An Open-label, Phase I/II Multicenter Clinical Trial of NECVAX-NEO1 in Addition to Anti-PD-1 or Anti-PD-L1 Monoclonal Antibody Therapy in Patients With Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- NECVAX-NEO1
- Conditions
- Solid Tumor
- Sponsor
- NEC Bio B.V
- Enrollment
- 20
- Locations
- 8
- Primary Endpoint
- Change from Baseline in Laboratory Parameters
- Status
- Active, not recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
Phase I/II multicenter, open-label, single-arm trial in patients to evaluate the safety and effect of NECVAX-NEO1 administered in combination with PD-1/PD-L1 mABs in patients with solid tumors. Patients with solid tumors who will be treated with approved standard of care (SoC) PD-1 or PD-L1 monoclonal antibody inhibitor therapy, and who after starting treatment with PD-1/PD-L1 inhibitor reached either Stable Disease (SD) or Partial Response (PR) (Cohort 1) or PD (Cohort 2) according to RECIST 1.1 and iRECIST assessed at the Baseline visit may be enrolled in the study
Detailed Description
Phase I/II multicenter, open-label, single-arm trial in patients to evaluate the safety and effect of NECVAX-NEO1 administered in combination with PD-1/PD-L1 mABs in patients with solid tumors. Patients with solid tumors who will be treated with approved standard of care (SoC) PD-1 or PD-L1 monoclonal antibody inhibitor therapy, and who after starting treatment with PD-1/PD-L1 inhibitor reached either Stable Disease (SD) or Partial Response (PR) (Cohort 1) or PD (Cohort 2) according to RECIST 1.1 and iRECIST assessed at the Baseline visit may be enrolled in the study. Personalised NECVAX-NEO1 is an oral, bacteria-based therapeutic vaccine that incorporates a sequence of patient-specific neoantigens selected by the NEC Immune Profiler. It is designed to stimulate the immune system of patients in order to induce a T-cell response that is able to specifically recognize and destroy tumor cells based on the patient's own neoantigens. NECVAX-NEO1 will be manufactured as a patient-specific Investigational Medicinal Product (IMP) for add-on therapy to the SoC PD-1/PD-L1 inhibitor therapy. For each patient, the trial will consist of: * Screening visit: To evaluate patients for inclusion in the trial. The patient signs the informed consent form (ICF), eligibility is confirmed, and a biopsy is taken to start manufacturing of the personalized NECVAX-NEO1. * Induction period. This is the SoC treatment period, during which treatment with PD-1/PD-L1 inhibitor therapy is started. This is approximately 8 to 12 weeks, depending on the type of PD-1/PD-L1 inhibitor used. The neoantigen selection and manufacturing of the personalized NECVAX-NEO1 takes place during the induction period. * Baseline visit. At this visit, when the personalized NECVAX-NEO1 treatment is available and the RECIST/iRECIST tumor assessment is performed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, eligibility will be re-confirmed, after which the patient will be assigned to either Cohort 1 (SD or PR according to RECIST 1.1) or Cohort 2 (PD according to RECIST 1.1). * Treatment period of up to 24 weeks which will mark the addition of new therapy to existing therapy, i.e., prime and booster administrations of NECVAX-NEO1 in addition to PD-1/PD-L1 inhibitor. * Post-treatment Follow-up period of 4 weeks, with an End of Treatment (EoT) visit at Week 28. * After the EoT (Week 28), a Long-Term Safety Monitoring Period, following the administration of a genetically modified organism, will occur 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).
- •Male or female patients.
- •Patients aged at least 18 years old at the time of ICF signature.
- •Patients with solid tumors with measurable disease according to RECIST 1.1, planned to be treated with a PD-1 or PDL1 inhibitor as first- or second-line standard of care therapy according to national/institutional guidelines:
- •Patients with tumor or metastasis accessible for guided needle biopsy or resection.
- •Patients with adequate bone marrow function at Screening, confirmed at Baseline, including:
- •absolute neutrophil count (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
- •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.
- •Symptomatic brain metastasis.
- •Any significant co-morbidity which, according to the Investigator's judgement, makes patient compliance to trial conditions unlikely.
- •Previous malignant disease (other than the tumor disease for this trial) within the last 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 2 years prior to Screening, and the patient is deemed to have been cured with no additional therapy required or anticipated to be required.
- •Prior organ transplantation, including allogeneic stem cell transplantation.
- •Congenital or any other immunodeficiency syndromes, or any active autoimmune disease that might deteriorate when receiving an immunostimulatory agent, except for:
- •patients with vitiligo, psoriasis, alopecia not requiring immunosuppressive treatment, are eligible.
- •administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation), which is acceptable.
- •History of uncontrolled intercurrent illness, including but not limited to uncontrolled hypertension (high blood pressure despite of combination therapy with diuretic/CCB/ACE or ARB).
Arms & Interventions
NECVAX-NEO1
Oral DNA Vaccine
Intervention: NECVAX-NEO1
Outcomes
Primary Outcomes
Change from Baseline in Laboratory Parameters
Time Frame: Up to week 24 plus 24 months
Laboratory Parameter Units
Serious Adverse Events
Time Frame: Up to week 24 plus 24 months
Serious 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)
Adverse Events
Time Frame: Up to week 24 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)
Change from Baseline in Electrocardiograms
Time Frame: Up to 24 weeks plus 24 months
ECG QT interval
Secondary Outcomes
- Antitumor activity(Up to 24 weeks)
- Objective Response Rate(Up to Week 24 plus 24 months)
- Progression free survival(Up to 24 weeks plus 24 months)
- Time to progression(Up to 24 weeks plus 24 months)
- Overall survival(Up to 24 weeks plus 24 months)