An Open-label, Phase I/II Multicenter Clinical Trial of NECVAX-NEO1 as add-on to First-line Neoadjuvant Anti-PD-1 Monoclonal Antibody Therapy in Patients With Triple-negative Breast Cancer
Overview
- Phase
- Phase 1
- Intervention
- Oral DNA Vaccine
- Conditions
- Triple Negative Breast Cancer
- Sponsor
- NEC Bio B.V
- Enrollment
- 12
- Locations
- 2
- Primary Endpoint
- Adverse Events
- Status
- Recruiting
- Last Updated
- 2 months ago
Overview
Brief 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 (cohort 1) or SoC carboplatin/paclitaxel and epirubicin/cyclophosphamide or doxorubicin/cyclophosphamide chemotherapy (cohort 2). 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 or SoC carboplatin/paclitaxel and epirubicin/cyclophosphamide or doxorubicin/cyclophosphamide chemotherapy. 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: Cohort 1 (n=8) * 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. Cohort 2 (n=4) * 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 paclitaxel 80 mg/m2 once weekly/carboplatin on an area under the concentration-time curve of 5 mg per milliliter per minute once weekly over 12 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 epirubicin 90 mg/m2/cyclophosphamide 600 mg/m2 or doxorubicin 60 mg/m2/cyclophosphamide 600 mg/m2 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients able to understand and follow instructions during the trial.
- •Patients able and willing to give written informed consent, signed and dated.
- •Female and male patients.
- •Patients aged at least 18 years old at the time of ICF signature.
- •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
- •Patients with tumor accessible for biopsy and surgery and showing at least 30% of tumoral cells on the biopsy.
- •Patients with adequate bone marrow function at Screening, confirmed at Baseline, including:
- •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;
- •platelets ≥ 100 × 109/L;
- •hemoglobin ≥ 9 g/dL (may have been transfused);
Exclusion Criteria
- •Medical and surgical history, and diseases
- •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.
- •Patients with CTCAE v 5.0 Grade 3 or higher not having resolved to Grade 1 within 6 weeks before Baseline.
- •Patients with any significant co-morbidity which, according to the Investigator's judgement, makes patient compliance to trial conditions unlikely.
- •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.
- •Patients who underwent prior organ transplantation, including allogeneic stem cell transplantation.
- •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.
- •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).
Arms & Interventions
NECVAX-NEO1
Personalised neoantigen-targeting oral DNA cancer vaccine
Intervention: Oral DNA Vaccine
Outcomes
Primary Outcomes
Adverse Events
Time Frame: Up to 36 weeks plus 24 months
AEs listed including system organ class, preferred term, severity, causality and other possibly relevant information. Frequency tables (including both patient and event counts) by System Organ Class (SOC) and preferred term (in number and percentage)
Serious Adverse Events
Time Frame: Up to 36 weeks plus 24 months
SAEs listed including system organ class, preferred term, severity, causality and other possibly relevant information. Frequency tables (including both patient and event counts) by System Organ Class (SOC) and preferred term (in number and percentage)
Change from Baseline in Laboratory Parameters
Time Frame: Up to 36 weeks plus 24 months
Laboratory defined units
Change from Baseline in Electrocardiograms
Time Frame: Up to 36 weeks plus 24 months
ECG QT interval
Secondary Outcomes
- Antitumor activity(Up to 36 weeks)
- Event-free survival(Up to 36 weeks plus 24 months)
- Invasive disease-free survival(Up to 36 weeks plus 24 months)
- Residual cancer burden(At week 12)
- Pathological complete response(At week 12)