Investigating the Combination of VB10.16 and Atezolizumab in Patients With HPV 16-positive Cervical Cancer

Phase 2

Completed

• Conditions: Cervical Cancer; Cervix Cancer
• Interventions: Biological: VB10.16; Biological: Atezolizumab

• Registration Number: NCT04405349
• Lead Sponsor: Nykode Therapeutics ASA

Brief Summary

This phase IIa study is designed to evaluate the safety and efficacy of multiple dosing with VB10.16 immunotherapy in combination with atezolizumab in patients with advanced or recurrent non-resectable HPV16-positive cervical cancer, who failed or are not eligible for current standard of care.

Detailed Description

Patients will receive up to 11 intramuscular (i.m.) vaccinations of VB10.16, for up to 48 weeks from first vaccination. Patients will receive 5 vaccinations of 3 mg VB10.16 during the first 12 weeks, followed by vaccination every 6 weeks for up to 48 weeks from first immunisation (total of 11 vaccinations). Patients will receive up to 17 infusions of atezolizumab for up to 48 weeks from first treatment. Atezolizumab (1200 mg) will be administered as an intravenous (i.v.) infusion every 3 weeks. A follow-up period of up to 12 months will follow the 48 week treatment period.

Response to the VB10.16 and atezolizumab combination will be assessed by computed tomography (CT)/magnetic resonance imaging (MRI) at every 9 weeks throughout the treatment period according to the RECIST 1.1 criteria.

Study Timeline

• Study First Submitted: 2020-04-28
• Study First Submitted QC: 2020-05-26
• Study First Posted: 2020-05-28
• Study Start: 2020-07-01
• Primary Completion: 2023-11-24
• Study Completion: 2023-11-24
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-14
• Last Update Posted: 2023-12-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 52

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. 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.
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.
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.

Exclusion Criteria

1. Patients who, in the investigator's opinion, have progressed rapidly on their previous anticancer treatment (e.g., did not achieve any response [CR, PR, or SD]).
2. Has brain metastases (unless they have received prior treatment and are controlled and stable for at least 6 weeks before study enrolment) or leptomeningeal spread of disease.
3. Has positive serological test for hepatitis C virus (HCV), hepatitis B virus (HBV), surface antigen (HBsAg), positive HBV core antibody. Human immunodeficiency virus (HIV).
4. Has other concomitant or prior malignant disease,
5. Has an active, known or suspected autoimmune disease.
6. Is receiving systemic immunosuppression including systemic steroids or the use of immunosuppressive agents for any concurrent condition.
7. Has known allergy to aminoglycosides or kanamycin or any study treatment component.
8. Has history of toxic shock syndrome.
9. Has history of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organising pneumonia, immune enteritis or active pneumonitis.
10. Has evidence or history of clinically significant cardiac disease including congestive heart failure
11. Has ongoing toxicity from prior therapy
12. Has severe infections within 4 weeks prior to study start
13. Current participation in a clinical trial
14. Has received investigational drug within 30 days before study entry.
15. Has received vaccination against infections within 30 days before study entry.
16. Has had prior treatment with CD137, anti-PD-1, or anti-PD-L1 therapeutic antibody or other immune checkpoint targeting agents.
17. Has known hypersensitivity to any component of the atezolizumab or VB10.16 formulation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination Therapy	Atezolizumab	VB10.16 vaccinations. 11 intramuscular (i.m.) vaccinations for up to 48 weeks from first vaccination. 5 vaccinations of 3 mg VB10.16 during the first 12 weeks, followed by vaccination every 6 weeks for up to 48 weeks + Atezolizumab (1200 mg) intravenous (i.v.) infusion every 3 weeks.
Combination Therapy	VB10.16	VB10.16 vaccinations. 11 intramuscular (i.m.) vaccinations for up to 48 weeks from first vaccination. 5 vaccinations of 3 mg VB10.16 during the first 12 weeks, followed by vaccination every 6 weeks for up to 48 weeks + Atezolizumab (1200 mg) intravenous (i.v.) infusion every 3 weeks.

Primary Outcome Measures

Name	Time	Method
Overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at any time during the study	48 weeks (1 year follow-up)	ORR as assessed by RECIST v1.1
Incidence and severity of adverse events (AEs)	48 weeks (1 year follow-up)	The number and percentage of participants that experience an adverse event (AE

Secondary Outcome Measures

Name	Time	Method
Duration of response (DOR)	48 weeks (1 year follow-up)	Estimate the duration of response (DOR) in patients with advanced cervical cancer
Overall survival (OS)	48 weeks (1 year follow-up)	Overall survival (OS) in patients with advanced cervical cancer
Progression-free survival (PFS)	48 weeks (1 year follow-up)	Estimate the Progression-free survival (PFS) in patients with advanced cervical cancer
Evaluate immunogenicity of VB10.16 in combination with atezolizumab by analysing HPV16 E6/E7-specific cellular immune responses	48 weeks (1 year follow-up)	Systemic T-cell response

Trial Locations

Locations (21)

Cliniques Universitaires Saint-Luc; 🇧🇪 Bruxelles, Belgium

University Multiprofile Hospital For Active Treatment Sofiamed; 🇧🇬 Sofia, Bulgaria

Jagielońskie Centum Innowacji, Centrum Badań Klinicznych JCI; 🇵🇱 Kraków, Poland

Hopital de Libramont; 🇧🇪 Bruxelles, Belgium

Universitair Ziekenhuis Gent (Uz Gent); 🇧🇪 Gent, Belgium

Chu Ucl Namur; 🇧🇪 Namur, Belgium

Multiprofile Hospital for Active Treatment for Women's Health - Nadezhda Sofia; 🇧🇬 Sofia, Bulgaria

University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski"; 🇧🇬 Sofia, Bulgaria

Multiprofile Hospital for Active Treatment "Serdika"" EOOD; 🇧🇬 Sofia, Bulgaria

Nemocnice Pardubickeho Kraje Pardubicka Nemocnice; 🇨🇿 Pardubice, Czechia

University Hospital Kralovske Vinohrady; 🇨🇿 Praha, Czechia

Nemocnice Na Bulovce; 🇨🇿 Praha, Czechia

Masaryk Memorial Cancer Institute; 🇨🇿 Brno, Czechia

Universitatsklinikum Augsburg; 🇩🇪 Augsburg, Germany

University Clinic Carl Gustav Carus; 🇩🇪 Dresden, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Universitatsklinikum Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Medizinische Fakulat Mannheim Der Universitat Heidelberg; 🇩🇪 Heidelberg, Germany

Oslo University Hospital; 🇳🇴 Oslo, Norway

Wielkopolskie Centrum Onkologii; 🇵🇱 Poznań, Poland

'Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie; 🇵🇱 Warsaw, Poland