Clinical Trials Register

Summary
EudraCT Number:	2019-002328-33
Sponsor's Protocol Code Number:	VB_C-02
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-09-12
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2019-002328-33

A.3

Full title of the trial

A Multi-Centre, Open-label Phase 2a Trial of the Combination of VB10.16 and Atezolizumab in Patients with Advanced or Recurrent, Non-resectable HPV16-Positive Cervical Cancer

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase 2 study for the Combination of VB10.16 and Atezolizumab in Patients with Advanced Cervical Cancer

A.4.1

Sponsor's protocol code number

VB_C-02

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	NYKODE THERAPEUTICS ASA
B.1.3.4	Country	Norway
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	NYKODE THERAPEUTICS ASA
B.4.2	Country	Norway
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Premier Research
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	Europaplatz 5
B.5.3.2	Town/ city	Darmstadt
B.5.3.3	Post code	64293
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4961512743058
B.5.5	Fax number	+4961518624600
B.5.6	E-mail	stefan.kretzschmar@premier-research.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	VB10.16
D.3.2	Product code	VB10.16
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VB10.16
D.3.9.2	Current sponsor code	VB10.16
D.3.9.3	Other descriptive name	VB10.16
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Yes
D.3.11.3.5.1	CAT classification and reference number	EMA/107652/2015
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Tecentriq
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Atezolizumab
D.3.2	Product code	Atezolizumab
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Atezolizumab
D.3.9.2	Current sponsor code	Atezolizumab
D.3.9.4	EV Substance Code	SUB178312
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced or recurrent non-resectable HPV16-positive cervical cancer, who failed or are not eligible for current standard of care

E.1.1.1

Medical condition in easily understood language

Advanced cervical cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10008229
E.1.2	Term	Cervical cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the safety/tolerability and clinical efficacy by overall response rate (ORR) of multiple doses of 3 mg VB10.16 immunotherapy in combination with atezolizumab

E.2.2

Secondary objectives of the trial

-To assess the immunogenicity of multiple doses of 3 mg VB10.16 immunotherapy in combination with 1200 mg atezolizumab
- To further assess efficacy of multiple doses of 3 mg VB10.16 immunotherapy in combination with 1200 mg atezolizumab in patients by PFS, duration of response (DOR), and OS

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Has persistent, recurrent, or metastatic non-resectable squamous cell carcinoma, adeno-squamous carcinoma, or adenocarcinoma of the cervix, who has failed or is not eligible for treatment with systemic chemotherapy, radiotherapy or other standard-of-care anticancer treatment.
2. Tumour must be HPV16 positive = as determined by central laboratory. Provision of an archival tumour tissue sample not older than 2 years or new biopsy for analysing HPV16 status is mandatory.
3. Must have a biopsy (archived or new) available for PD-L1 assessment at Screening. Provision of an archival tumour tissue sample not older
than 2 years or new biopsy for analysing PD-L1 status is mandatory.
4. Has measurable disease as assessed by the local site investigator/radiology as per RECIST 1.1.
5. Has recovered from the effects of surgery, radiation therapy, or chemoradiotherapy. At least 6 weeks must have elapsed from the last administration of chemoradiotherapy to Visit 1, and at least 3 weeks must have elapsed from the last administration of radiation therapy alone, and at least 4 weeks must have elapsed from the last dose of prior systemic anti-cancer therapy and from the time of any major surgical procedure before Visit 1.
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at Screening.
7. Is aged 18 years or older.
8. Has life expectancy of at least 6 months in the best judgement of the investigator.
9. Is willing and able to sign a written informed consent form.

E.4

Principal exclusion criteria

1.Patients with rapidly progressing disease who have experienced disease progression while on anticancer treatment within 3 months from the last dose of this treatment.
2. Has brain metastases (unless they have received prior treatment and are controlled and stable for at least 6 weeks before Visit 1) or leptomeningeal spread of disease.
3. Has positive serological test for:
-hepatitis C virus (HCV) and has not been treated; patients who are HCV-RNA negative would be eligible.
- hepatitis B virus (HBV) surface antigen (HBsAg); patients with positive HBV core antibody must have positive surface antibody and negative HBV viral load (HBV DNA) to be eligible.
- human immunodeficiency virus (HIV).
4. Has other concomitant or prior malignant disease, except for: a) adequately treated basal cell carcinoma or other non-melanomatous skin cancer, or low-grade urothelial cancer; b) other malignancies treated with curative intent, without disease recurrence and in complete remission with treatment completed 2 years or more before Screening study entry (time of providing consent).
5. Has an active, known or suspected autoimmune disease including, but not limited to, inflammatory bowel disease, systemic lupus erythematosus, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, vasculitis,glomerulonephritis and multiple sclerosis. Exceptions include: patients with vitiligo; autoimmune-related hypothyroidism on stable dose of hormone replacement; type 1 diabetes; mellitus on an insulin regimen; alopecia areata; psoriasis; eczema; and transient autoimmune manifestations of an acute infectious disease that
resolved upon treatment of the infectious agent (e.g., acute Lyme arthritis). Exceptions require discussion with the medical monitor.
6. Is receiving systemic immunosuppression including systemic steroids or the use of immunosuppressive agents (e.g., cyclosporine, azathioprine, methotrexate or tumour necrosis factor alfa [TNF-α] blockers) for any concurrent condition. All systemically administered corticosteroids must be discontinued >2 weeks prior to the first study vaccine administration.
7. Has known allergy to aminoglycosides (especially kanamycin) or any study treatment component.
8. Has history of toxic shock syndrome.
Please refer to section 8.2 of the protocol for the full criteria.

E.5 End points

E.5.1

Primary end point(s)

- Incidence and severity of adverse events (AEs)
-Overall response rate (ORR) defined as the proportion of patients in the analysis population who have complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at any time during the study

E.5.1.1

Timepoint(s) of evaluation of this end point

There will be continuous safety assessments (AEs) at screening and throughout the study according to the schedule of events. Tumour imaging by CT/MRI will occur at baseline, W9, W18, W27, W36 and W45 during the 48 weeks treatment period.

E.5.2

Secondary end point(s)

-Evaluate immunogenicity of VB10.16 in combination with atezolizumab by analysing HPV16 E6/E7-specific cellular immune responses during therapy
- Duration of response (DOR), defined as time from first RECIST 1.1 response (CR/PR) to the first date that disease progression is objectively documented or death from any cause
- Progression-free survival (PFS), defined as the time from first study treatment to the first documented disease progression according to RECIST 1.1 or death due to any cause, whichever occurs first
- Overall survival (OS) defined as time from first study treatment until death/EoS

E.5.2.1

Timepoint(s) of evaluation of this end point

Tumour imaging by CT/MRI will occur at baseline, W9, W18, W27, W36 and W45 during the 48 weeks treatment period.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will have access to further treatment with Atezolizumab after the end of the study (if clinically indicated).

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-04-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-11-24

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