Trial Title:
Personalised Neoantigen-targeting Cancer Vaccine NECVAX-NEO1 in Anti-PD-1/PD-L1 Therapy in Patients With Solid Tumors
NCT ID:
NCT06631079
Condition:
Solid Tumor
Conditions: Official terms:
Neoplasms
Vaccines
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:
NECVAX-NEO1
Description:
Bacteria-based orally administered personalised neoantigen-targeting cancer vaccine
Arm group label:
NECVAX-NEO1
Other name:
Personalised neoantigen-targeting oral DNA cancer vaccine
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.
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. Male or female patients.
4. Patients aged at least 18 years old at the time of ICF signature.
5. 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:
6. Patients with tumor or metastasis accessible for guided needle biopsy or resection.
7. Patients with adequate bone marrow function at Screening, confirmed at Baseline,
including:
1. 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;
2. platelets ≥ 100 × 109/L;
3. hemoglobin ≥9 g/dL (may have been transfused);
8. 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).
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 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).
11. Patients must be able to undergo MRI or CT scan for tumor follow-up.
12. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
13. 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
1. 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. Symptomatic brain metastasis.
3. Any significant co-morbidity which, according to the Investigator's judgement, makes
patient compliance to trial conditions unlikely.
4. 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.
5. Prior organ transplantation, including allogeneic stem cell transplantation.
6. Congenital or any other immunodeficiency syndromes, or any active autoimmune disease
that might deteriorate when receiving an immunostimulatory agent, except for:
1. patients with vitiligo, psoriasis, alopecia not requiring immunosuppressive
treatment, are eligible.
2. administration of steroids through a route known to result in a minimal
systemic exposure (topical, intranasal, intro-ocular, or inhalation), which is
acceptable.
7. 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).
8. 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).
9. 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.
10. Other severe acute or chronic medical conditions (if there is one of the medical
conditions at baseline, the patient should not be treated), 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.
11. History of small intestine resection surgery or other major gastrointestinal surgery
12. Active infection requiring systemic therapy with antibiotics (at both Screening and
Baseline).
13. Known history of human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome or multi-drug resistant gram-negative bacteria.
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. 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).
17. 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
18. Known history of drug/substance abuse. Prior and concomitant medication
19. Live vaccines within 30 days prior to trial treatment.
20. Treatment in any other clinical trial medication within 30 days, before Screening.
21. Any other condition or treatment that, in the opinion of the Investigator, might
interfere with the trial.
22. Current drug or substance abuse.
23. Chronic concurrent therapy within 2 weeks before the trial treatment or expected
during the trial treatment period with:
1. corticosteroids (except systemic corticosteroids up to 10 mg prednisolone or
equivalent daily dose [oral, intramuscular, or intravenous]).
2. immunosuppressive agents.
3. antibiotics.
4. any other anticancer therapy or concurrent anticancer treatment (except for
other checkpoint inhibitors in combination with the anti-PD-1 or anti-PD-L1
monoclonal antibody), for example, cytoreductive therapy, radiotherapy with the
exception of palliative short course, limited field (i.e., ≤10 fractions and
≤30% bone marrow involvement or per institutional standard) radiotherapy, which
may be administered during the trial. However, IMP dosing must be suspended at
least 14 days prior to the start of radiotherapy and must not be resumed until
at least 14 days after the last radiotherapy fraction, cytokine therapy, except
for erythropoietin.
Other
24. Inability to understand the Protocol requirements, instructions and trial-related
restrictions, the nature, scope, and possible consequences of the trial.
25. 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).
26. Legal incapacity or limited legal capacity.
27. 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:
Fundacion Jimenez Diaz
Address:
City:
Madrid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Heinz Lubenau, Dr
Phone:
+49 621 950499 50
Email:
info@nec-bio.com
Facility:
Name:
CHUS Santiago de Compostela
Address:
City:
Santiago De Compostela
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Heinz Lubenau, Dr
Contact backup:
Phone:
+49 621 950 49950
Email:
info@nec-bio.com
Start date:
October 7, 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/NCT06631079
