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About
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
Full 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:
Enrollment
Sex
Ages
Volunteers
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:
International Normalized Ratio (INR) <1.5 × the upper limit of normal (ULN); patients treated with vitamin K antagonist are eligible if INR <3 (at Screening and confirmed at Baseline).
Patients with adequate hepatic function at Screening, confirmed at Baseline, defined by
Patients with adequate renal function at Screening, confirmed at Baseline, defined by estimated glomerular filtration rate (eGFR) ≥ 30 mL/min using 2021 CKD-EPI creatinine equation (eGFR =142*min(standardized Scr/K, 1)α*max(standardized Scr/K, 1)-1.200 *0.9938Age *1.012 [if female] where K = 0.7 [females] or 0.9 [males], α = -0.241 [females] or -0.302 [males], min = indicates the minimum of Scr/K or 1, and max = indicates the maximum of Scr/K or 1).
Patients must be able to undergo MRI or CT scan for tumor follow-up.
Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
Life expectancy of at least 6 months at the time of ICF signature, according to the Investigator's judgement at the time of ICF signature.
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:
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).
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).
Persisting toxicity related to prior therapy (NCI CTCAE v5.0 Grade >1); however, alopecia, sensory neuropathy Grade ≤2, or other Grade ≤2 AEs not constituting a safety risk based on Investigator's judgement are acceptable.
Other severe acute or chronic medical conditions (if there is one of the medical conditions at baseline, the patient should not be treated), including
History of small intestine resection surgery or other major gastrointestinal surgery
Active infection requiring systemic therapy with antibiotics (at both Screening and Baseline).
Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome or multi-drug resistant gram-negative bacteria.
Patients with increased anesthesiological risk (e.g. known or predicted difficult airway) if general anesthetic is required.
Patients with increased bleeding risk (e.g. coagulopathies) and patients on anticoagulants.
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).
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 moths of amenorrhea and at least 50 years of age) not willing to use highly effective methods of birth control up to 6 months after the last dose of IMP. Males of child-bearing potential not willing to use a highly effective method of birth control to avoid pregnancy with any partner during the study and until 90 days after the last dose of IMP
Known history of drug/substance abuse. Prior and concomitant medication
Live vaccines within 30 days prior to trial treatment.
Treatment in any other clinical trial medication within 30 days, before Screening.
Any other condition or treatment that, in the opinion of the Investigator, might interfere with the trial.
Current drug or substance abuse.
Chronic concurrent therapy within 2 weeks before the trial treatment or expected during the trial treatment period with:
Other
Inability to understand the Protocol requirements, instructions and trial-related restrictions, the nature, scope, and possible consequences of the trial.
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).
Legal incapacity or limited legal capacity.
Any condition which results in an undue risk for the patient during the trial participation according to the Investigator.
Primary purpose
Allocation
Interventional model
Masking
20 participants in 1 patient group
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Central trial contact
Heinz Lubenau, Dr
Data sourced from clinicaltrials.gov
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