NECVAX-NEO1 for Triple-negative breast cancer

Inclusion criteria

• {"criterion_text":"- Patients able to understand and follow instructions during the trial."}
• {"criterion_text":"- Patients with adequate renal function at Screening, confirmed at Baseline, defined by eGFR ≥ 30 mL/min using 2021 CKD-EPI creatinine equation."}
• {"criterion_text":"- Patients must be able to undergo MRI or CT scan for tumor follow-up."}
• {"criterion_text":"- Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2."}
• {"criterion_text":"- Life expectancy of at least 12 months according to the Investigator’s judgement."}
• {"criterion_text":"- Patients able and willing to give written informed consent, signed and dated."}
• {"criterion_text":"- Female and male patients. Inclusion criteria to check only at Screening not needed to be checked again at Baseline"}
• {"criterion_text":"- Patients aged at least 18 years old at the time of ICF signature. Inclusion criteria to check only at Screening not needed to be checked again at Baseline"}
• {"criterion_text":"- cT2-4 N0 or any N-positive (stage II-III) triple-negative breast cancer patients diagnosed as candidates for first-line neoadjuvant anti-PD1 monoclonal antibody and chemotherapy epirubicin/cyclophosphamide and nab-paclitaxel therapy. Inclusion criteria to check only at Screening not needed to be checked again at Baseline"}
• {"criterion_text":"- Patients with tumor accessible for biopsy and surgery. Inclusion criteria to check only at Screening not needed to be checked again at Baseline"}
• {"criterion_text":"- Patients with adequate bone marrow function at Screening, confirmed at Baseline, including: a.\tANC ≥ 1.5 × 10^9/L; patients with documented benign cyclical neutropenia are eligible if white blood cell count is ≥ 1.5 × 10^9/L, with ANC ≥ 1.0 × 10^9/L, leukocytes ≥ 4.0 × 10^9/L, and lymphocytes ≥ 0.6 × 10^9/L; b.\tplatelets ≥ 100 × 10^9/L; patients with platelets ≥ 75 × 109/L (CTCAE v5.0 Grade 1) are eligible at Baseline; c.\themoglobin ≥ 9 g/dL (may have been transfused);"}
• {"criterion_text":"- International Normalized Ratio (INR) < 1.5×Upper Limit of Normal (ULN); patients treated with vitamin K antagonist are eligible if INR < 3."}
• {"criterion_text":"- Patients with adequate hepatic function at Screening, confirmed at Baseline, defined by a.\ttotal bilirubin level ≤1.5×ULN; patients with documented Gilbert disease are allowed if total bilirubin ≤3×ULN; b.\taspartate 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; patients with AST or ALT level >2.5xULN and <3xULN (CTCAE v5.0 Grade 1) are eligible at Baseline."}

Exclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients with a 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) etc. and uncontrolled diabetes (e.g., hemoglobin A1c ≥ 8%)."}
• {"criterion_text":"- Patients with a known prior hypersensitivity to the IMP 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)."}
• {"criterion_text":"- Patients with severe acute or chronic medical conditions, including: a.\tImmune colitis b.\tInflammatory bowel disease c.\tHistory of severe vomiting or diarrhea not having resolved to Grade 1 at Baseline d.\tImmune pneumonitis e.\tPulmonary fibrosis f.\tPsychiatric conditions including recent (within the last year) or active suicidal ideation or behavior. g.\tLaboratory 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Women who are pregnant or breastfeeding, or women of childbearing potential not willing to use acceptable methods of birth control."}
• {"criterion_text":"- Patients with a known history of drug/substance abuse."}
• {"criterion_text":"- Patients who received any live vaccines within 30 days prior to trial treatment."}
• {"criterion_text":"- Patients participating in any other clinical trial within 30 days before Screening."}
• {"criterion_text":"- Patients receiving any other treatment that, in the opinion of the Investigator, might interfere with the trial."}
• {"criterion_text":"- Patients receiving treatment with other experimental medicinal products in any other clinical trial medication within 30 days before Screening."}
• {"criterion_text":"- Patients with CTCAE v 5.0 not referred on the Inclusion Criteria #7, #8, #9 and #10 Grade 3 or higher at Screening or before Baseline not having resolved to Grade 1 at Baseline"}
• {"criterion_text":"- Patients receiving chronic concurrent therapy within two (2) weeks before the trial treatment or expected therapy during the trial treatment period with: a.\tCorticosteroids (except systemic corticosteroids up to 10 mg prednisolone or equivalent daily dose). b.\tImmunosuppressive agents. c.\tAntibiotics. d.\tAny other anticancer therapy or concurrent anticancer treatment except the neoadjuvant chemotherapy / anti-PD1 checkpoint inhibitor standard of care background therapy as per study protocol."}
• {"criterion_text":"- Patients unable to understand the protocol requirements, instructions and trial-related restrictions, the nature, scope, and possible consequences of the trial"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients with legal incapacity or limited legal capacity."}
• {"criterion_text":"- Patients with any condition which results in an undue risk for the patient during the trial participation according to the Investigator."}
• {"criterion_text":"- Patients with an active infection requiring systemic therapy with antibiotics (at both Screening and Baseline)."}
• {"criterion_text":"- Patients with a known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome or multi-drug resistant gram-negative bacteria."}
• {"criterion_text":"- Patients with CTCAE v 5.0 Grade 3 or higher not having resolved to Grade 1 within 6 weeks before Baseline."}
• {"criterion_text":"- Patients with any significant co-morbidity which, according to the Investigator’s judgement, makes patient compliance to trial conditions unlikely."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients who underwent prior organ transplantation, including allogeneic stem cell transplantation."}
• {"criterion_text":"- Patients with congenital or any other immunodeficiency syndromes, or any active autoimmune disease that might deteriorate when receiving an immunostimulatory agent, except for: a.\tPatients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment, are eligible. b.\tAdministration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation), is acceptable."}

Primary endpoints

• {"endpoint_text":"- Reported adverse events (AEs) and serious adverse events (SAEs)","definition_or_measurement_approach":"Collection and reporting of AEs and SAEs as safety outcomes (no further measurement approach specified in provided text)."}
• {"endpoint_text":"- Changes from Baseline in laboratory parameters (hematology, biochemistry, coagulation, and urinalysis), physical examinations, vital signs, and electrocardiograms (ECGs) during the Treatment and Follow-up periods.","definition_or_measurement_approach":"Assessment of changes from Baseline in laboratory parameters, physical examinations, vital signs and ECGs during Treatment and Follow-up periods (as written)."}

Secondary endpoints

• {"endpoint_text":"- Pathological complete response (pCR), defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current American Joint Committee on Cancer (AJCC) system)","definition_or_measurement_approach":"pCR defined as ypT0/Tis ypN0 assessed on H&E evaluation of resected breast specimen and sampled regional lymph nodes after neoadjuvant systemic therapy."}
• {"endpoint_text":"- Residual cancer burden (RCB) as a determinant of the extent of residual disease in post-surgery. Six variables are included in the formula. An RCB index value can also be calculated and involves the categorization into one of four RCB classes (RCB 0 or pCR, RCB I or near pCR, RCB II, RCB III)","definition_or_measurement_approach":"RCB calculated from six variables to yield RCB index and categorized into RCB classes (RCB 0/I/II/III) as described."}
• {"endpoint_text":"- Changes in ctDNA assessments compared to pre-treatment","definition_or_measurement_approach":"Molecular response assessed by circulating tumor DNA (ctDNA) comparisons to pre-treatment baseline (method as per protocol not detailed here)."}
• {"endpoint_text":"- Event-free survival (EFS), defined as the time from first dose of NECVAX-NEO1 to any of the following events: progression of disease that precludes surgery, local or distant recurrence, or death due to any cause up to the end of the safety follow-up at 24 months","definition_or_measurement_approach":"EFS measured from first NECVAX-NEO1 dose to progression precluding surgery, recurrence, or death, censored at end of safety follow-up at 24 months."}
• {"endpoint_text":"- Invasive disease-free survival (iDFS), defined as the time from first dose of NECVAX-NEO1 until local or distant recurrence or death due to any cause up to the end of the safety follow-up at 24 months","definition_or_measurement_approach":"iDFS measured from first NECVAX-NEO1 dose to local/distant recurrence or death, censored at 24 months safety follow-up."}
• {"endpoint_text":"- (Exploratory) Tumor tissue evaluations at Baseline, and at surgery (Week 12) compared to Screening, including effector T-cell infiltration, regulatory T-cells (Treg), Myeloid Derived Suppressor Cells (MDSC), PD-1, and mutational burden","definition_or_measurement_approach":"Exploratory comparisons of tumor tissue immune and molecular markers at Baseline vs surgery (Week 12) including enumerated cell populations and PD-1 and mutational burden."}
• {"endpoint_text":"- (Exploratory) Correlation between ctDNA and clinical efficacy/OS endpoints","definition_or_measurement_approach":"Exploratory analyses correlating ctDNA measures with clinical efficacy and overall survival endpoints (methods not detailed)."}
• {"endpoint_text":"- (Exploratory) Intestinal microbiome evaluation at Week 12, Week 24 and Week 36 (in case of optional prolongation) compared to Baseline","definition_or_measurement_approach":"Exploratory microbiome assessments at specified weeks compared to Baseline (methodology not provided)."}
• {"endpoint_text":"- (Exploratory) Clinical efficacy and OS endpoints, using pre-treatment as a reference date for changes, where applicable. Treatment response will also be assessed based on changes in tumor burden","definition_or_measurement_approach":"Exploratory clinical efficacy and OS endpoints referenced to pre-treatment; response assessed by changes in tumor burden (details per protocol)."}
• {"endpoint_text":"- (Exploratory) Overall survival (OS), defined as the time from first NECVAX-NEO1 administration to death","definition_or_measurement_approach":"OS measured from first NECVAX-NEO1 administration to death from any cause."}
• {"endpoint_text":"- (Exploratory) Clinical efficacy based on available RECIST 1.1 and iRECIST assessments: Objective response rate (ORR): proportion of patients having a best overall response (BOR) of complete response (CR) or partial response (PR) relative to assessment at the Screening visit","definition_or_measurement_approach":"ORR assessed by RECIST 1.1 and iRECIST comparing BOR to Screening assessment."}

Germany

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

603

Number Of Sites

3

Number Of Participants

12

Primary sponsor

Full Name

NEC Bio Therapeutics GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"Poland","full_name":"Kapadi Sp. z o.o.","duties_or_roles":"Sponsor duties codes: 1,10,11,12,15 (value for code 15: As per the Contract),2,5,6,7,8","organisation_type":"Pharmaceutical company"}