Trial Title:
Personalised Neoantigen-targeting Cancer Vaccine NECVAX-NEO1 in Neoadjuvant Triple-negative Breast Cancer
NCT ID:
NCT06631092
Condition:
Triple Negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Oral DNA Vaccine
Description:
Bacteria-based orally administered personalised neoantigen-targeting cancer vaccine
Arm group label:
NECVAX-NEO1
Summary:
Phase I/II, multicenter, open-label, single-arm trial in triple-negative breast cancer
patients under first-line neoadjuvant therapy with approved standard of care anti-PD-1
monoclonal antibody (PD-1 inhibitor), epirubicin/cyclophosphamide chemotherapy, and
nab-paclitaxel therapy. NECVAX-NEO1 treatment in addition to standard of care anti-PD1
monoclonal antibody therapy can be prolonged after breast cancer surgery for another 24
weeks, according to the investigator's decision taking into consideration the study
patient's health status.
Detailed description:
Phase I/II, multicenter, open-label, single-arm trial in triple-negative breast cancer
patients under first-line neoadjuvant therapy with approved standard of care anti-PD-1
monoclonal antibody (PD-1 inhibitor), epirubicin/cyclophosphamide chemotherapy, and
nab-paclitaxel therapy. Optionally, NECVAX-NEO1 treatment in addition to standard of care
anti-PD1 monoclonal antibody therapy can be prolonged after breast cancer surgery for
another 24 weeks, according to the investigator's decision taking into consideration the
study patient's health status.
Personalized NECVAX-NEO1 constructs containing an eukaryotic expression plasmid encoding
a series of selected neoantigen epitopes will be manufactured for administration as a
patient-specific investigational medicinal product (IMP). The IMP will be administered
and as an add-on therapy to the standard of care PD-1 inhibitor therapy.
The trial will consist of mainly:
- A Screening and Induction period of up to 12 weeks, including the neoantigen
selection and manufacturing phase, and first-line treatment with PD-1 inhibitor
therapy with epirubicin 90 mg/m2/cyclophosphamide 600 mg/m2 every 3 weeks combined
with pembrolizumab 200 mg as standard of care treatment,
- A Treatment period of up to 12 weeks with prime and booster administrations of
NECVAX-NEO1 in addition to continuation of PD-1 inhibitor pembrolizumab 200 mg every
3 weeks and nab-paclitaxel 125 mg/m2 once a week for 12 weeks up to planned tumor
surgery,
- An optional prolongation of booster administration of NECVAX-NEO1 in addition to
continuation of PD-1 inhibitor up to 24 weeks, and
- A Follow-up period of 4 weeks, with an End of Treatment (EoT) visit at Week 16 or at
Week 40 (in case of the optional treatment prolongation).
- A long-term safety follow-up period (observation period) after EoT for up to 24
months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients able to understand and follow instructions during the trial.
2. Patients able and willing to give written informed consent, signed and dated.
3. Female and male patients.
4. Patients aged at least 18 years old at the time of ICF signature.
5. cT2-4 N0 or any N-positive (stage II-III) triple-negative breast cancer patients
diagnosed as candidates for neoadjuvant anti-PD1 monoclonal antibody and
anthracycline/taxane based chemotherapy
6. Patients with tumor accessible for biopsy and surgery and showing at least 30% of
tumoral cells on the biopsy.
7. Patients with adequate bone marrow function at Screening, confirmed at Baseline,
including:
1. ANC ≥ 1.5 × 109/L; patients with documented benign cyclical neutropenia are
eligible if white blood cell count is ≥ 1.5 × 109/L, with ANC ≥ 1.0 × 109/L,
leukocytes ≥ 4.0 × 109/L, and lymphocytes ≥ 0.6 × 109/L;
2. platelets ≥ 100 × 109/L;
3. hemoglobin ≥ 9 g/dL (may have been transfused);
8. International Normalized Ratio (INR) < 1.5×Upper Limit of Normal (ULN); patients
treated with vitamin K antagonist are eligible if INR < 3.
9. Patients with adequate hepatic function at Screening, confirmed at Baseline, defined
by
1. total bilirubin level ≤1.5×ULN; patients with documented Gilbert disease are
allowed if total bilirubin ≤3×ULN;
2. aspartate aminotransferase (AST) level ≤2.5×ULN, and alanine aminotransferase
(ALT) level ≤2.5×ULN, or, for patients with documented metastatic disease to
the liver, AST and ALT levels ≤5×ULN.
10. Patients with adequate renal function at Screening, confirmed at Baseline, defined
by eGFR ≥ 30 mL/min using 2021 CKD-EPI creatinine equation.
11. Patients must be able to undergo MRI/Ultrasound imaging procedures for tumor
follow-up.
12. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
13. Life expectancy of at least 12 months according to the Investigator's judgement.
Exclusion Criteria:
Medical and surgical history, and diseases
1. Patients with a history of any disease, metabolic dysfunction, physical examination
finding, or clinical laboratory finding that, based on the Investigator's judgement,
provides a reasonable suspicion of a disease or condition that contraindicates the
use of the IMP or that might affect the interpretation of the trial results or
render the patient at high risk for treatment complications.
2. Patients with CTCAE v 5.0 Grade 3 or higher not having resolved to Grade 1 within 6
weeks before Baseline.
3. Patients with any significant co-morbidity which, according to the Investigator's
judgement, makes patient compliance to trial conditions unlikely.
4. Patients with previous malignant disease (other than the tumor disease for this
trial) within the last five (5) years (except adequately treated non-melanoma skin
cancers and carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or
prostate) unless a complete remission without further recurrence was achieved at
least two (2) years prior to Screening, and the patient is deemed to have been cured
with no additional therapy required or anticipated to be required.
5. Patients who underwent prior organ transplantation, including allogeneic stem cell
transplantation.
6. Patients with congenital or any other immunodeficiency syndromes, or any active
autoimmune disease that might deteriorate when receiving an immunostimulatory agent,
except for:
a. Patients with vitiligo, psoriasis, alopecia not requiring immunosuppressive
treatment, are eligible.
b. Administration of steroids through a route known to result in a minimal systemic
exposure (topical, intranasal, intro-ocular, or inhalation), is acceptable.
7. Patients with history of uncontrolled intercurrent illness, including but not
limited to uncontrolled hypertension (high blood pressure defined as BPD>=140 mmHg
or BPS >=90 mmHg despite of combination therapy with diuretic/CCB/ACE or ARB).
8. Patients with a known prior hypersensitivity or contraindications to any of the IMPs
or any component in its formulations or any other drug scheduled or likely to be
given during the trial, including known severe hypersensitivity reactions to
monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3).
9. Patients with severe acute or chronic medical conditions, including
1. Immune colitis
2. Inflammatory bowel disease
3. History of severe vomiting or diarrhea not having resolved to Grade 1 at
Baseline
4. Immune pneumonitis
5. Pulmonary fibrosis
6. Psychiatric conditions including recent (within the last year) or active
suicidal ideation or behavior
7. Laboratory abnormalities that may increase the risk associated with trial
participation or trial treatment administration or may interfere with the
interpretation of trial results and, in the judgement of the Investigator,
would make the patient inappropriate for entry into this trial.
10. Patients with a history of small intestine resection surgery or other major
gastrointestinal surgery
11. Patients with active infection requiring systemic therapy with antibiotics (at both
Screening and Baseline).
12. Patients with a known history of human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome or multi-drug resistant gram-negative bacteria.
13. Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at
Screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody Screening
test positive).
14. Patients with increased anesthesiological risk (e.g. known or predicted difficult
airway) if general anesthetic is required .
15. Patients with increased bleeding risk (e.g. coagulopathies) and patients on
anticoagulants.
16. Women who are pregnant or breastfeeding, or women of childbearing potential (defined
as any woman who is not surgically sterile with a hysterectomy and/or bilateral
oophorectomy or ≥ 12 months of amenorrhea and at least 50 years of age) not willing
to use highly effective methods of birth control. Highly effective birth control is
defined as follows:
1. combined (estrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation 1: • oral
• intravaginal
• transdermal
2. progestogen-only hormonal contraception associated with inhibition of ovulation
1: • oral
• injectable
- implantable 2
3. intrauterine device (IUD) 2
4. intrauterine hormone-releasing system (IUS) 2
5. bilateral tubal occlusion 2
6. vasectomised partner 2,3
7. sexual abstinence 4
NOTES:
1. Hormonal contraception may be susceptible to interaction with the IMP, which may
reduce the efficacy of the contraception method (see section 4.3)
2. Contraception methods that in the context of this guidance are considered to have
low user dependency.
3. Vasectomised partner is a highly effective birth control method provided that
partner is the sole sexual partner of the WOCBP trial participant and that the
vasectomised partner has received medical assessment of the surgical success.
4. In the context of this guidance sexual abstinence is considered a highly effective
method only if defined as refraining from heterosexual intercourse during the entire
period of risk associated with the study treatments. The reliability of sexual
abstinence needs to be evaluated in relation to the duration of the clinical trial
and the preferred and usual lifestyle of the subject.
Males of child-bearing potential are to use a highly effective method of birth control to
avoid pregnancy with any partner during the study and until the end of the Follow-up
period (EoT) or 30 calendar days after the last dose of IMP.
17. Patients with a known history of drug/substance abuse.
Prior and concomitant medication
18. Patients who received any live vaccines within 30 days prior to trial treatment.
19. Patients participating Treatment in any other clinical trial within 30 days before
Screening.
20. Patients receiving any other treatment that, in the opinion of the Investigator,
might interfere with the trial
21. Patients with a current drug or substance abuse.
22. Patients with chronic concurrent therapy within 2 weeks before the trial treatment
or expected therapy during the trial treatment period with:
1. Corticosteroids (except systemic corticosteroids up to 10 mg prednisolone or
equivalent daily dose).
2. Immunosuppressive agents.
3. Antibiotics. Any other anticancer therapy or concurrent anticancer treatment except
the neoadjuvant chemotherapy / anti-PD1 checkpoint inhibitor standard of care
background therapy as per study protocol.
Other 23. Patients unable to understand the Protocol requirements, instructions and
trial-related restrictions, the nature, scope, and possible consequences of the trial.
24. Patients who are unlikely to comply with the Protocol requirements, instructions and
trial-related restrictions, e.g., uncooperative attitude, inability to return for
follow-up visits, and improbability of completing the trial.
25. Patients with legal incapacity or limited legal capacity. 26. Patients with any
condition which results in an undue risk for the patient during the trial
participation according to the Investigator.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University Clinic Erlangen
Address:
City:
Erlangen
Country:
Germany
Status:
Recruiting
Contact:
Last name:
NEC Bio Therapeutics
Phone:
0049 950499
Phone ext:
50
Email:
info@nec-bio.com
Facility:
Name:
National Center for Tumor Diseases Heidelberg
Address:
City:
Heidelberg
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
NEC Bio Therapeutics
Phone:
0049 950499
Phone ext:
50
Email:
info@nec-bio.com
Facility:
Name:
University Clinic of Tübingen
Address:
City:
Tübingen
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
NEC Bio Therapreutics
Phone:
0049 950499
Phone ext:
50
Email:
info@nec-bio.com
Start date:
October 15, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
NEC Bio B.V
Agency class:
Industry
Collaborator:
Agency:
NEC Bio Therapeutics
Agency class:
Industry
Source:
NEC Bio B.V
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06631092
