Clinical trial NCT06926868: A Study of Izalontamab Brengitecan Versus Chemotherapy in Participants With Previously Untreated, Locally Advanced, Recurrent Inoperable, or Metastatic Triple-negative Breast Cancer Ineligible for Anti-PD(L)1 Drugs (IZABRIGHT-Breast01)
Official title: A Randomized, Open-label, Inferentially Seamless Phase 2/3 Study of Izalontamab Brengitecan (BMS-986507) Versus Treatment of Physician's Choice in Patients With Previously Untreated, Locally Advanced, Recurrent Inoperable,or Metastatic Triple-negative Breast Cancer (TNBC)or ER-low, HER2-negative BC Who Are Ineligible for Anti-PD1/PD-L1 Treatment
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Breast Neoplasms
Keywords: triple-negative breast cancer
antibody-drug conjugate
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: SystImmune Inc.
First posted: 2025-04-15
Enrollment: 560
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of iza-bren, a bi-specific antibody-drug conjugate against EGFR and HER3 with a topoisomerase inhibitor payload versus treatment of physician's choice (TPC) (paclitaxel, nab-paclitaxel, carboplatin plus gemcitabine, and capecitabine) for the treatment of first-line metastatic triple-negative breast cancer (TNBC) or estrogen receptor (ER)-low, human epidermal growth factor receptor 2 (HER2)-negative BC patients who are not candidates for anti-PD(L)1 therapy and endocrine therapies.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed and documented locally-advanced, recurrent inoperable, or metastatic TNBC (ER \< 1%, PgR \< 1%, HER2 IHC 0, 1+, or 2+ with FISH negative for HER2 gene amplification) or ER-low, HER2-negative BC (ER and / or PgR 1% to 10%, HER2 IHC 0, 1+, or 2+ with FISH negative for HER2 gene amplification) per ASCO/CAP criteria, based on the most recently analyzed biopsy or other pathology specimen.
* Patients with recurrent disease must have experienced disease relapse at least 6 months after finishing their last therapy with curative intent.
* Patients with TNBC must be considered ineligible for 1L chemotherapy combination treatment with an anti-PD-1 or an anti-PD-L1 due to either one of the following criteria:.
* Investigator-determined ineligibility based on PD-L1 negative disease determined and documented prior to trial screening as part of SoC.
* Has experienced disease relapse between 6 to 12 months after the completion of (neo)adjuvant therapy with an anti-PD(L)1.
* Has a severe auto-immune disease or other contraindication.
* Patients with ER-low, HER2-negative BC must be ineligible, in the opinion of the Investigator, for endocrine therapy-based treatments.
* No previous systemic therapy in the locally advanced, recurrent inoperable or metastatic setting (ie incurable setting).
* Measurable disease by CT or MRI as per RECIST v1.1.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Approximately 31 months from first participant randomization
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Approximately up to 57 months from first participant randomization
measure: Recommended Phase 3 Dose (RP3D) of BMS-986507
timeFrame: Approximately 19 months from first participant randomization
measure: Number of participants with treatment-related Adverse Events (AEs)
timeFrame: Approximately up to 57 months from first participant randomization
measure: Number of participants with laboratory abnormalities
timeFrame: Approximately up to 57 months from first participant randomization
measure: Number of participants with serious AEs (SAEs)
timeFrame: Approximately up to 57 months from first participant randomization
measure: Number of participants with AEs leading to treatment discontinuation, interruption, dose reduction or dose delay
timeFrame: Approximately up to 57 months from first participant randomization
measure: Number of deaths
timeFrame: Approximately up to 57 months from first participant randomization
measure: Objective Response (OR)
timeFrame: Approximately 31 months from first participant randomization
measure: PFS rate
timeFrame: Approximately 31 months from first participant randomization
measure: PFS
timeFrame: Approximately 31 months from first participant randomization
measure: Disease control rate (DCR)
timeFrame: Approximately 31 months from first participant randomization
measure: Duration of Response (DOR)
timeFrame: Approximately 31 months from first participant randomization
measure: Time to Response (TTR)
timeFrame: Approximately 31 months from first participant randomization
measure: Time to subsequent treatment (TTST)
timeFrame: Approximately up to 57 months from first participant randomization
measure: Progression-free survival after next line of treatment (PFS2)
timeFrame: Approximately up to 57 months from first participant randomization
measure: Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
timeFrame: Approximately up to 57 months from first participant randomization
measure: Change from baseline in EORTC Breast Cancer-specific Quality of Life Questionnaire (QLQ-BR23)
timeFrame: Approximately up to 57 months from first participant randomization
measure: Functional Assessment of Chronic Illness Therapy item GP5 (FACIT GP5) score
timeFrame: Approximately up to 57 months from first participant randomization
measure: Change from baseline in European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L)
timeFrame: Approximately up to 57 months from first participant randomization
Other outcomes:
Locations:
city: Hot Springs
country: United States
facility: Local Institution - 0303
state: Arkansas
city: Cerritos
country: United States
facility: Local Institution - 0307
state: California
city: Cerritos
country: United States
facility: Local Institution - 0308
state: California
city: Cerritos
country: United States
facility: Local Institution - 0309
state: California
city: Long Beach
country: United States
facility: Local Institution - 0311
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0290
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0283
state: California
city: Whittier
country: United States
facility: Local Institution - 0328
state: California
city: Aurora
country: United States
facility: Local Institution - 0289
state: Colorado
city: Newark
country: United States
facility: Local Institution - 0304
state: Delaware
city: Miami
country: United States
facility: Local Institution - 0282
state: Florida
city: Pembroke Pines
country: United States
facility: Local Institution - 0296
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0294
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0278
state: Illinois
city: Chicago
country: United States
facility: Local Institution - 0280
state: Illinois
city: Decatur
country: United States
facility: Local Institution - 0275
state: Illinois
city: O'Fallon
country: United States
facility: Local Institution - 0324
state: Illinois
city: Covington
country: United States
facility: Local Institution - 0286
state: Louisiana
city: Boston
country: United States
facility: Local Institution - 0288
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0287
state: Massachusetts
city: Minneapolis
country: United States
facility: Local Institution - 0313
state: Minnesota
city: Kansas City
country: United States
facility: Local Institution - 0284
state: Missouri
city: New York
country: United States
facility: Local Institution - 0312
state: New York
city: New York
country: United States
facility: Local Institution - 0279
state: New York
city: Westbury
country: United States
facility: Local Institution - 0295
state: New York
city: White Plains
country: United States
facility: Local Institution - 0285
state: New York
city: Durham
country: United States
facility: Local Institution - 0276
state: North Carolina
city: Eugene
country: United States
facility: Local Institution - 0316
state: Oregon
city: Philadelphia
country: United States
facility: Local Institution - 0310
state: Pennsylvania
city: Greenville
country: United States
facility: Local Institution - 0281
state: South Carolina
city: Austin
country: United States
facility: Local Institution - 0315
state: Texas
city: Houston
country: United States
facility: Local Institution - 0314
state: Texas
city: Tyler
country: United States
facility: Local Institution - 0305
state: Texas
city: Midlothian
country: United States
facility: Local Institution - 0277
state: Virginia
city: Roanoke
country: United States
facility: Local Institution - 0301
state: Virginia
city: Winchester
country: United States
facility: Local Institution - 0302
state: Virginia
city: Ciudad autónoma de Buenos Aires
country: Argentina
facility: Local Institution - 0011
state: Buenos Aires
city: ABB
country: Argentina
facility: Local Institution - 0214
state: Ciudad Autónoma De Buenos Aires
city: Río Cuarto
country: Argentina
facility: Local Institution - 0137
state: Córdoba
city: Rosario
country: Argentina
facility: Local Institution - 0142
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Local Institution - 0317
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Local Institution - 0012
city: Cordoba
country: Argentina
facility: Local Institution - 0143
city: Brisbane
country: Australia
facility: Local Institution - 0035
state: Queensland
city: Ballarat Central
country: Australia
facility: Local Institution - 0197
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution - 0031
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution - 0274
state: Victoria
city: Subiaco
country: Australia
facility: Local Institution - 0028
state: Western Australia
city: Graz
country: Austria
facility: Local Institution - 0292
state: Steiermark
city: Innsbruck
country: Austria
facility: Local Institution - 0268
state: Tirol
city: Salzburg
country: Austria
facility: Local Institution - 0267
city: St. Polten
country: Austria
facility: Local Institution - 0270
city: Wien
country: Austria
facility: Local Institution - 0269
city: Manaus
country: Brazil
facility: Local Institution - 0187
state: Amazonas
city: Fortaleza
country: Brazil
facility: Local Institution - 0147
state: Ceará
city: Vitória
country: Brazil
facility: Local Institution - 0157
state: Espírito Santo
city: Porto Alegre
country: Brazil
facility: Local Institution - 0199
state: Rio Grande Do Sul
city: São José do Rio Preto
country: Brazil
facility: Local Institution - 0164
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0153
city: São Paulo
country: Brazil
facility: Local Institution - 0144
city: São Paulo
country: Brazil
facility: Local Institution - 0149
city: Kelowna
country: Canada
facility: Local Institution - 0218
state: British Columbia
city: Victoria
country: Canada
facility: Local Institution - 0217
state: British Columbia
city: Ottawa
country: Canada
facility: Local Institution - 0265
state: Ontario
city: Montréal
country: Canada
facility: Local Institution - 0215
state: Quebec
city: Montréal
country: Canada
facility: Local Institution - 0219
state: Quebec
city: Sherbrooke
country: Canada
facility: Local Institution - 0216
state: Quebec
city: Medellín
country: Colombia
facility: Local Institution - 0195
state: Antioquia
city: Rionegro
country: Colombia
facility: Local Institution - 0201
state: Antioquia
city: Barranquilla
country: Colombia
facility: Local Institution - 0194
state: Atlántico
city: Puerto Colombia
country: Colombia
facility: Local Institution - 0182
state: Atlántico
city: Montería
country: Colombia
facility: Local Institution - 0181
state: COR
city: Bogota
country: Colombia
facility: Local Institution - 0327
state: Cundinamarca
city: Cali
country: Colombia
facility: Local Institution - 0183
state: Valle Del Cauca
city: Bordeaux
country: France
facility: Local Institution - 0089
state: Aquitaine
city: Dijon
country: France
facility: Local Institution - 0272
state: Côte-d'Or
city: Toulouse
country: France
facility: Local Institution - 0098
state: Haute-Garonne
city: Montpellier
country: France
facility: Local Institution - 0095
state: Hérault
city: Rennes
country: France
facility: Local Institution - 0099
state: Ille-et-Vilaine
city: Saint Herblain
country: France
facility: Local Institution - 0092
state: Loire-Atlantique
city: Reims
country: France
facility: Local Institution - 0091
state: Marne
city: Villejuif
country: France
facility: Local Institution - 0097
state: Paris
city: Marseille
country: France
facility: Local Institution - 0093
state: Provence-Alpes-Côte-d'Azur
city: Clermont-Ferrand
country: France
facility: Local Institution - 0096
state: Puy-de-Dôme
city: Lyon
country: France
facility: Local Institution - 0090
state: Rhône-Alpes
city: Lille
country: France
facility: Local Institution - 0094
city: Paris
country: France
facility: Local Institution - 0088
city: Esslingen
country: Germany
facility: Local Institution - 0320
state: Baden-Württemberg
city: Augsburg
country: Germany
facility: Local Institution - 0256
state: Bayern
city: München
country: Germany
facility: Local Institution - 0271
state: Bayern
city: Frankfurt
country: Germany
facility: Local Institution - 0306
state: Hessen
city: Düsseldorf
country: Germany
facility: Local Institution - 0293
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Local Institution - 0263
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Local Institution - 0254
state: Sachsen
city: Lübeck
country: Germany
facility: Local Institution - 0255
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Local Institution - 0261
city: Berlin
country: Germany
facility: Local Institution - 0260
city: Bonn
country: Germany
facility: Local Institution - 0259
city: Dresden
country: Germany
facility: Local Institution - 0258
city: Hannover
country: Germany
facility: Local Institution - 0257
city: Heidelberg
country: Germany
facility: Local Institution - 0262
city: Ulm
country: Germany
facility: Local Institution - 0291
city: Athens
country: Greece
facility: Local Institution - 0042
state: Attikí
city: Athens
country: Greece
facility: Local Institution - 0038
state: Attikí
city: Heraklion
country: Greece
facility: Local Institution - 0086
state: Irakleío
city: New Delhi
country: India
facility: Local Institution - 0266
state: Delhi
city: New Delhi
country: India
facility: Local Institution - 0206
state: Delhi
city: Mumbai
country: India
facility: Local Institution - 0131
state: Maharashtra
city: Nagpur
country: India
facility: Local Institution - 0134
state: Maharashtra
city: Chennai
country: India
facility: Local Institution - 0125
state: Tamil Nadu
city: Hyderabad
country: India
facility: Local Institution - 0130
state: Telangana
city: Varanasi
country: India
facility: Local Institution - 0133
state: Uttar Pradesh
city: Petah Tikva
country: Israel
facility: Local Institution - 0186
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: Local Institution - 0044
state: HaMerkaz
city: Hadera
country: Israel
facility: Local Institution - 0048
state: HaTsafon
city: Haifa
country: Israel
facility: Local Institution - 0123
state: HaTsafon
city: Jerusalem
country: Israel
facility: Local Institution - 0047
state: Yerushalayim
city: Napoli
country: Italy
facility: Local Institution - 0051
state: Campania
city: Bologna
country: Italy
facility: Local Institution - 0049
state: Emilia-Romagna
city: Aviano
country: Italy
facility: Local Institution - 0057
state: Friuli-Venezia Giulia
city: Genova
country: Italy
facility: Local Institution - 0054
state: Liguria
city: Pontedera
country: Italy
facility: Local Institution - 0053
state: Pisa
city: Prato
country: Italy
facility: Local Institution - 0055
state: Toscana
city: Milano
country: Italy
facility: Local Institution - 0052
city: Napoli
country: Italy
facility: Local Institution - 0058
city: Novara
country: Italy
facility: Local Institution - 0061
city: Padova
country: Italy
facility: Local Institution - 0056
city: Roma
country: Italy
facility: Local Institution - 0062
city: Nagoya
country: Japan
facility: Local Institution - 0236
state: Aichi
city: Chiba-shi
country: Japan
facility: Local Institution - 0230
state: Chiba
city: Matsuyama
country: Japan
facility: Local Institution - 0240
state: Ehime
city: Otashi
country: Japan
facility: Local Institution - 0226
state: Gunma
city: Sapporo
country: Japan
facility: Local Institution - 0222
state: Hokkaido
city: Kanazawa
country: Japan
facility: Local Institution - 0232
state: Ishikawa
city: Isehara
country: Japan
facility: Local Institution - 0234
state: Kanagawa
city: Yokohama
country: Japan
facility: Local Institution - 0237
state: Kanagawa
city: Tsu
country: Japan
facility: Local Institution - 0246
state: Mie
city: Sendai-shi
country: Japan
facility: Local Institution - 0223
state: Miyagi
city: Suita
country: Japan
facility: Local Institution - 0238
state: Osaka
city: Hidaka
country: Japan
facility: Local Institution - 0227
state: Saitama
city: Ina-machi
country: Japan
facility: Local Institution - 0224
state: Saitama
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0231
state: Tokyo
city: Chuo-ku
country: Japan
facility: Local Institution - 0229
state: Tokyo
city: Koto
country: Japan
facility: Local Institution - 0228
state: Tokyo
city: Shinagawa
country: Japan
facility: Local Institution - 0245
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Local Institution - 0233
state: Tokyo
city: Fukuoka
country: Japan
facility: Local Institution - 0242
city: Fukushima
country: Japan
facility: Local Institution - 0225
city: Hiroshima
country: Japan
facility: Local Institution - 0243
city: Kagoshima
country: Japan
facility: Local Institution - 0244
city: Kyoto
country: Japan
facility: Local Institution - 0235
city: Okayama
country: Japan
facility: Local Institution - 0241
city: Osaka
country: Japan
facility: Local Institution - 0239
city: Goyang-si
country: Korea, Republic of
facility: Local Institution - 0066
state: Kyǒnggi-do
city: Seongnam
country: Korea, Republic of
facility: Local Institution - 0067
state: Kyǒnggi-do
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0068
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0063
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0071
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0064
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0065
state: Seoul-teukbyeolsi [Seoul]
city: Daegu
country: Korea, Republic of
facility: Local Institution - 0069
state: Taegu-Kwangyǒkshi
city: Mexico City
country: Mexico
facility: Local Institution - 0177
state: DIF
city: Guadalajara
country: Mexico
facility: Local Institution - 0178
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution - 0175
state: Nuevo León
city: Oaxaca de Juarez
country: Mexico
facility: Local Institution - 0173
state: Oaxaca
city: Merida
country: Mexico
facility: Local Institution - 0179
state: Yucatán
city: Chihuahua
country: Mexico
facility: Local Institution - 0174
city: Biala Podlaska
country: Poland
facility: Local Institution - 0074
state: Lubelskie
city: Warszawa
country: Poland
facility: Local Institution - 0072
state: Mazowieckie
city: Warszawa
country: Poland
facility: Local Institution - 0220
state: Mazowieckie
city: Opole
country: Poland
facility: Local Institution - 0076
state: Opolskie
city: Skórzewo
country: Poland
facility: Local Institution - 0189
state: Wielkopolskie
city: Łódź
country: Poland
facility: Local Institution - 0221
state: Łódzkie
city: Lisbon
country: Portugal
facility: Local Institution - 0198
state: Lisboa
city: Lisbon
country: Portugal
facility: Local Institution - 0106
state: Lisboa
city: Lisbon
country: Portugal
facility: Local Institution - 0109
state: Lisboa
city: Coimbra
country: Portugal
facility: Local Institution - 0124
city: Lisboa
country: Portugal
facility: Local Institution - 0141
city: Porto
country: Portugal
facility: Local Institution - 0111
city: Porto
country: Portugal
facility: Local Institution - 0253
city: Bistrita
country: Romania
facility: Local Institution - 0212
state: Bistrița-Năsăud
city: Bucharest
country: Romania
facility: Local Institution - 0213
state: București
city: Florești
country: Romania
facility: Local Institution - 0079
state: Cluj
city: Craiova
country: Romania
facility: Local Institution - 0078
state: Dolj
city: Ploiești
country: Romania
facility: Local Institution - 0084
state: Prahova
city: Timișoara
country: Romania
facility: Local Institution - 0085
state: Timiș
city: București
country: Romania
facility: Local Institution - 0083
city: Cluj
country: Romania
facility: Local Institution - 0077
city: Iași
country: Romania
facility: Local Institution - 0081
city: Iași
country: Romania
facility: Local Institution - 0080
city: A Coruña
country: Spain
facility: Local Institution - 0105
state: A Coruña [La Coruña]
city: Elche
country: Spain
facility: Local Institution - 0100
state: Alicante
city: Barcelona
country: Spain
facility: Local Institution - 0102
state: Barcelona [Barcelona]
city: Hospitalet
country: Spain
facility: Local Institution - 0172
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Local Institution - 0140
state: Catalunya [Cataluña]
city: San Sebastian
country: Spain
facility: Local Institution - 0139
state: Gipuzkoa
city: Madrid
country: Spain
facility: Local Institution - 0104
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Local Institution - 0108
state: Madrid, Comunidad De
city: Malaga
country: Spain
facility: Local Institution - 0101
state: Málaga
city: Valencia
country: Spain
facility: Local Institution - 0210
state: Valenciana, Comunitat
city: Madrid
country: Spain
facility: Local Institution - 0107
city: Sevilla
country: Spain
facility: Local Institution - 0103
city: Malmö
country: Sweden
facility: Local Institution - 0252
state: Skåne Län [se-12]
city: Stockholm
country: Sweden
facility: Local Institution - 0026
state: Stockholms Län [se-01]
city: Uppsala
country: Sweden
facility: Local Institution - 0025
state: Uppsala Län [se-03]
city: Örebro
country: Sweden
facility: Local Institution - 0024
state: Örebro Län [se-18]
city: Linköping
country: Sweden
facility: Local Institution - 0247
state: Östergötlands Län [se-05]
city: st.Gallen
country: Switzerland
facility: Local Institution - 0250
state: Sankt Gallen
city: Lausanne
country: Switzerland
facility: Local Institution - 0249
state: Vaud
city: Zürich
country: Switzerland
facility: Local Institution - 0251
city: Abu Dhabi
country: United Arab Emirates
facility: Local Institution - 0323
state: Abū Z̧aby
city: Abu Dhabi
country: United Arab Emirates
facility: Local Institution - 0318
state: Abū Z̧aby
city: Al Ain
country: United Arab Emirates
facility: Local Institution - 0322
state: Abū Z̧aby
city: Abu Dhabi
country: United Arab Emirates
facility: Local Institution - 0319
city: Truro
country: United Kingdom
facility: Local Institution - 0208
state: England
city: London
country: United Kingdom
facility: Local Institution - 0204
state: London, City Of
city: London
country: United Kingdom
facility: Local Institution - 0209
state: London, City Of
city: Belfast
country: United Kingdom
facility: Local Institution - 0171
city: London
country: United Kingdom
facility: Local Institution - 0004
city: Manchester
country: United Kingdom
facility: Local Institution - 0001
city: Nottingham
country: United Kingdom
facility: Local Institution - 0006
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: