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RBL001/RBL002 Phase I Clinical Trial (MERIT)

Primary Purpose

Melanoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RBL001/RBL002
Sponsored by
BioNTech RNA Pharmaceuticals GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Biontech, Biontech RNA Pharmaceuticals GmbH, Biontech RNA, MERIT, RNA, Immuno Therapy, RB_0001-01, Ribological, Melanoma, RBL001, RBL002, cancer vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Stage IIC, IIIA-C or unresectable stage IV of cutaneous melanoma (AJCC 2009 melanoma classification)
  • First line therapy for subjects not eligible or declining other first line therapies after all available treatment options have been transparently disclosed (to be documented!)
  • Antigen expression confirmed by RT-PCR analysis from FFPE
  • ≥ 18 years of age
  • Written informed consent (part I and part II)
  • ECOG performance status (PS) 0-1 or Karnofsky Index 70-100 %
  • Life expectancy > 3 months
  • WBC ≥ 3x109/L
  • Hemoglobin ≥ 10 g/dl
  • Platelet count ≥ 100,000/mm³
  • LDH level < 2.0 x ULN
  • Negative pregnancy test (measured by β-HCG) for females of childbearing age
  • Suitable lymph nodes for injection using ultrasound guidance

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Primary ocular melanoma
  • Presence of history (< 5 years) of a second malignancy other than squamous or basal cell carcinoma, non-active prostate cancer or cervical carcinoma in situ
  • Brain metastases
  • Known or symptomatic pleural effusions and/or ascites
  • Known hypersensitivity to the active substance or to any of the excipients
  • A serious local infection (e. g. cellulitis, abscess) or systemic infection (e. g. pneumonia, septicemia) which requires systemic antibiotic treatment within 2 weeks prior to the first dose of study medication
  • Acute or chronic active hepatitis B or C infection, EBV or CMV
  • Receipt of allogenic stem cell transplantation
  • Clinically relevant autoimmune disease
  • Systemic immune suppression:
  • HIV disease
  • Use of chronic oral or systemic steroid medication (topical or inhalational steroids are permitted) Other clinical relevant systemic immune suppression
  • Symptomatic congestive heart failure (NYHA 3 or 4)
  • Unstable angina pectoris
  • Radiotherapy, chemotherapy, major surgery, immunotherapy, vaccination, any other concurrent anticancer therapy or any investigational drug within 28 days before the first treatment of this study
  • Minor surgery within 14 days before the first treatment of this study
  • Treatment with Ipilimumab within 84 days before the first treatment of this study
  • Fertile males and females who are unwilling to employ adequate means of contraception (e. g. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches or intrauterine device) during study treatment and 28 days after the last dose of study treatment
  • Presence of a serious concurrent illness or other condition (e. g. psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the protocol

Sites / Locations

  • Medizinische Universität Wien, Abteilung für Dermatologie
  • Medizinische Fakultät der Universität Duisburg-Essen
  • Universtitätsmedizin der Johannes-Gutenberg Universtität
  • Universitätsklinik Mannheim

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RBL001/RBL002 intranodal administration

Arm Description

All participants will be treated with RBL001/RBL002 after allocation to one of the four escalating dose cohorts: Cohort-1 50 µg RBL001 and 50 µg RBL002 Cohort-2 100 µg RBL001 and 100 µg RBL002 Cohort-3 300 µg RBL001 and 300 µg RBL002 Cohort-4 600 µg RBL001 and 600 µg RBL002

Outcomes

Primary Outcome Measures

Number of adverse events
Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities

Secondary Outcome Measures

Determination of antitumoral immune responses
Cellular immune responses, cytokines, AB responses, serum biomarkers, and further immunological parameters will be determined once or repeatedly in the course of treatment. In the latter case changes from baseline will be tabulated.
Clinical Monitoring of Tumor Lesions
Tumor lesion status as determined by CT or MRI results evaluated by irRC and RECIST.

Full Information

First Posted
September 10, 2012
Last Updated
January 14, 2020
Sponsor
BioNTech RNA Pharmaceuticals GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT01684241
Brief Title
RBL001/RBL002 Phase I Clinical Trial
Acronym
MERIT
Official Title
Clinical First-in-human Dose Escalation Study Evaluating the Safety and Tolerability of Intranodal Administration of an RNA-based Cancer Vaccine Targeting Two Tumor-associated Antigens in Patients With Advanced Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioNTech RNA Pharmaceuticals GmbH

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Clinical first-in-human dose escalation study evaluating the safety and tolerability of intranodal administration of an RNA-based cancer vaccine targeting two tumor-associated antigens in patients with advanced melanoma
Detailed Description
RBL001/RBL002 are naked ribonucleic acid (RNA) based recombinant vaccines that were optimized to induce antigen specific CD8+ and CD4+ T cell responses against malignant melanoma target antigens. The Targeted antigens are well characterized antigens in melanoma that have been previously utilized with excellent safety and proven immunogenicity as vaccine targets in a number of independent clinical trials. The overall rationale of the study is to determine safety of the novel RNA based vaccine approach and determine vaccine target antigen directed immune responses as early biomarkers for clinical mode of action. The RBL001/RBL002 vaccine is expected to lead to several effects contributing to its immunological (therapeutic) effect. First, ultrasound guided administration of naked RNA drug product into lymph nodes is expected to result in rapid uptake of naked RNA by lymph node resident professional antigen-presenting cells (APCs). Incorporated RNA is known to translocate to the cytoplasm leading to its translation by the host ribosome complex into the respective protein antigens. The recombinant vaccine is optimized for immunogenicity and enables presentation of diverse antigenic epitopes on both HLA-class I as well as HLA-class II molecules. Consecutively, antigen-specific CD8+ and CD4+ T cell responses will be triggered by HLA-peptide complexes on the surface of antigen presenting cells. In addition, RNA administration will also lead to transient activation (change of surface marker expression and cytokine secretion) of APCs in the targeted lymph nodes particularly via signaling of TLR 7 and 8 leading to an adjuvant effect, supporting the induction of target-specific T cell responses with systemic anti-tumor activity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Biontech, Biontech RNA Pharmaceuticals GmbH, Biontech RNA, MERIT, RNA, Immuno Therapy, RB_0001-01, Ribological, Melanoma, RBL001, RBL002, cancer vaccine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RBL001/RBL002 intranodal administration
Arm Type
Experimental
Arm Description
All participants will be treated with RBL001/RBL002 after allocation to one of the four escalating dose cohorts: Cohort-1 50 µg RBL001 and 50 µg RBL002 Cohort-2 100 µg RBL001 and 100 µg RBL002 Cohort-3 300 µg RBL001 and 300 µg RBL002 Cohort-4 600 µg RBL001 and 600 µg RBL002
Intervention Type
Biological
Intervention Name(s)
RBL001/RBL002
Other Intervention Name(s)
cancer vaccine
Intervention Description
Each participant will receive 8 repeated intranodal administrations of RBL001 and RBL002 during a time frame of 43 to 51 days.
Primary Outcome Measure Information:
Title
Number of adverse events
Description
Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Determination of antitumoral immune responses
Description
Cellular immune responses, cytokines, AB responses, serum biomarkers, and further immunological parameters will be determined once or repeatedly in the course of treatment. In the latter case changes from baseline will be tabulated.
Time Frame
90 days
Title
Clinical Monitoring of Tumor Lesions
Description
Tumor lesion status as determined by CT or MRI results evaluated by irRC and RECIST.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Stage IIC, IIIA-C or unresectable stage IV of cutaneous melanoma (AJCC 2009 melanoma classification) First line therapy for subjects not eligible or declining other first line therapies after all available treatment options have been transparently disclosed (to be documented!) Antigen expression confirmed by RT-PCR analysis from FFPE ≥ 18 years of age Written informed consent (part I and part II) ECOG performance status (PS) 0-1 or Karnofsky Index 70-100 % Life expectancy > 3 months WBC ≥ 3x109/L Hemoglobin ≥ 10 g/dl Platelet count ≥ 100,000/mm³ LDH level < 2.0 x ULN Negative pregnancy test (measured by β-HCG) for females of childbearing age Suitable lymph nodes for injection using ultrasound guidance Exclusion Criteria: Pregnancy or breastfeeding Primary ocular melanoma Presence of history (< 5 years) of a second malignancy other than squamous or basal cell carcinoma, non-active prostate cancer or cervical carcinoma in situ Brain metastases Known or symptomatic pleural effusions and/or ascites Known hypersensitivity to the active substance or to any of the excipients A serious local infection (e. g. cellulitis, abscess) or systemic infection (e. g. pneumonia, septicemia) which requires systemic antibiotic treatment within 2 weeks prior to the first dose of study medication Acute or chronic active hepatitis B or C infection, EBV or CMV Receipt of allogenic stem cell transplantation Clinically relevant autoimmune disease Systemic immune suppression: HIV disease Use of chronic oral or systemic steroid medication (topical or inhalational steroids are permitted) Other clinical relevant systemic immune suppression Symptomatic congestive heart failure (NYHA 3 or 4) Unstable angina pectoris Radiotherapy, chemotherapy, major surgery, immunotherapy, vaccination, any other concurrent anticancer therapy or any investigational drug within 28 days before the first treatment of this study Minor surgery within 14 days before the first treatment of this study Treatment with Ipilimumab within 84 days before the first treatment of this study Fertile males and females who are unwilling to employ adequate means of contraception (e. g. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches or intrauterine device) during study treatment and 28 days after the last dose of study treatment Presence of a serious concurrent illness or other condition (e. g. psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ugur Sahin, Prof. Dr.
Organizational Affiliation
Ribological GmbH
Official's Role
Study Director
Facility Information:
Facility Name
Medizinische Universität Wien, Abteilung für Dermatologie
City
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Medizinische Fakultät der Universität Duisburg-Essen
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Universtitätsmedizin der Johannes-Gutenberg Universtität
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Universitätsklinik Mannheim
City
Mannheim
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

RBL001/RBL002 Phase I Clinical Trial

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