Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC

Triple Negative Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03562637
• Other study ID #: OBI-822-011
• Status: Recruiting
• Phase: Phase 3
• Start date: December 5, 2018
• Est. completion date: December 30, 2027

Study information

• Verified date: February 2024
• Source: OBI Pharma, Inc
• Contact: OBI Pharma CT.gov Assistant
• Phone: 1-619-537-7821
• Email: ClinicalTrials.gov-queries[@]obipharmausa.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 668
• Est. completion date: December 30, 2027
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. 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 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 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 a standard taxane, and/or anthracycline-based multi-agent chemotherapy regimen either in the neoadjuvant or adjuvant setting (e.g., National Comprehensive Cancer Network recommended regimens):.

• At least 4 cycles of a standard multi-agent chemotherapy regimen must have been received, unless precluded by toxicities

• Post operative adjuvant capecitabine or a platinum monotherapy in patients with residual disease after neoadjuvant chemotherapy is allowed.

• Randomization must occur within 12 weeks after completion of standard of care treatment (surgery and/or chemotherapy) and within 46 weeks from the date of definitive surgery. Note: patients receiving adjuvant capecitabine or platinum monotherapy after neoadjuvant multi-agent chemotherapy may be randomized and initiate study treatment during (or within 12 weeks after completion of) the adjuvant capecitabine or platinum monotherapy.

• 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 of 0 or 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 randomization.

• Males and females of childbearing potential and their partners must be willing to use effective contraception during the entire Treatment Phase period 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.

• Definitive clinical or radiologic evidence of metastatic disease

• Synchronous bilateral breast cancer, unless both tumors are confirmed as TNBC.

• Have received any post-operative immunotherapy with antigen, antibody, immune checkpoint inhibitors (Programmed cell death-1 [PD-1]/ Programmed cell death-ligand-1inhibitors [PD-L-1], anti-cytotoxic T lymphocyte associated protein 4 [CTLA 4] therapy), or other anti-cancer vaccines (neoadjuvant receipt of immune checkpoint inhibitors will not be exclusionary if the patient meets all other eligibility criteria).

• Concomitant treatment with approved anticancer therapy or immunotherapy including checkpoint inhibitors (e.g. PD-1 inhibitors) or other investigational therapy, if expected during the study. Adjuvant capecitabine or platinum monotherapy is allowed during the study.

• A history of other malignancies (except non melanoma skin carcinoma, carcinoma in situ of the uterine cervix, follicular or papillary thyroid cancer) 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 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 (24 days) prior to randomization.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Biological:
• adagloxad simolenin combined with OBI-821
In the neoadjuvant and adjuvant phases of the study for a total of 100 weeks; subcutaneously injections.

Device:
• Globo H IHC Assay
The Globo H IHC assay will be used to identify eligible patients who may clinically benefit from the OBI-822 treatment, defined by Globo H expression.

Other:
• Standard of care treatment
Standard of care treatment consisting of observation alone, adjuvant capecitabine or platinum monotherapy over a 100 week period.

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Sydney	Darlinghurst
Australia	Slade Pharmacy	East Melbourne	Victoria
Australia	Gosford Hospital	Gosford
Australia	Cabrini Malvern	Malvern	Victoria
Australia	St John of God Murdoch Hospital	Murdoch
Australia	Breast Cancer Research Centre	Nedlands	Western Australia
Australia	Eastern Health - Maroondah Hospital	Ringwood East
Australia	Cancer Care Service, Hervey Bay Hospital	Urraween	Queensland
Australia	Westmead Hospital	Westmead	New South Wales
Brazil	Hospital de Cancer de Barretos	Barretos	Sao Paulo
Brazil	Hospital de Clinicas de Porto Alegre	Barretos	Rio Grande Do Sul
Brazil	Centro de Tratamento Oncologico LTDA - CTO	Belém	Para
Brazil	Instituto Mario Penna	Belo Horizonte	Minas Gerais
Brazil	Centro Oncologico de Roraima	Boa Vista	Roraima
Brazil	Maternidade e Cirurgia Nossa Senhora do Rocio	Campo Largo	Parana
Brazil	Clinica Supera	Chapeco	Santa Catarina
Brazil	Suporte Nutricional e Quimioterapia	Fortaleza	Ceara
Brazil	Oncosite-Centro de Pesquisa Clinica em Oncologia	Ijuí	Rio Grande Do Sul
Brazil	Clinica de Neoplasias Litoral - Itajai	Itajaí	Santa Catarina
Brazil	Hospital Amaral Carvalho de Jau	Jaú	Sao Paulo
Brazil	Hospital Escola da Universidade Federal de Pelotas	Pelotas	Rio Grande Do Sul
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) - Hospital Sao Lucas	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Amor Amazonia	Porto Velho	Rondona
Brazil	Hospital do Capibaribe	Recife	Pernambuco
Brazil	Real Hospital Portugues de Beneficencia de Pernambuco	Recife	Pernambuco
Brazil	Hospital Sao Rafael	Salvador	Bahia
Brazil	Centro de Pesquisa Clinica em Hematologia e Oncologia	Santo André	Sao Paulo
Brazil	Clinicia de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria	São Paulo	Sao Paulo
Brazil	Instituto Brasileiro de Controle do Cancer	São Paulo	Sao Paulo
Brazil	Instituto do Cancer do Estado de San Paulo	São Paulo	Sao Paulo
Brazil	Centro de Avaliacao de Medicamentos e Especialidades de Pesquisa	Serra	Espirito Santo
Brazil	Centro de Pesquisa Vencer & Oncolinca	Teresina	Piaui
China	Cancer Hospital CAMS	Beijing	Beijing
China	Cancer Institute and Hospital	Beijing
China	Peking University Cancer Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	The First Hospital of Guangxi Medical University	Nanning	Guangxi
China	Liaoning Cancer Hospital and Institute	Shenyang	Liaoning
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	Hubei Cancer Hospital	Wuhan	Hubei
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	The University of Hong Kong	Hong Kong
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si
Mexico	Icaro Investigaciones en Medicina S.A. de C.V.	Chihuahua
Mexico	Instituto Nacional de Cancerologia	Ciudad de mexico	Del Tialpan
Mexico	Clinica Oncor - Centro de Infusion e Investigacion Oncologia de Satillo	Saltillo	Coahuila
Mexico	Centro Medico Zambrano Hellion	San Pedro Garza Garcia	Nuevo Leon
Peru	Instituto Regional de Enfermedades Neoplasicas del Sur	Arequipa
Peru	Hospital Nacional Edgardo Rebagliati Martins, Unidad de Investigacion de Oncologia Medica	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima	Surquillo
Peru	Unidad de Investigacion - Oncologia Medica Clinica San Felipe	Lima
Poland	University Clinical Centre - Hospital, Teaching Dept of Oncology and Radiotherapy	Gdansk
Poland	Independent Public Healthcare Facility University Hospital in Cracow	Kraków
Poland	Contemporary Therapy Centre	Lódz
Poland	Polish Mother's Memorial Hospital Research Instistute	Lódz
Poland	Central Teaching Hospital of the MOI in Warsaw	Warsaw
Poland	Maria Sklodowska-Curie National Institute of Oncology	Warsaw
Russian Federation	SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"	Arkhangelsk
Russian Federation	LLC Evimed	Chelyabinsk
Russian Federation	Krasnoyarsk Territorial Clinical Oncology Center named after A.I. Kryzhanovsky	Krasnoyarsk
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow
Russian Federation	SBIH of Moscow city "Moscow city oncology hospital ?62" of Moscow Healthcare department	Moscow
Russian Federation	SBIH of Nizhniy Novgorod region	Nizhny Novgorod
Russian Federation	BHI of Omsk region "Clinical Oncology Dispensary"	Omsk
Russian Federation	Orenburg Regional Clinical Oncological Center	Orenburg
Russian Federation	FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"	Pesochnyy
Russian Federation	N.N. Petrov National Medical Research Center of Oncology	Pesochnyy
Russian Federation	LLC Medaid	Saint Petersburg
Russian Federation	SPb SBIH "City Clinical Oncological Dispensary"	Saint-Petersburg
Russian Federation	Nat. Research Mordovia State University	Saransk	Republic Of Mordovia
Russian Federation	Klinika Luch, Ltd.	St. Petersburg
Russian Federation	SI "SRI of Oncology of Tomsk RC of Siberian Branch of RAMS"	Tomsk
Russian Federation	SBHI "Volgograd Regional Oncology Dispensary #3"	Volzhskiy
Russian Federation	SBIH of Yaroslavl region "Regional Clinical Oncological Hospital"	Yaroslavl
South Africa	Medical Oncology Centre of Rosebank	Johannesburg	Gauteng
South Africa	Netcare Milpark Hospital	Johannesburg	Gauteng
South Africa	Wits Clinical Research, a division of Wits Health Consortium (Pty) Ltd	Johannesburg	Gauteng
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chung Shan Medical University	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Chang Gung Memorial Hospital, Taipei	Taipei
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Ukraine	City Clinical Hospital #4	Dnipro
Ukraine	Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine	Dnipro
Ukraine	CI Transcarpathian Cl Onc Center Dep of Surgery#1 SHEI Ivano-Frankivsk NMU	Ivano-Frankivsk
Ukraine	CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection	Kharkiv
Ukraine	Grigoriev Institute for Medical Radiology and Oncology of the NAMSU	Kharkiv
Ukraine	Regional Center of Oncology	Kharkiv
Ukraine	CI of Kherson Reg Council Kherson Regional Oncologic Dispensary	Kherson
Ukraine	CI Kryvyi Rih Oncological Dispensary of DRC	Kryvyi Rih
Ukraine	First Private Clinic	Kyiv
Ukraine	Kyiv ?ity Clinical Oncological Center	Kyiv
Ukraine	Medical Center of Vision Partner	Kyiv
Ukraine	Medical Center Verum	Kyiv
Ukraine	Treatment-Prevention Institution Volyn Regional Oncological Dispensary	Lutsk
Ukraine	Odesa Regional Oncologic Dispensary	Odesa
Ukraine	CI Zaporizhzhia Regional Clinical Oncological Dispensary of ZRC	Zaporizhzhia
Ukraine	CI Reg. Oncol. Dispanser	Zhytomyr
United States	University of Maryland Greenbaum Comprehensive Cancer Center	Baltimore	Maryland
United States	University of Chicago Medical	Chicago	Illinois
United States	Henry Ford Medical Center	Detroit	Michigan
United States	Moores UCSD Cancer Center	La Jolla	California
United States	Miami Cancer Institute	Miami	Florida
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente Medical Center	San Diego	California
United States	UCSF Helen Diller Family Comprehensive Cancer Centre	San Francisco	California
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	North Mississippi Medical Center Hematology and Oncology Clinic	Tupelo	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
OBI Pharma, Inc

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  China,  Hong Kong,  Korea, Republic of,  Mexico,  Peru,  Poland,  Russian Federation,  South Africa,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measuring the effect of adagloxad simolenin (OBI-822)/OBI-821 treatment on improving invasive disease free survival (IDFS) in the study population.	The outcome measure of the study is IDFS, defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of first invasive disease recurrence (local, regional or distant), the date of secondary primary invasive cancer (breast or not), or the date of death from any cause.	5 years
Secondary	Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Overall Survival (OS).	OS is defined as the time from randomization to date of death from any cause	7 years
Secondary	Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Quality of Life (QoL).	QoL defined as time to definitive deterioration in Health-related Quality of Life (HRQOL) using the global health status/QoL scale from European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L). QoL baseline established at randomization.; Definitive deterioration defined as a 5% worsening relative to baseline in the HRQOL scale score from EORTC QLQ-C30 questionnaires with no subsequent improvement above threshold, scored with the EORTC QLQ-C30 v3.0 Scoring Manual. The EQ-5D-5L questionnaire assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, rated by the patient. It is a standardized measure of health status to provide a simple, generic measure of health for clinical and economic appraisal. 28 questions have a 4 point scale: not at all(1) to very much(4). 2 questions have a 7-point scale: very poor (1) to excellent(7).	7 years
Secondary	Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Breast cancer-free interval (BCFI).	BCFI is defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of the first invasive disease recurrence (local, regional or distant), the date of ductal carcinoma in situ (ipsilateral or contralateral), or the date of death from breast cancer	7 years
Secondary	Measuring the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population on Distant disease-free survival (DDFS).	DDFS is defined by the STEEP system as the first occurrence of the time from the date of randomization to the date of the first distant disease recurrence, the date of the second primary invasive cancer (non-breast), or the date of death from any cause	7 years
Secondary	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.]	Adverse Events will be graded and recorded by investigators per National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0).	2 years