RNA-Immunotherapy of IVAC_W_bre1_uID and IVAC_M_uID

NCT02316457 | Completed Phase 1 DMC

• 1 other identifier: BN_0002-01
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 4

Brief Summary

The Mutanome Engineered RNA Immuno-Therapy (MERIT) study introduced a novel concept for Individualized Cancer Immunotherapy (IVAC®) to treat each patient with the relevant and immunogenic RNA vaccines for a given patient's tumor. The TNBC-MERIT trial used two complementary strategies, the WAREHOUSE and the IVAC® MUTANOME concept, resulting in two custom-made IVAC® investigational medicinal products (IMPs) (IVAC\_W\_bre1\_uID and IVAC\_M\_uID) for each individual patient.

Conditions

Breast Cancer (Triple Negative Breast Cancer (TNBC))

Keywords

TNBC; Breast Cancer; Warehouse; Mutanome; RNA; Vaccine

Outcome Measures

Primary Outcomes (2)

• Number of Adverse Events as a Measure of Safety and Tolerability of IVAC_W_bre1_uID

  Assessment of AEs

  day 120

• Number of Adverse Events as a Measure of Safety and Tolerability of IVAC_W_bre1_uID plus IVAC_M_uID

  Assessment of AEs, End of treatment visit is depending on treatment schedule

  up to day 246

Secondary Outcomes (2)

• Change of induced T-cell responses for IVAC_W_bre_uID change from Visit 1 to V10

  up to 78 days

• Change of induced T-cell responses for IVAC_M_uID change from Visit 18 to Follow-up Visit

  up to 78 days

Study Arms (3)

ARM1 IVAC_W_bre1_uID

EXPERIMENTAL

Patients enrolled in ARM1 will receive a treatment with four RNAs. This includes two to three variant RNAs selected from the WAREHOUSE plus p53 RNA. The selection process of RNAs from the warehouse is based on RT-PCR-based profiling of RNA extracted from patient tumor sample specimens, pre-defined cut-offs and algorithms to select the three relevant RNAs for a given patient.

Biological: IVAC_W_bre1_uID

ARM2 IVAC_W_bre1_uID/IVAC_M_uID

EXPERIMENTAL

Patients enrolled in ARM2 will optionally receive the WAREHOUSE treatment as described above followed by the personalized IVAC® MUTANOME immunotherapy. The mutation selection process constitutes a multi-step process including identification of somatic mutations by NGS, mutation confirmation and prioritization, selection, and on demand manufacturing.

Biological: IVAC_W_bre1_uID/IVAC_M_uID

ARM3 IVAC_W_bre1_uID + RBLTet.1

EXPERIMENTAL

Patients enrolled in ARM3 will receive a treatment with four RNAs. This includes two to three variant RNAs selected from the WAREHOUSE plus p53 RNA. The selection process of RNAs from the warehouse is based on RT-PCR-based profiling of RNA extracted from patient tumor sample specimens, pre-defined cut-offs and algorithms to select the three relevant RNAs for a given patient. RBLTet.1 RNA will be added to each RNA applied.

Biological: IVAC_W_bre1_uID

Interventions

IVAC_W_bre1_uID BIOLOGICAL

vaccination

ARM1 IVAC_W_bre1_uID; ARM3 IVAC_W_bre1_uID + RBLTet.1

IVAC_W_bre1_uID/IVAC_M_uID BIOLOGICAL

vaccination

ARM2 IVAC_W_bre1_uID/IVAC_M_uID

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed invasive adenocarcinoma triple negative breast cancer (TNBC), pT1cN0M0 - anyTanyNM0 confirmed by physical examination or imaging
• Triple negative breast cancer was defined as:
• HER2 negative
• IHC 0-1+
• IHC 2+ and FISH negative (ratio \< 2.0 or \< 4 gene copies / cell, as per new ASCO guideline)
• ER and PR negative confirmed\< 1%
• For patients with surgery of primary tumor followed by adjuvant chemotherapy, treatment with IVAC\_W\_bre1\_uID was initiated after completion of the adjuvant chemotherapy. The adjuvant chemotherapy should contain anthracyclines and taxanes - except for patients with contraindications for treatment with one or both substances.
• For patients with neoadjuvant chemotherapy according to local standard followed by surgery of primary tumor, treatment with IVAC\_W\_bre1\_uID was initiated after the surgery. The neoadjuvant chemotherapy should contain anthracyclines and taxanes - except for patients with contraindications for treatment with one or both substances.
• Patients with planned radiotherapy (as per local policy) were eligible and should be irradiated in parallel to the vaccination cycles
• Patients after completion of standard of care therapy e. g. surgery and/or chemotherapy and/or radiotherapy (as per local policy) were eligible at the discretion of the investigator after no clinical sings of recurrence and/or metastasis, if the treatment with IVAC\_W\_bre1\_uID starts within one year after completion of the radiotherapy.
• Adequate organ function (hematopoietic, hepatic and renal function):
• Hemoglobin ≥ 9 g/dl
• ANC ≥ 1500/µl
• Platelet count ≥ 100,000/mm³
• ALT/AST \<2 x ULN

You may not qualify if:

• Patients with stage pT1a,bN0M0 and anyTanyNM1disease were excluded
• Patients with recurrence of breast cancer prior to the start of study treatment with IVAC\_W\_bre1\_uID
• Any serious local infection (e. g. cellulitis, abscess) or systemic infection (e. g. pneumonia, septicemia, viral or fungal infection) which requires systemic treatment with antibiotics or corticoid therapy within two weeks prior to the first dose of study medication
• Previous splenectomy
• Concurrence of a second malignancy other than squamous or basal cell carcinoma or cervical carcinoma in situ within 5 years prior to the start of study treatment
• Known hypersensitivity to the active substance or to any of the excipients
• Prior solid organ transplantation or hematopoietic stem cell transplantation
• Positive test for acute Hepatitis A, acute or chronic active Hepatitis B or C infection
• Clinically relevant active autoimmune disease
• Systemic immune suppression:
• HIV disease
• Use of chronic oral or systemic steroid medication (topical or inhalational steroids are permitted)
• Other clinically relevant systemic immune suppression
• Symptomatic congestive heart failure (NYHA 3 or 4)
• Unstable angina pectoris

Sponsors & Collaborators

• BioNTech SE: lead
• Seventh Framework Programme: collaborator

Study Sites (4)

Johannes Gutenberg University

Mainz, RLP, 55131, Germany

Location

National Center for Tumor Diseases (NCT)

Heidelberg, 69120, Germany

Location

Dr. Horst Schmidt-Kliniken Wiesbaden

Wiesbaden, 65199, Germany

Location

Uppsala University Hospital

Uppsala, 75185, Sweden

Location

Related Links

• BioNTech SE

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2014
• First Posted: December 15, 2014
• Study Start: October 1, 2016
• Primary Completion: May 13, 2020
• Study Completion: May 17, 2023
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); DE (3)