A trial to learn if volrustomig is safe and efficacious in women and young adults with locally advanced cervical cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Apr 2024 → ongoing

Decision date (initial)

2024-03-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB (Södertälje 151 85, Sweden)

External identifiers

EU CT number

2023-504374-38-00

ClinicalTrials.gov

NCT06079671

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Pharmacodynamic, Safety

To demonstrate the superiority of volrustomig relative to placebo by assessment of PFS, in all randomized participants.

Secondary objectives 13

1. To demonstrate the superiority of volrustomig relative to placebo by assessment of OS in all randomized participants.
2. To estimate the effectiveness of volrustomig relative to placebo by assessment of ORR in all randomized participants.
3. To estimate the effectiveness of volrustomig relative to placebo in terms of DoR in all randomized participants.
4. To estimate the effectiveness of volrustomig relative to placebo in terms of TFST in all randomized participants.
5. To estimate the effectiveness of volrustomig relative to placebo in terms of PFS2 in all randomized participants.
6. To estimate the effectiveness of volrustomig relative to placebo in terms of PFS by BICR in all randomized participants
7. To estimate the effectiveness of volrustomig relative to placebo on the incidence of local progression, and distant disease progression as the first documented progression event in all randomized participants.
8. To assess the PK of volrustomig.
9. To investigate the immunogenicity of volrustomig.
10. To assess the safety and tolerability profile of volrustomig compared to placebo.
11. To assess participant reported disease related symptoms in participants treated with volrustomig compared to placebo.
12. To assess participant reported physical functioning in participants treated with volrustomig versus placebo.
13. To assess participant reported global health status/QoL in participants treated with volrustomig versus placebo.

Conditions and MedDRA coding

Locally advanced cervical cancer

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003423-PIP01-23

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Female.
2. Aged at least 15 years at the time of screening. Note: Participants < 18 years of age: physical changes should be aligned with Tanner Stage III.
3. Body weight > 35 kg.
4. Histologically confirmed cervical adenocarcinoma, cervical squamous carcinoma, or cervical adenosquamous carcinoma, FIGO 2018 Stage IIIA to IVA cervical cancer, no evidence of metastatic disease.
5. Initial staging procedures performed prior to initiation of any component of definitive treatment (CCRT).
6. Provision of FFPE tumor sample to assess the PD-L1 expression.
7. Must not have progressed following CCRT, participants with persistent disease after definitive CCRT must not be amenable to other available therapies with curative intent.
8. WHO/ECOG performance status of 0 or 1; duration of life expectancy of ≥ 12 weeks.
9. Adequate organ and bone marrow function.
10. Capable of providing signed informed consent.

Exclusion criteria 17

1. Diagnosis of small cell (neuroendocrine) or mucinous adenocarcinoma of cervical cancer.
2. Evidence of metastatic disease.
3. Intent to administer a fertility-sparing treatment regimen.
4. History of organ transplant or allogenic stem cell transplant.
5. History of active primary immunodeficiency or active or prior documented autoimmune or inflammatory disorders.
6. Uncontrolled intercurrent illness.
7. History of another primary malignancy except for a) Malignancy treated with curative intent with no known active disease ≥2 years before the first dose of study intervention; b) Adequately treated nonmelanoma skin cancer or lentigo maligna, or carcinoma in situ without evidence of disease.
8. Unresolved toxicities from previous CCRT except for irreversible toxicity that is not reasonably expected to be exacerbated.
9. Prior history or presence of vesicovaginal, colovaginal, or rectovaginal fistula.
10. History of anaphylaxis to any biologic therapy or vaccine.
11. Current or prior use of immunosuppressive medication within 14 days before the first dose of the study intervention is excluded. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection); b) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication or chemotherapy premedication) or a single dose for palliative purpose (eg, pain control); c) Physiologic doses of oral corticosteroids, ie, not exceeding 10 mg/day of prednisone (or equivalent) in the preceding 14 days.
12. Patients who have undergone a previous hysterectomy, including a supracervical hysterectomy, or will have a hysterectomy as part of their initial cervical cancer therapy.
13. Any prior (besides prior CCRT) or concurrent treatment for cervical cancer.
14. Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery.
15. Exposure to immune mediated therapy prior to the study for any indication.
16. Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention.
17. Participants with a known allergy or hypersensitivity to the study intervention, or any excipients of the study intervention.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Progression-free Survival (PFS) based on the investigator assessment in all randomized participants (FAS).
2. PFS is defined as the time from date of randomization until RECIST 1.1- defined radiological progression or histopathologically confirmed progression as assessed by the Investigator or death due to any cause, whichever occurs earlier.
3. Up to approximately 7 years

Secondary endpoints 14

1. Overall Survival (OS) in all randomized participants. OS defined as time from randomization until the date of death due to any cause.
2. Objective Response Rate (ORR) in all randomized participants. ORR is defined as the proportion of participants who have a CR or PR, as determined by the Investigator per RECIST 1. 1.
3. Duration of Response (DoR) in all randomized participants. DoR in participants with a CR or PR: Time from the date of first detection of CR or PR until the date of RECIST 1. 1- defined radiological progression or histopathologically confirmed progression.
4. Time to First Subsequent Therapy or death (TFST) in all randomized participants. TFST: The time from randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.
5. Time to second progression or death (PFS2) in all randomized participants. PFS2: The time from randomization to the earliest of the progression event (following the initial Investigator-assessed progression), after the first subsequent therapy, or death. The date of the second progression will be recorded by the Investigator in the eCRF and defined according to local standard clinical practice.
6. PFS by BICR in all randomized participants. Endpoints based on the PFS by BICR assessment according to RECIST 1.1.
7. The incidence of local progression, and distant disease progression as the first documented progression event in all randomized participants. Incidence of Local Progression, and Distant Disease Progression: Number and percentage of participants who develop local progression, distant disease recurrence.
8. PK of volrustomig The concentration of volrustomig in serum and PK parameters.
9. The immunogenicity of volrustomig. Incidence of ADAs against volrustomig in serum.
10. Safety and tolerability profile of volrustomig compared to placebo. AEs, clinical laboratory assessments, vital signs, and electrocardiograms.
11. Participant-reported disease-related symptoms. Change from baseline as measured by the EORTC IL318 (Symptom Experience subscale of the EORTC QLQ-CX24).
12. Participant reported physical functioning Change from baseline of physical functioning as measured by the PROMIS SF-PF Sc 7-day.
13. Participant-reported global health status/QoL. Change from baseline of GHS/QoL as measured by the EORTC Ill 72.
14. Up to approximately 7 years

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

6 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 66 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications