Efficacy and Safety of VB10.16 Alone or in Combination With Atezolizumab in Patients With Advanced Cervical Cancer.

NCT06099418 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: VB-C-04GOG-3091
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multi-center study in patients with recurrent or metastatic HPV16-positive, PD-L1 positive cervical cancer who has progressed during or after treatment with the first-line standard of care (pembrolizumab with chemotherapy with/without bevacizumab). The trial is designed to investigate VB10.16 alone or in combination with the immune checkpoint inhibitor, atezolizumab. The trial consist of 2 parts: the first part which investigates VB10.16 + placebo versus VB10.16 + atezolizumab. Approximately 30 patients will be included in each group. The goal of this part is to evaluate which of the two treatments is the best. The second part of the study will select the best treatment from part 1 and investigate the safety and efficacy of additional 70 patients.

Conditions

HPV-Related Cervical Carcinoma; HPV-Related Malignancy; Cervical Cancer

Keywords

Recurrent; metastatic; HPV16-positive; PD-L1 positive

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1 as assessed by blinded independent central review (BICR).

  Up to 1 year

Secondary Outcomes (22)

• Objective Response Rate (ORR)

  Up to approximately 2 year

• Duration of Response (DOR)

  Up to approximately 2 years

• Duration of Response (DOR)

  Up to approximately 2 years

• Time to Response (TTR)

  Up to approximately 2 years

• Disease Control Rate (DCR)

  Up to approximately 2 years

Study Arms (2)

VB10.16 + placebo

EXPERIMENTAL

9 mg VB10.16 via i.m. needle free injections in the deltoid muscles and quadricep or gluteus muscle. Placebo will be given via IV infusions.

Biological: VB10.16; Drug: Placebo

VB10.16 + atezolizumab

EXPERIMENTAL

9 mg VB10.16 via i.m. needle free injections in the deltoid muscles and quadricep or gluteus muscle. Atezolizumab will be given via IV infusions.

Biological: VB10.16; Drug: Atezolizumab Injection [Tecentriq]

Interventions

VB10.16 BIOLOGICAL

Intramuscular (i.m.) administrations of VB10.16 every 3 weeks (Q3W) during a 12-week induction period, followed by a maintenance period with administrations every 6 weeks (Q6W) from Week 13 until Week 49. A total of up to 11 i.m. administrations will be given. VB10.16 will be administered via Pharma Jet® Stratis 0.5 mL needle free injection system.

VB10.16 + atezolizumab; VB10.16 + placebo

Atezolizumab Injection [Tecentriq] DRUG

Intravenous (IV) infusions of atezolizumab (saline solution) every 3 weeks.

VB10.16 + atezolizumab

Placebo DRUG

Intravenous (IV) infusions of placebo (saline solution) every 3 weeks.

VB10.16 + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at ICF signature date.
• Persistent recurrent or metastatic (R/M) (stage IVB) PD-L1 positive cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology with confirmed disease progression during or after treatment with 1st line systemic standard of care pembrolizumab + platinum-containing chemotherapy +/- bevacizumab
• Participants should have received at least 4 cycles of pembrolizumab.
• Planned treatment start should be within 12 weeks of documented radiographic disease progression.
• Participants should have received no more than 1 prior systemic anti-cancer treatment regimen for recurrent/metastatic cervical cancer (pembrolizumab + chemotherapy +/- bevacizumab).
• PD-L1-positive tumor confirmed by Ventana SP263 clone (the Food and Drug Administration approved companion diagnostic test for atezolizumab in other indications), with tumor area positivity ≥5% in designated central laboratory
• HPV16-positive tumor confirmed by nucleic acid amplification test in designated central laboratory
• At least 1 measurable lesion per RECIST v1.1 as assessed by Blinded Independent Central Review.
• Overall function and organ function:
• ECOG performance status (PS) ≤1
• Gustave Roussy Immune (GRIm) score ≤1

You may not qualify if:

• Disease specific:
• Has disease that is suitable for local therapy with curative intent.
• Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the opinion of the investigator.
• Neuroendocrine carcinoma of the cervix.
• Prior, concurrent or future interventions:
• Radiotherapy (or other non-systemic therapy) ≤14 days prior to VB10.16 treatment start, or the patient has not fully recovered (i.e., Grade ≤1 at baseline) from AEs due to a previously administered treatment.
• Has received prior surgery or prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment.
• Prior solid organ or tissue transplantation (except corneal transplant).
• Prior autologous or allogeneic hematopoietic stem cell transplantation.
• Prior chimeric antigen receptor T-cell (CAR-T) therapy.
• Prior therapy with a monoclonal antibody, bispecific antibody, or antibody fragment (or other molecule with similar mechanism of action) that engages with stimulatory or co-inhibitory molecules on T cells (e.g., CD3, CTLA-4, PD-1, 4-1BB/CD137), except pembrolizumab in the metastatic setting.
• Prior therapy with CPI in the locally advanced setting.
• Prior administration with tisotumab vedotin.
• Administration of a live (attenuated replicating organism) or non-live (pathogen component or killed whole organism) vaccine, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine within 30 days prior to VB10.16 treatment start.
• Prior administration with a therapeutic HPV16 vaccine.

Sponsors & Collaborators

• Nykode Therapeutics ASA: lead
• Roche Pharma AG: collaborator
• GOG Foundation: collaborator

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Recurrence; Neoplasm Metastasis

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Study Officials

• Ritu Salani, MD MBA

  UCLA Division of Gynecologic Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A modified randomized phase 2 selection ('pick-the-winner') design with a margin of practical equivalence will be implemented to monitor efficacy of the two individual arms, and to decide which of the two arms that may be continued further based on the primary endpoint of confirmed ORR.

Study Record Dates

• First Submitted: October 19, 2023
• First Posted: October 25, 2023
• Study Start: April 18, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: September 20, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share