Clinical trial NCT03562637: Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC
Official title: The GLORIA Study: A Phase 3, Randomized, Open-Label Study of the Anti-Globo H Vaccine Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With High Risk, Early Stage Globo H-Positive Triple Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Triple Negative Breast Cancer
Keywords: Neoadjuvant chemotherapy
Adjuvant chemotherapy
TNBC
Lead sponsor: OBI Pharma, Inc
Sponsor class: INDUSTRY
First posted: 2018-06-19
Enrollment: 575
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 GLORIA study is a Phase III, randomized, open-label study to prospectively evaluate the efficacy and safety of adagloxad simolenin (OBI 822)/OBI-821 in the adjuvant treatment of patients with high risk, early stage Globo-H Positive TNBC.


Eligibility criteria: Inclusion Criteria:

* Documented radiographic and histopathologic confirmed primary localized invasive breast cancer.
* Histologically documented TNBC (estrogen receptor negative \[ER-\]/progesterone receptor negative \[PR-\]/human epidermal growth factor 2 negative \[HER2-\]) defined as ER-negative and PR-negative (≤5% positive cells stain by IHC for both ER and PR), and negative HER2/neu- status, confirmed on tumor sample.
* HER2/neu negative will be defined as one of the following criteria:

  * IHC 0 or 1+
  * Single-probe average HER2 gene copy number of \<6 signals/nucleus
  * Dual-probe fluorescent in-situ hybridization (FISH) HER2/neu chromosome 17 (CEP17) non-amplified ratio of \<2
* Globo H IHC H-score ≥15 from the residual primary site/or lymph node (if primary site is not available) tumor obtained at time of definitive surgery or initial diagnosis (only if surgical tumor sample is not available). Globo H expression will be determined during pre-screening by Central lab. Instructions for submission of slides/tumor tissue blocks are provided in the protocol and study Lab Manual.
* No evidence of metastatic disease in chest, abdomen and pelvis by CT or other adequate imagining during the Screening Phase. Imaging within 3 months prior to randomization is acceptable as baseline scan. Bone scans and imaging of the brain at screening is optional, and should be symptom directed.
* High risk patients with no evidence of disease after completing standard treatment and meeting ONE of the following criteria:

  * Neoadjuvant chemotherapy followed by definitive surgery: Residual invasive disease following neoadjuvant chemotherapy defined as: A contiguous focus of residual invasive cancer in the surgical breast specimen measuring ≥1 cm in diameter and/or with residual invasive cancer in at least one axillary node (micrometastases or macrometastases), as determined by local pathology review.
  * Definitive surgery followed by adjuvant chemotherapy: Pathological Prognostic Stage IIB, Stage IIIA , Stage IIIB, or Stage IIIC disease according to the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual.
* Must have completed at least 4 cycles of a standard taxane and anthracycline-based multi-agent chemotherapy regimen (or a taxane-only regimen if the patient is ineligible for anthracycline treatment) either in the neoadjuvant or adjuvant setting (e.g., National Comprehensive Cancer Network recommended regimens):.

  * Randomization must occur (a) within 16 weeks after definitive surgery and radiation therapy (if radiation therapy administered) in patients who received neoadjuvant multiagent chemotherapy or, (b) for patients receiving adjuvant multiagent chemotherapy (not including capecitabine, immune checkpoint inhibitor), within 16 weeks after the completion of the adjuvant multiagent chemotherapy and radiation therapy (if radiation therapy administered). Note: patients may be randomized and initiate study treatment concurrent with adjuvant SOC therapy (observation, capecitabine, immune checkpoint inhibitor ± capecitabine).
* Randomization must occur (a) within 16 weeks after definitive surgery and radiation therapy (if radiation therapy administered) in patients who received neoadjuvant multiagent chemotherapy or, (b) for patients receiving adjuvant multiagent chemotherapy (not including capecitabine, immune checkpoint inhibitor), within 16 weeks after the completion of the adjuvant multiagent chemotherapy and radiation therapy (if radiation therapy administered). Note: patients may be randomized and initiate study treatment concurrent with adjuvant SOC therapy (observation, capecitabine, immune checkpoint inhibitor ± capecitabine).
* All treatment-related toxicities resolved to Grade \<1 on National cancer institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0) criteria (except hair loss and ≤Grade 2 neuropathy, which are acceptable).
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
* Females must be either of non-childbearing potential, i.e., surgically sterilized (have documented sterilization, bilateral oophorectomy/salpingectomy at least 3 months before the start of the trial and/or hysterectomy), or one year postmenopausal; or if of childbearing potential must have a negative pregnancy test (urine or serum) at screening.
* Males and females of childbearing potential and their partners must be willing to use effective contraception during the entire Treatment Phase and for at least 4 weeks (28 days) after the last dose of study treatment.
* Adequate hematological, hepatic and renal function as defined below:

  * Absolute neutrophil count (ANC) ≥1,500/µL
  * Platelets ≥75,000/µL
  * Hemoglobin ≥8.5g/dL
  * Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥55 mL/min for subjects with creatinine levels \>1.5 × institutional ULN (glomerular filtration rate can also be used in place of creatinine or creatinine clearance may be calculated per institutional standard)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN
  * Alkaline Phosphatase (ALP) ≤2.5 × ULN
  * Serum total bilirubin ≤1.5 × ULN (unless Gilbert's disease is documented)
* Consent to participate with a signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved patient informed consent for the study prior to beginning any specific study procedures.
* Ability to understand and willingness to complete all protocol required procedures.

Exclusion Criteria:

* Local recurrence of or previous history of ipsilateral or contralateral invasive breast cancer within 10 years prior to randomization \[for synchronous tumors see Exclusion criteria #3\]
* Definitive clinical or radiologic evidence of metastatic disease
* Synchronous bilateral breast cancer, unless both tumors are confirmed as TNBC.
* Have received any anti-cancer vaccines
* Concomitant treatment with anticancer therapy other than adjuvant SOC therapy (capecitabine; immune checkpoint inhibitor), or other investigational therapy, if expected during the study
* A history of other malignancies (except appropriately treated melanoma in situ, non melanoma skin carcinoma, carcinoma in situ of the uterine cervix, follicular or papillary thyroid cancer or other non-breast malignancies with a similar outcome to those mentioned above) within 5 years prior to randomization.
* Have any active autoimmune disease or disorder that requires systemic immunosuppressive/immunomodulatory therapy. NOTE: Autoimmune diseases that are confined to the skin (e.g., psoriasis) that can be treated with topical steroids alone are allowed during the study.
* Oral/parenteral corticosteroid treatment (\>5 mg/day of prednisone/equivalent), within 2 weeks prior to randomization or anytime during the study. NOTE: inhaled steroids for treatment of asthma; and topical steroids are allowed during the study.
* Any known uncontrolled concurrent illness that would limit compliance with study requirements, including but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric disorders, or substance abuse.
* Any known hypersensitivity to active/inactive ingredients in the study drug formulation or known severe allergy or anaphylaxis to fusion proteins.
* Prior receipt of a glycoconjugate vaccine for cancer immunotherapy.
* Known history or positive for human immunodeficiency virus (HIV positive), unless on effective anti-retroviral therapy with undetectable viral load within 6 months of therapy (note: HIV testing not required for study entry).
* Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to randomization. Patients who have completed curative therapy and have undetectable viral load for HCV are eligible. For patients with evidence of chronic HBV infection, the HBV viral load must be undetectable on suppressive therapy. (note: HBV/HCV testing is not required for study entry).
* Any condition, including significant diseases and/or laboratory abnormalities that would place the patient at unacceptable risk for study participation.
* Currently pregnant or breastfeeding women.
* Currently participating in or has participated in a breast cancer therapeutic clinical trial within 4 weeks (28 days) prior to randomization.

Primary outcomes:
measure: Measuring the effect of adagloxad simolenin (OBI-822)/OBI-821 treatment on improving invasive disease free survival (IDFS) in the study population.
timeFrame: 5 years
Secondary outcomes:
measure: Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Overall Survival (OS).
timeFrame: 7 years
measure: Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Quality of Life (QoL).
timeFrame: 7 years
measure: Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Breast cancer-free interval (BCFI).
timeFrame: 7 years
measure: Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Distant disease-free survival (DDFS).
timeFrame: 7 years
measure: Incidence and severity of adverse events (AEs) [Time Frame: AEs will be noted as it occurs, with a timeframe from beginning of randomization to 4 weeks after last dose of study treatment.]
timeFrame: 2 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Centre
state: California
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland Greenbaum Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Midlothian
country: United States
facility: Bons Secours St. Francis Medical Oncology Center
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Urraween
country: Australia
facility: Cancer Care Service, Hervey Bay Hospital
state: Queensland
city: East Melbourne
country: Australia
facility: Victoria Breast & Oncology Care
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Malvern
state: Victoria
city: Nedlands
country: Australia
facility: Breast Cancer Research Centre
state: Western Australia
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
city: Gosford
country: Australia
facility: Gosford Hospital
city: Murdoch
country: Australia
facility: St John of God Murdoch Hospital
city: Ringwood East
country: Australia
facility: Eastern Health - Maroondah Hospital
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
state: Bahia
city: Fortaleza
country: Brazil
facility: Suporte Nutricional e Quimioterapia
state: Ceara
city: Serra
country: Brazil
facility: Centro de Avaliacao de Medicamentos e Especialidades de Pesquisa
state: Espirito Santo
city: Belo Horizonte
country: Brazil
facility: Instituto Mario Penna
state: Minas Gerais
city: Campo Largo
country: Brazil
facility: Maternidade e Cirurgia Nossa Senhora do Rocio
state: Parana
city: Curitiba
country: Brazil
facility: Hospital das Clinicas - Universidade Federal do Parana
state: Parana
city: Belém
country: Brazil
facility: Centro de Tratamento Oncologico LTDA - CTO
state: Para
city: Recife
country: Brazil
facility: Hospital do Capibaribe
state: Pernambuco
city: Recife
country: Brazil
facility: Real Hospital Portugues de Beneficencia de Pernambuco
state: Pernambuco
city: Teresina
country: Brazil
facility: Centro de Pesquisa Vencer & Oncolinca
state: Piaui
city: Barretos
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Ijuí
country: Brazil
facility: Oncosite-Centro de Pesquisa Clinica em Oncologia
state: Rio Grande Do Sul
city: Pelotas
country: Brazil
facility: Hospital Escola da Universidade Federal de Pelotas
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) - Hospital Sao Lucas
state: Rio Grande Do Sul
city: Porto Velho
country: Brazil
facility: Hospital de Amor Amazonia
state: Rondona
city: Boa Vista
country: Brazil
facility: Centro Oncologico de Roraima
state: Roraima
city: Chapeco
country: Brazil
facility: Clinica Supera
state: Santa Catarina
city: Itajaí
country: Brazil
facility: Clinica de Neoplasias Litoral - Itajai
state: Santa Catarina
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: Sao Paulo
city: Jaú
country: Brazil
facility: Hospital Amaral Carvalho de Jau
state: Sao Paulo
city: Santo André
country: Brazil
facility: Centro de Pesquisa Clinica em Hematologia e Oncologia
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Clinicia de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Instituto Brasileiro de Controle do Cancer
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Instituto do Cancer do Estado de San Paulo
state: Sao Paulo
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Beijing
country: China
facility: Cancer Institute and Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Saltillo
country: Mexico
facility: Clinica Oncor - Centro de Infusion e Investigacion Oncologia de Satillo
state: Coahuila
city: Ciudad de mexico
country: Mexico
facility: Instituto Nacional de Cancerologia
state: Del Tialpan
city: Toluca
country: Mexico
facility: Centro Oncologico Estatal Instituto de Seguridad Social del Estado de Mexico y Municipios
state: Estado De Mexico
city: Zapopan
country: Mexico
facility: Investigacion Biomedica para el Desarrollo de Farmacos
state: Jalisco
city: Morelia
country: Mexico
facility: Sociedad Administradora de Servicios de Salud S.C.
state: Michoacan
city: San Pedro Garza Garcia
country: Mexico
facility: Centro Medico Zambrano Hellion
state: Nuevo Leon
city: Aguascalientes
country: Mexico
facility: Investigacion Biomedica para el Desarrollo de Farmacos, S.A. de. C.V
city: Chihuahua
country: Mexico
facility: Centro Estatal de Cancerologia
city: Chihuahua
country: Mexico
facility: Icaro Investigaciones en Medicina S.A. de C.V.
city: Chihuahua
country: Mexico
facility: Scientia Investigacion Clinica S.C.
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas
state: Surquillo
city: Arequipa
country: Peru
facility: Instituto Regional de Enfermedades Neoplasicas del Sur
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati Martins, Unidad de Investigacion de Oncologia Medica
city: Lima
country: Peru
facility: Unidad de Investigacion - Oncologia Medica Clinica San Felipe
city: Lima
country: Peru
facility: Hospital Maria Auxiliadora
city: Gdańsk
country: Poland
facility: University Clinical Centre - Hospital, Teaching Dept of Oncology and Radiotherapy
city: Kraków
country: Poland
facility: Independent Public Healthcare Facility University Hospital in Cracow
city: Warsaw
country: Poland
facility: Central Teaching Hospital of the MOI in Warsaw
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie National Institute of Oncology
city: Łódź
country: Poland
facility: Contemporary Therapy Centre
city: Łódź
country: Poland
facility: Polish Mother's Memorial Hospital Research Instistute
city: Saransk
country: Russian Federation
facility: Nat. Research Mordovia State University
state: Republic Of Mordovia
city: Arkhangelsk
country: Russian Federation
facility: SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Territorial Clinical Oncology Center named after A.I. Kryzhanovsky
city: Moscow
country: Russian Federation
facility: FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
city: Moscow
country: Russian Federation
facility: SBIH of Moscow city "Moscow city oncology hospital №62" of Moscow Healthcare department
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical Oncology Dispensary"
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncological Center
city: Pesochnyy
country: Russian Federation
facility: N.N. Petrov National Medical Research Center of Oncology
city: Saint Petersburg
country: Russian Federation
facility: LLC Medaid
city: Saint-Petersburg
country: Russian Federation
facility: SPb SBIH "City Clinical Oncological Dispensary"
city: St. Petersburg
country: Russian Federation
facility: Klinika Luch, Ltd.
city: Volzhskiy
country: Russian Federation
facility: SBHI "Volgograd Regional Oncology Dispensary #3"
city: Yaroslavl
country: Russian Federation
facility: SBIH of Yaroslavl region "Regional Clinical Oncological Hospital"
city: Johannesburg
country: South Africa
facility: Netcare Milpark Hospital
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Clinical Research, a division of Wits Health Consortium (Pty) Ltd
state: Gauteng
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
state: Gauteng
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Chang Gung Medical Foundation Linkou
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine
city: Dnipro
country: Ukraine
facility: City Clinical Hospital #4
city: Ivano-Frankivsk
country: Ukraine
facility: CI Transcarpathian Cl Onc Center Dep of Surgery#1 SHEI Ivano-Frankivsk NMU
city: Kharkiv
country: Ukraine
facility: CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection
city: Kherson
country: Ukraine
facility: CI of Kherson Reg Council Kherson Regional Oncologic Dispensary
city: Kyiv
country: Ukraine
facility: Medical Center of Vision Partner
city: Kyiv
country: Ukraine
facility: Medical Center Verum
city: Kyiv
country: Ukraine
facility: Kyiv Сity Clinical Oncological Center
city: Zhytomyr
country: Ukraine
facility: CI Reg. Oncol. Dispanser
Study officials:
affiliation: University of California, San Francisco
name: Hope Rugo, MD
role: STUDY_CHAIR
References:
citation: Rugo HS, Cortes J, Barrios CH, Cabrera P, Xu B, Huang CS, Kim SB, Melisko M, Nanda R, Pienkowski T, Rapoport BL, Schwab R. GLORIA: phase III, open-label study of adagloxad simolenin/OBI-821 in patients with high-risk triple-negative breast cancer. Future Oncol. 2022 Oct 21. doi: 10.2217/fon-2022-0812. Online ahead of print.