| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Triple Negative Breast Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10075566 |
| E.1.2 | Term | Triple negative breast cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To determine the effect of adagloxad simolenin (OBI-822)/OBI-821 treatment on improving invasive disease-free survival (IDFS) in the study population. |
|
| E.2.2 | Secondary objectives of the trial |
1. To determine the impact of adagloxad simolenin (OBI-822)/OBI-821 treatment in the study population, on:
a. Overall survival (OS)
b. Quality of Life (QoL)
c. Breast cancer-free interval (BCFI)
d. Distant disease-free survival (DDFS)
2. To determine safety and tolerability of adagloxad simolenin (OBI-822)/OBI-821 in the study population. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female patient ≥18 years.
2. Documented radiographic and histopathologic confirmed primary localized invasive breast cancer.
3. Histologically documented TNBC (estrogen receptor-negative [ER-] / progesterone receptor-negative [PR-] / human epidermal growth factor 2-negatove [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
4. Globo H IHC H-score ≥15 from the residual primary site/or lymph node (if primary site is not available) tumor obtained at the 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.
5. No evidence of metastatic disease in chest, abdomen, and pelvis by CT or other adequate imaging 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.
6. 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, IIIB, or Stage IIIC disease according to the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual.
7. 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).
8. 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, 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 (capecitabine).
9. All treatment-related toxicities resolved to Grade <1 on National Cancer
Institute-Common Terminology Criteria for Adverse Events (version 5.0) criteria (except hair loss and ≤Grade 2 neuropathy, which are acceptable).
10. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
11. 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.
12. Males and females of childbearing potential and their partners must be willing to use effective contraception during the entire study Treatment Phase (Section 9.4.7) and for at least 4 weeks (28 days) after the last dose of study treatment.
13. Adequate hematological, hepatic and renal function as defined below:
- Absolute neutrophil count (ANC) ≥1,500/μL
- Platelets ≥75,000/μL
- Hemoglobin ≥8.5 g/dL
- Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine
clearance ≥55 mL/min for patients 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).
14. Consent to participate with a signed and dated Institutional Review Board /Independent Ethics Committee -approved patient informed consent for the study prior to beginning any specific study procedures.
15. Ability to understand and willingness to complete all protocol required procedures. |
|
| E.4 | Principal exclusion criteria |
1. Local recurrence of or previous history of any ipsilateral or contralateral invasive breast cancer within 10 years prior to randomization [for synchronous tumors see Exclusion Criteria #3].
2. Definitive clinical or radiologic evidence of metastatic disease.
3. Synchronous bilateral breast cancer, unless both tumors are confirmed as TNBC.
4. Have received any post-operative immunotherapy with antigen, antibody, immune checkpoint inhibitors (Programmed cell death-1 [PD-1]/ Programmed cell deathligand- 1 [PD-L-1] inhibitors, 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).
5. Concomitant treatment with anticancer therapy other than adjuvant SOC therapy (capecitabine), or other investigational therapy, if expected during the study.
6. 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.
7. 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.
8. 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.
9. 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.
10. Any known hypersensitivity to active/inactive ingredients in the study drug
formulation or known severe allergy or anaphylaxis to fusion proteins.
11. Prior receipt of a glycoconjugate vaccine for cancer immunotherapy.
12. 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 is not required for study entry).
13. 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).
14. Any condition, including significant diseases and/or laboratory abnormalities that would place the patient at unacceptable risk for study participation.
15. Currently pregnant or breastfeeding women.
16. Currently participating in or has participated in a breast cancer therapeutic clinical trial within 4 weeks (28 days) prior to randomization. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
IDFS (Invasive Disease Free Survival), defined by STEEP, as time from randomization to the date of first invasive disease recurrence (local, regional or distant), date of second invasive primary cancer (breast or not), or date of death from any cause, whichever occurs first.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Every 8 weeks, starting at Study Week 28 through 92; at Wk104 and then every 26 weeks starting at Study Wk 126 through 256. |
|
| E.5.2 | Secondary end point(s) |
- OS status
- Change from baseline in health-related quality of life (HRQOL) using the global health status/QoL scale from EORTC QLQ-C30 and EQ-5D-5L questionnaires
- Breast cancer-free interval (BCFI)
- Distant disease-free survival (DDFS)
- Incidence of AEs and SAEs, incidence of abnormal laboratory values, and change from baseline in safety parameters. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Same point as above Primary Endpoint, unless the specific assessment is not scheduled |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 9 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Peru |
| Ukraine |
| Hong Kong |
| Taiwan |
| Australia |
| Brazil |
| China |
| Korea, Republic of |
| Mexico |
| Russian Federation |
| South Africa |
| United States |
| Germany |
| Poland |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of study is defined as completion of all study required procedures. Disease recurrence, if applicable and survival data will be collected and subject will exit the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 14 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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