii Wspolczesnej J.M.Jasnorzewska Spolka Komandytowo-Akcyjna	Lodz		Poland	90-242
101	Opolskie Centrum Onkologii;Oddzial Onkologii Klinicznej	Opole		Poland	45-060
102	Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna	Poznan		Poland	60-569
103	Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii	Warszawa		Poland	02-781
104	Mazowiecki Szpital Onkologiczny	Wieliszew		Poland	05-135
105	IPO de Lisboa; Servico de Oncologia Medica	Lisboa		Portugal	1099-023
106	Centro Clinico Champalimaud; Oncologia Medica	Lisboa		Portugal	1400-038
107	Hospital de Santa Maria; Servico de Oncologia Medica	Lisboa		Portugal	1649-035
108	Centro Hospitalar do Porto - Hospital de Santo António; Oncologia	Porto		Portugal	4099-001
109	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
110	FSBSI "N. N. Blokhin Russian Cancer Research Center"	Moscow		Russian Federation	115478
111	City Clinical Oncology Dispensary, SPb SBIH CCOD	Saint-Petersburg		Russian Federation	198255
112	Samara Regional Oncology Dispensary	Samara		Russian Federation	443031
113	State Healthcare Institution "Regional Clinical Oncology Dispensary"	Saratov		Russian Federation	410053
114	St. Petersburg Clinical Scientific Center of special services medical assis (oncology)	ST Petersburg		Russian Federation	197758
115	SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan	Ufa		Russian Federation	450054
116	Institute of Oncology Ljubljana	Ljubljana		Slovenia	1000
117	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon	Spain	12002
118	Hospital Universitario Quiron Madrid; Servicio de Oncologia	Pozuelo de Alarcón	Madrid	Spain	28223
119	Complexo Hospitalario de Vigo. Hospital Álvaro Cunqueiro; Servicio de Oncología	Vigo	Pontevedra	Spain	36312
120	Hospital Universitari Vall d'Hebron; Oncology	Barcelona		Spain	08035
121	Hospital Universitario La Paz; Servicio de Oncologia	Madrid		Spain	28046
122	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga		Spain	29010
123	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga		Spain	29011
124	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla		Spain	41013
125	Adana Baskent University Medical Faculty; Oncology	Adana		Turkey	01220
126	Sakarya Universitesi Egitim ve Arastirma Hastanesi	Adapazari/Sakarya		Turkey	54100
127	Memorial Ankara Hastanesi	Ankara		Turkey	06520
128	Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji	Bakirkoy / Istanbul		Turkey	34147
129	Acibadem University School of Medicine Altunizade Hospital Oncology Service	Istanbul		Turkey	34742
130	Katip Celebi University Ataturk Training and Research Hospital; Oncology	Izmir		Turkey	35360
131	Kayseri Acibadem Hospital	Kayseri		Turkey	38000
132	Inonu University Faculty of Medicine Turgut Ozal Medical Center; Onkoloji, Elazig Yolu,	Malatya		Turkey	44280
133	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara		Turkey	06230
134	Leicester Royal Infirmary NHS Trust	Leicester		United Kingdom	LE1 5WW
135	UCL Hospital NHS Trust	London		United Kingdom	NW1 2PG
136	Guys and St Thomas NHS Foundation Trust, Guys Hospital	London		United Kingdom	SE1 9RT
137	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
138	Milton Keynes University Hospital	Milton Keynes		United Kingdom	MK6 5LD
139	Nottingham University Hospitals City Campus; Nottingham Cancer Clinical Trials Team	Nottingham		United Kingdom	NG5 1PB
140	Peterborough City Hospital	Peterborough		United Kingdom	PE3 9GZ

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04740918
• Other Study ID Numbers: MO42319; 2020-002818-41
• First Posted: Feb 5, 2021
• Last Update Posted: Aug 18, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab; Ado-Trastuzumab Emtansine; Atezolizumab; Maytansine

Study Results

No Results Posted as of Aug 18, 2022