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 (NECVAX-NEO1-02-INT).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NEC Bio Therapeutics GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

7 Oct 2024 → ongoing

Decision date (initial)

2024-08-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511212-24-00

WHO UTN

U1111-1302-9616

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess safety and tolerability of NECVAX-NEO1, at two dose levels, in addition to PD-1/PD-L1 inhibitor therapy.

Secondary objectives 1

1. To assess the following in patients treated with NECVAX-NEO1, at two dose levels, in addition to PD-1/PD-L1 inhibitor therapy: • Antitumor activity, using molecular response as quantified by ctDNA assessment. • Clinical efficacy as determined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and iRECIST. • Overall survival (OS)

Conditions and MedDRA coding

Advanced solid tumors

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, State Medicines Control Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 PD-L1 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: a) 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 b) platelets ≥100 × 109/L c) 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 a) total bilirubin level ≤1.5 × ULN; patients with documented Gilbert disease are allowed if total bilirubin ≤3 × ULN b) 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.

Exclusion criteria 27

1. 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.
2. Medical and surgical history, and diseases: Other severe acute or chronic medical conditions (if there is one of the medical conditions at baseline, the patient should not be treated) including: a) immune colitis. b) inflammatory bowel disease. c) history of severe vomiting or diarrhea not having resolved to Grade 1 at Baseline. d) immune pneumonitis. e) pulmonary fibrosis. f) psychiatric conditions including recent (within the last year) or active suicidal ideation or behavior. g) 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.
3. Medical and surgical history, and diseases: History of small intestine resection surgery or other major gastrointestinal surgery.
4. Medical and surgical history, and diseases: Active infection requiring systemic therapy with antibiotics (at both Screening and Baseline).
5. Medical and surgical history, and diseases: Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome or multi-drug resistant gram-negative bacteria.
6. Medical and surgical history, and diseases: 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).
7. Medical and surgical history, and diseases: 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 months 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.
8. Medical and surgical history, and diseases: Known history of drug/substance abuse.
9. Prior and concomitant medication: Administration of live vaccines within 30 days prior to trial treatment.
10. Prior and concomitant medication: Treatment in any other clinical trial medication within 30 days before Screening.
11. Prior and concomitant medication: Any other condition or treatment that, in the opinion of the Investigator, might interfere with the trial.
12. Medical and surgical history, and diseases: Symptomatic brain metastasis.
13. Prior and concomitant medication: Current drug or substance abuse.
14. Prior and concomitant medication: Chronic concurrent therapy within 2 weeks before the trial treatment or expected therapy during the trial treatment period with: a) corticosteroids (except systemic corticosteroids up to 10 mg prednisolone or equivalent daily dose [oral, muscular, or intravenous]). b) immunosuppressive agents. c) antibiotics. d) 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, or cytokine therapy, except for erythropoietin.
15. Other: Inability to understand the Protocol requirements, instructions and trial-related restrictions, the nature, scope, and possible consequences of the trial.
16. Other: 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).
17. Other: Legal incapacity or limited legal capacity.
18. Other: Any condition which results in an undue risk for the patient during the trial participation according to the Investigator.
19. Medical and surgical history, and diseases: Any significant co-morbidity which, according to the Investigator’s judgement, makes patient compliance to trial conditions unlikely.
20. Medical and surgical history, and diseases: 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.
21. Medical and surgical history, and diseases: Prior organ transplantation, including allogeneic stem cell transplantation.
22. Medical and surgical history, and diseases: 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), which is acceptable.
23. Medical and surgical history, and diseases: 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)
24. Medical and surgical history, and diseases: 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).
25. Medical and surgical history, and diseases: 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.
26. Medical and surgical history, and diseases: Patients with increased anesthesiological risk (e.g. known or predicted difficult airway) if general anesthetic is required.
27. Medical and surgical history, and diseases: Patients with increased bleeding risk (e.g. coagulopathies) and patients on anticoagulants.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Reported adverse events (AEs) and serious adverse events (SAEs).
2. 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.

Secondary endpoints 5

1. Changes from baseline in circulating tumor DNA (ctDNA) assessments.
2. Clinical efficacy endpoints will be determined using RECIST 1.1 and iRECIST: • Objective response rate (ORR): Cohort 1: The proportion of patients having a best overall response (BOR) of complete response (CR) or partial response (PR) relative to assessment at the Screening visit. Cohort 2: The proportion of patients having a BOR of CR or PR relative to the baseline assessment (prior to administration of NECVAX-NEO1).
3. Progression-free-survival (PFS), defined as the time from first NECVAX-NEO1 administration to the first of progressive disease (PD) or death.
4. Time-to-Progression (TTP), defined as the time from first NECVAX-NEO1 administration to PD.
5. Additional clinical outcomes: • Overall survival (OS), defined as the time from first NECVAX-NEO1 administration to death.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NEC Bio Therapeutics GmbH

Sponsor organisation

NEC Bio Therapeutics GmbH

Address

Landteilstrasse 24, Lindenhof Lindenhof

City

Mannheim

Postcode

68163

Country

Germany

Scientific contact point

Organisation

NEC Bio Therapeutics GmbH

Contact name

Heinz Lubenau

Public contact point

Organisation

NEC Bio Therapeutics GmbH

Contact name

Heinz Lubenau

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications