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 |
|
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 | No |
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 | No |
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. 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. |
|
E.4 | Principal 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) 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 negative 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 study entry.
5. Has an active, known or suspected autoimmune disease. Patients who required systemic immunosuppression within the past 3 months before enrolment or who have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents. (Exceptions include: patients with vitiligo; hypothyroidism stable on hormone replacement; type 1 diabetes; Grave’s disease; Hashimoto’s disease; alopecia areata; psoriasis; eczema; 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]) 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) at End of Treatment (EoT; V19) and End of Study (EoS; V21) |
|
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 | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |