Trial of RNActive®-Derived Cancer Vaccine and Local Radiation in in Stage IV Non Small Cell Lung Cancer (NSCLC)

NCT ID: NCT01915524

Last Updated: 2016-08-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2016-07-31

Brief Summary

The purpose of this study is to determine whether the new RNActive derived lung cancer vaccine CV9202 in combination with local radiation therapy is safe, tolerable and immunogenic for the consolidation and maintenance treatment of stage IV non small cell lung cancer (NSCLC) after first-line chemotherapy or therapy with an EGFR tyrosine kinase inhibitor.

Detailed Description

The Phase Ib study is the first clinical study with the new lung cancer vaccine CV9202. The vaccine is composed of 6 RNActive compounts, each encoding for a different antigen which is overexpressed in NSCLC compared to healthy tissue.

In order to enhance the immunogenic effect of the cancer vaccine, the study treatment will include local radiation (4 x 5 Gy), which is a well-established palliative radiation regimen that can be safely applied to metastatic lesions in the lung, bone, and soft tissue, and is well tolerated.

Patients will be enrolled into 3 strata based on histologic and molecular subtypes as follows:

Stratum 1: Patients with metastatic stage IV NSCLC and non-squamous histology, without activating epidermal growth factor receptor (EGFR) mutations, who have achieved partial response (PR) or stable disease (SD) after at least 4 cycles of platinum- and pemetrexed-based first-line chemotherapy, and an indication for maintenance therapy with pemetrexed.

Stratum 2: Patients with stage IV NSCLC and squamous cell histology, who achieved PR or SD after at least 4 cycles of platinum-based and non-platinum compound first-line chemotherapy.

Stratum 3: Patients with stage IV NSCLC and non-squamous histology, harboring an activating EGFR mutation, who have achieved PR after up to 6 months or SD after 3 - 6 months of treatment with an EGFR TKI.

In each patient, the vaccine will be administered until progression and the need to start a subsequent systemic second-line treatment, or occurrence of unacceptable toxicity requiring treatment discontinuation, whichever comes first.

Conditions

Non-Small Cell Lung Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CV9202 and local radiation

CV9202 consisting of 6 RNActive-derived molecules coding for 6 different NSCLC associated antigens.

local radiation (4x5 Gy)

Group Type: EXPERIMENTAL

CV9202

Intervention Type: BIOLOGICAL

Intradermal injection of CV9202

local radiation

Intervention Type: RADIATION

Radiotherapy will be administered in 4 daily fractions of 5 GY each to be administered within one week

Interventions

CV9202

Intradermal injection of CV9202

Intervention Type: BIOLOGICAL

local radiation

Radiotherapy will be administered in 4 daily fractions of 5 GY each to be administered within one week

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. Patients >= 18 years of age with histologically or cytologically-confirmed stage IV NSCLC, and a confirmed EGFR mutation status in case of non-squamous cell histology

• Stratum 1: Non-squamous NSCLC without activating EGFR mutation
• Stratum 2: Squamous NSCLC
• Stratum 3: Non-squamous NSCLC harboring an activating EGFR mutation

2. PR or SD according to RECIST Version 1.1 after first-line therapy which should have consisted of:

• Stratum 1: PR or SD after cisplatin or carboplatin and pemetrexed treatment (at least 4 cycles)
• Stratum 2: PR or SD after cisplatin or carboplatin and a non-platinum compound treatment (at least 4 cycles)
• Stratum 3: PR after up to 6 months or SD after at least 3 and up to 6 months of gefitinib or erlotinib treatment

3. For patients in stratum 1, maintenance therapy with pemetrexed should be indicated as to the investigator's opinion

4. Presence of at least one tumor lesion that is eligible for radiation with 4 x 5 GY, and at least one additional measurable tumor lesion according to RECIST Version 1.1.

Tumor lesions eligible for radiation are:

• Bone metastases
• Lymph nodes in the paraclavicular, axillary or cervical regions
• Skin or subcutaneous metastases
• For patients in strata 1 and 2 only: Thoracic lesions (centrally located lung tumor, lymph nodes in the lung hilus or mediastinum)

5. Performance Status: Eastern Cooperative Oncology Group (ECOG) 0 to 1

Exclusion Criteria

1. Previous active immunotherapy for NSCLC (including vaccination, therapy with anti-CTLA4 antibodies)

2. Estimated life expectancy ≤ 3 months

3. Need for immunosuppressive treatment including daily systemic steroid doses of ≥ 10 mg prednisone equivalent per day

4. Active skin disease (e.g. atopic dermatitis) in the areas for vaccine injection (upper arms or thighs) not allowing intradermal injections into areas of healthy skin

5. Concurrent or planned major surgery

6. Prior splenectomy or prior allogeneic bone marrow transplantation

7. History of pneumonitis

8. Documented history or active autoimmune disorders with the exception of vitiligo, diabetes mellitus type 1 or autoimmune thyroiditis requiring hormone replacement only

9. Primary or secondary immune deficiency

10. Allergies to any components of the study drug including allergy to protamine hydrochloride (e.g. allergy to protamine-containing insulin) or fish allergy

11. Seropositive for HIV, HBV, HCV or any other infection requiring anti-infection therapy

12. For patients in stratum 3: persisting >= grade 3 skin rash at time of enrollment

13. Known brain metastases with the exception of stable metastases being treated with stereotactic radiation or surgery)

**Local German Amendment: 13. Brain metastases (symptomatic or asymptomatic) or leptomeningeal involvement

14. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug (e.g. unstable diabetes mellitus, vena-cava-syndrome, uncontrolled pleural effusion, pericardial effusion, symptomatic congestive heart failure (New York Heart Association 3 or 4), unstable angina pectoris/myocardial infarction within the previous 6 months, significant cardiac arrhythmia, history of stroke or transient ischemic attack within the previous 6 months, severe hypertension according to WHO criteria, and uncontrolled systolic blood pressure ≥ 180 mmHg at the time of enrollment

15. For patients planned to undergo radiation of thoracic lesions: inadequate lung function dependent on the intended tumor volume and location to be irradiated (to be assessed by the radio oncologist)

16. History of encephalitis or multiple sclerosis

17. Active inflammatory conditions such as inflammatory bowel disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CureVac

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alfred Zippelius, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Basel, Clinic for Medical Oncology

Locations

Innsbruck Medical University, Department of Internal Medicine V (Hematology and Oncology)

Innsbruck, , Austria

HELIOS Klinikum Emil von Behring GmbH

Berlin, , Germany

Augusta-Kranken-Anstalt gGmbH

Bochum, , Germany

Kliniken der Stadt Köln gGmbH

Cologne, , Germany

Klinikum Esslingen GmbH

Esslingen am Neckar, , Germany

University Hospital Frankfurt, Department of Medicine II: Hematology/Oncology

Frankfurt, , Germany

Thoraxklinik-Heidelberg gGmbH

Heidelberg, , Germany

University Medical Center Mainz, III. Medical Clinic and Policlinic

Mainz, , Germany

Pius-Hospital Oldenburg

Oldenburg, , Germany

University Hospital Basel, Clinic for Oncology

Basel, , Switzerland

Kantonsspital Graubünden

Chur, , Switzerland

Kantonspital St. Gallen

Sankt Gallen, , Switzerland

Kantonspital Winterthur, Oncology

Winterthur, , Switzerland

Countries

Austria; Germany; Switzerland

References

Papachristofilou A, Hipp MM, Klinkhardt U, Fruh M, Sebastian M, Weiss C, Pless M, Cathomas R, Hilbe W, Pall G, Wehler T, Alt J, Bischoff H, Geissler M, Griesinger F, Kallen KJ, Fotin-Mleczek M, Schroder A, Scheel B, Muth A, Seibel T, Stosnach C, Doener F, Hong HS, Koch SD, Gnad-Vogt U, Zippelius A. Phase Ib evaluation of a self-adjuvanted protamine formulated mRNA-based active cancer immunotherapy, BI1361849 (CV9202), combined with local radiation treatment in patients with stage IV non-small cell lung cancer. J Immunother Cancer. 2019 Feb 8;7(1):38. doi: 10.1186/s40425-019-0520-5.

Reference Type: DERIVED

PMID: 30736848 (View on PubMed)

Sebastian M, Papachristofilou A, Weiss C, Fruh M, Cathomas R, Hilbe W, Wehler T, Rippin G, Koch SD, Scheel B, Fotin-Mleczek M, Heidenreich R, Kallen KJ, Gnad-Vogt U, Zippelius A. Phase Ib study evaluating a self-adjuvanted mRNA cancer vaccine (RNActive(R)) combined with local radiation as consolidation and maintenance treatment for patients with stage IV non-small cell lung cancer. BMC Cancer. 2014 Oct 6;14:748. doi: 10.1186/1471-2407-14-748.

Reference Type: DERIVED

PMID: 25288198 (View on PubMed)

Related Links

http://www.curevac.de

Click here for more information about CureVac

Other Identifiers

CV-9202-006

Identifier Type: -

Identifier Source: org_study_id