Study comparing the standard administration of immunotherapy (IO) versus the same agent administered each three months in patients with locally advanced or metastatic cancer in response after 6 months of standard IO

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Jan 2022 → 7 May 2026

Decision date (initial)

2024-07-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PHRC

External identifiers

EU CT number

2024-513707-14-00

EudraCT number

2021-000615-23

ClinicalTrials.gov

NCT05078047

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate the non-inferiority in term of PFS of administration of reduced dose intensity of IO versus standard IO for patients in response after 6 months of standard IO.

Secondary objectives 11

1. Cost-effectiveness
2. Immune progression-free survival using iRECIST or imPERCIST
3. Objective response rate at 12 and 24 months post-randomization
4. Overall survival
5. Duration of response at 12 months post-randomization
6. Quality of life (self-reported EORTC QLQ-C30, and the EQ-5D-5L questionnaires)
7. Anxiety and fear of relapse using specific questionnaires
8. Safety profile
9. Pharmacokinetics study: To measure the IO’s residual concentrations in plasma (trough levels).
10. Immune monitoring study: To identify immune biomarkers of long-term response allowing IO dose reduction.
11. Circulating tumour DNA study: To assess circulating mutation burden and mutation profile at baseline and their correlation to treatment efficacy

Conditions and MedDRA coding

Only patients with oncologic locally advanced or metastatic tumour (lung cancer, renal cell cancer (except IMDC favorable-risk treated Tyrosine Kinase Inhibitor [TKI] / immunotherapy [IO] combination), head and neck cancer, urothelial carcinoma, triple negative breast cancer, Merkel cancer, melanoma, hepatocellular carcinoma, colorectal carcinoma with microsatellite instability [MSI], esophageal squamous cell carcinoma, endometrial carcinoma, or cervical cancer, gastric/gastro-esophageal junction/esophageal adenocarcinoma, basal cell carcinoma or squamous skin carcinoma) in partial or complete response (except for melanoma, only patients in partial response) after 6 months of standard IO treatment (monotherapy or previously in combination with other immunotherapy (ipilimumab) or chemotherapy or continuous combination with pemetrexed or bevacizumab or TKI).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Patients must have signed a written informed consent form prior to any trial specific procedures.
2. Patient aged ≥18 years old.
3. Metastatic disease (or locally advanced disease not suitable for local treatment) of initial tumor histologically confirmed including : lung cancer, renal cell cancer, head and neck cancer, urothelial carcinoma, triple negative breast cancer, Merkel cancer, hepatocellular carcinoma, melanoma, colorectal carcinoma with microsatellite instability [MSI], esophageal squamous cell carcinoma, endometrial carcinoma, cervical cancer, gastric/gastro-oesophageal junction adenocarcinoma, basal cell carcinoma, squamous skin carcinoma or biliary tract cancer.
4. Patients in partial or complete response after 6 months of standard immunotherapy (whatever the line of therapy) according to the RECIST v1.1 or PERCIST v1.0 criteria (confirmed by local radiological assessment). For metastatic melanoma only patients in partial response. Patients with metastatic or advanced cancer treated by immunotherapy as maintenance therapy can be included without any lesion at IO initiation. In this case, response after 6 months of standard immunotherapy will be evaluated by the nonappearance of a new lesion.
5. Eligible to maintain the same standard IO treatment
6. Patient with ECOG performance status ≤1.
7. Patients with brain metastases are allowed, provided they are stable according to the following definitions: treated with surgery or stereotactic radiosurgery and without evidence of progression prior to randomization and have no evidence of new or enlarging brain metastases.
8. Patients treated by IO previously combined with chemotherapy are allowed
9. Patients with TKI-IO or pemetrexed-IO or bevacizumab-IO are allowed
10. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for premenopausal patients
11. Both sexually active women of childbearing potential and males (and their female partners ) patients must agree to use adequate contraception method for the duration of the study treatment and after completing treatment according to the most recent version of the IO SmPC.
12. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.
13. Patient must be affiliated to a Social Security System

Exclusion criteria 6

1. Metastatic melanoma in complete response
2. Hematologic malignancies (leukaemia, myeloma, lymphoma…)
3. Active infection requiring systemic therapy.
4. Patients enrolled in another therapeutic study within 30 days before the inclusion in and during MOIO study
5. Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study.
6. Person deprived of their liberty or under protective custody or guardianship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) is calculated from the date of randomization to the date of first progression or death from any cause, whichever occurs first. Progression will be determined locally by the investigator through the use of RECIST v1.1 in case of lesions identified at baseline (for patients assessed by PET-scan, progression will be determined according to PERCIST criteria v1.0).

Secondary endpoints 11

1. Incremental cost-effectiveness ratio (ICER) expressed as a cost per quality-adjusted life year (QALY) gained at 36 months
2. Immune progression-free survival (iPFS) calculated from the date of randomization to the date of disease progression criteria (iPD) or death from to any cause, whichever occurs first. Immune progression (iPD) will be determined locally by the investigator through the use of iRECIST or imPERCIST criteria in case of lesions identified at baseline.
3. Objective response rate (ORR) defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1 or PERCIST v1.0 criteria at 12 and 24 months post-randomization considering patients who switch from study treatment to any other cancer treatment within 12 and 24 months post-randomization as failures.
4. Overall survival calculated from the date of randomization to the date of death from any cause
5. Duration of response (DoR) defined as the time from randomization to first documented response until progression disease progression or death, whichever occurs first
6. Quality of life mean score of self-reported EORTC QLQ-C30, and the EQ-5D-5L questionnaires at inclusion visit (pre-randomization), 3, 6, 9, 12, 15, 18, 24 and 36 months post-randomization.
7. Evaluation of anxiety and fear of relapse using specific questionnaires at 3, 6, 9, 12, 15, 18, 24 and 36 months post-randomization.
8. Number, frequency and severity of adverse events according to CTCAE v5.0 at 12 months and 3 years post-randomization.
9. Pharmacokinetic study: Comparison of IO’s residual concentrations in plasma between treatment arms.
10. Immune monitoring: Comparison of soluble forms of immune checkpoints in plasma and immune cells population in PBMC between treatment arms.
11. Circulating tumour DNA study: Circulating tumor load and tumor mutation burden (TMB) will be explored using panel-based NGS on plasma samples collected at inclusion and also at progression when available in each treatment arm. The prognostic impact of specific mutation signatures will also be explored

Investigational products

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

Test 7

Comparator 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 37 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 8 files

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

Application history

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