METAREM / META-1 - METAREM :Immunotherapy Master Trial for Advanced Cancers / META-1: Immunotherapy without chemotherapy for advanced lung cancer patients with high PD-L1 Levels.

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]

Decision date (initial)

2026-04-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Agence Nationale de Recherche (ANR)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of the METAREM master protocol is to test novel treatment strategies and patient selection criteria (notably via PORTRAIT screening) to increase the patient population therapeutic index for histology based or tumor-agnostic/biomarker-driven oncology indications.

The primary objective of the META-1 sub-protocol is to evaluate the rate of patients without early progression upon anti-PD1 monotherapy by selecting patients with a baseline plasma PTI score of 0 in patients with advanced/metastatic NSCLC with PD-L1 TPS >50%.

Secondary objectives 5

1. META-1: To assess treatment activity in patients with a baseline plasma PTI score = 0 in terms of: Objective Response Rate (ORR), Durable Clinical Benefit (DCB), Overall Survival (OS), Progression-free survival (PFS).
2. META-1: To assess the safety of treatment using the NCI-CTCAE v6.0 and the PRO-CTCAE questionnaire in patients with baseline plasma PTI score = 0.
3. META-1: To determine the quality of life of patients for patients with a baseline plasma PTI score = 0 and patients with a baseline plasma PTI score ≥1.
4. META-1: To compare progression-free survival (PFS) between patients with baseline plasma PTI score = 0 to patients with baseline PTI score ≥1 and according to treatment modality.
5. META-1: To assess the safety using the NCI-CTCAE v6.0 and the PRO-CTCAE questionnaire in patients with baseline PTI score ≥1.

Conditions and MedDRA coding

METAREM:Patients with advanced cancer, as defined as unresectable locally advanced malignancies or metastatic cancers (including leukemias and lymphomas). META-1: Patients in first-line therapy for advanced metastatic NSCLC with PD-L1 Tumor Proportion Score (TPS) >50%, without EGFR/ ALK/ ROS1 mutations and irrespective of their histological subtype (squamous or non-squamous)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. METAREM: Age ≥12 years with at least 40kg body weight or otherwise as per specified in sub-protocol.
2. METAREM: Prior to the inclusion in the METAREM master protocol, patients must have signed a written informed consent to baseline PORTRAIT and on-treatment PORTRAIT evaluation. Note a. When the patient is physically unable to give his/her written consent, an impartial witness, independent from the investigators or the sponsor, can confirm in signing the patient’s consent. b. For patients aged between > 12 and < 18, specific consent from legal tutors should be obtained on top of the minor consent and prior procedures.
3. METAREM: Patients with advanced cancer, as defined as unresectable locally advanced malignancies or metastatic cancers (including leukemias and lymphomas).
4. METAREM: Having measurable disease (i.e one measurable lesion according to RECIST v1.1 for solid tumors or one consensus method of blast quantification / minimal residual disease assessment for leukemias).
5. METAREM: Eastern cooperative oncology group (ECOG) performance status between 0 and 2.
6. METAREM: Patients amenable to undergo a blood draw procedure and a tumor biopsy procedure. For patients with more than 10% malignant cells in their bone marrow or blood, a bone marrow aspirate or blood draw could replace the tumor biopsy.
7. METAREM: Adequate organ function as defined by the following criteria: Total bilirubin ≤1.5 ULN, or ≤3.0 ULN in participants with Hepato-Cellular Carcinoma (HCC) or known Gilbert’s syndrome if the increase is predominantly due to unconjugated bilirubin. ALT ≤ 3 x ULN; if liver metastases ALT ≤ 5 x ULN, Absolute Neutrophils count (ANC) ≥ 1000 cells/mm³ in the absence of G-CSF or GM-CSF within ≤2 weeks before the first dose of study treatment. - Platelets ≥100 000 cells/mm³, Hemoglobin ≥ 9.0 g/dL, Albumin ≥ 30 g/L, Calculated creatinine clearance ≥50 mL/min/1.73 m2
8. METAREM : Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment.
9. METAREM: Both sexually active WOCBP and males (and their WOCBP partners) patients must agree to use two methods of effective contraception, one of them being a physical barrier method, or to abstain from sexual activity during the study and for the period indicated in specific sub-protocol after the last study drug administration.
10. METAREM : Patient affiliated to the French social security regimen.
11. METAREM: Patients with mental and legal ability to fully consent for undergoing the exploratory procedures (blood draws and biopsies) prior (at baseline PORTRAIT) and upon treatment and (on-treatment PORTRAIT).
12. METAREM: 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. META-1: Patients with ≥ 18 age.
14. META-1: Patients in first-line therapy for advanced metastatic NSCLC with PD-L1 Tumor Proportion Score (TPS) >50%, without EGFR/ ALK/ ROS1 mutations and irrespective of their histological subtype (squamous or non-squamous).
15. META-1: Patients with a PTI score of zero in plasma on the baseline PORTRAIT report. Note: Patients with PTI score ≥ 1 who meet all other criteria will be followed up to 36 months or death (whichever occurs first) according to standard of care.

Exclusion criteria 24

1. METAREM: Any life-threatening allergy to one of the experimental products tested in the sub-protocol where the patient is eligible. In case of allergy to contrast media, patient monitoring should be performed with alternate methods (CT-scan or MRI).
2. METAREM: History of life threatening autoimmune/immune mediated inflammatory disease, including but not limited to severe colitis, pneumonitis, Guillain-Barré syndrome, anti-phospholipid syndromes and myocarditis. Patients with a history of auto-immune endocrinopathy (hypo/hyper thyroiditis, type 1 diabetes mellitus, …) and who are stable on hormone replacement therapy are eligible for the study. Patients with a history of vitiligo, alopecia areata, cutaneous psoriasis and grade 1-2 Sjogren syndrome are eligible. Hormone replacement therapy with physiological doses of hydrocortisone is acceptable.
3. METAREM: Treatment with systemic long-term immunosuppressive medications unless otherwise specified in the specific therapeutic Sub-protocols. Those immunosuppressive drugs must have been stopped at least 4 weeks prior to enrolment.
4. METAREM: Chemotherapy, hormonotherapy, radiotherapy or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks or 5 half-life times (whatever the shortest) prior to treatment with the trial drugs.
5. METAREM: Administration of a live, attenuated vaccine within 4 weeks before registration.
6. METAREM: Radiotherapy to the chosen RECIST target lesion(s) (unless a progression after radiotherapy has been documented).
7. METAREM: Persistence of a clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or radiotherapy which could hamper the safety or efficacy assessment of the therapy tested (for previous disease).
8. METAREM: Patients with symptomatic brain metastases or leptomeningeal disease are excluded unless otherwise specified by a specific therapeutic Sub-protocol. Clinically asymptomatic brain metastases and clinically asymptomatic leptomeningeal disease are allowed (treatment with steroids prior to initiation of the trial is not allowed).
9. METAREM: Patients with evolving tumors next to cavitary or major blood vessels at high risk of massive bleeding and/or perforation.
10. METAREM: History of clinically significant hemoptysis within the past 3 months
11. METAREM: Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial.
12. METAREM: Major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned major surgery during the on-treatment study period.
13. METAREM: History of clinically significant hemorrhagic or thromboembolic event in the past 3 months.
14. METAREM: History of significant cardiovascular diseases (i.e. supraventricular tachycardia, uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion).
15. METAREM: Ongoing uncontrolled endocrinopathy. Ancient endocrinopathy currently stable with substitutive therapy should not be excluded from the trial.
16. METAREM: Other malignancies within the past 5 years other than superficial malignancies (e.g localized squamous or basal cell skin cancer) or carcinoma in situ (e.g cervix, breast, prostate, bladder) which have undergone curative therapies. A history of more than 3 years without subsequent relapse of local prostate cancer treated by surgery and without PSA elevation since surgery, or local breast carcinoma treated by surgery without relapse or resected non-muscle invasive bladder cancers are eligible.
17. METAREM: Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy. A wash out of more than 3 weeks is required after last systemic antibiotics to allow reconstitution of the microbiome. Patients infected by HIV but having efficient anti-retroviral therapy and CD4+ T-cell counts >500/mm³ are eligible. Patients with a history of HBV or HCV that are cured and have eligible liver function criteria are also eligible.
18. METAREM: Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug in case an oral drug is tested in the sub-protocol for which the patient is screened
19. METAREM: Pregnancy or breast feeding.
20. METAREM: Intake of Ganoderma Lucidum mushroom (also called “Reishi”) and/or herbal remedies and/or traditional medicines within the past weeks prior to start of study treatment or concomitantly with the trial because of their potential to increase treatment related adverse events.
21. METAREM: Any psychological, familial, sociological, geographical factors, lifestyle, behavior, clinical or biological parameters or elements in the past medical history of the patients that, according to the investigator, could preclude the ability of the trial to directly reach its objectives, or indirectly via treatment observance or study follow up. Patients with active alcoholism and/or drug abuse are excluded.
22. METAREM: Person deprived of their liberty or under protective custody or guardianship
23. META-1: Patients who have previously received an anti-PD(L)1 or anti-CTLA4 or anti-LAG- 3 or anti-TIM3 immunotherapy.
24. META-1: Patients with any Hypersensitivity to the active ingredient or to any of the excipients of Pembrolizumab or Cemiplimab.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. META-1: The primary endpoint is the rate of patients without disease progression at 12 weeks.

Secondary endpoints 5

1. META-1: An assessment of treatment activity in patients with a baseline plasma PTI score = 0 in terms of: Objective Response Rate (ORR), Durable Clinical Benefit (DCB) is defined as the percentage of patient alive andwithout disease progression (CR + PR + stable disease [SD] as assessed by the investigator according to RECIST v1.1). Overall Survival (OS). Progression Free Survival (PFS)
2. META-1: For patients with a baseline plasma PTI score = 0, safety will be evaluated according to the incidence of adverse events (AEs) graded by the National Cancer Institute - common terminology criteria for adverse events NCI-CTCAE v 6.0. The PRO-CTCAE questionnaire will be also used to assess the safety profile at weekly intervals.
3. META-1: Health-related quality of life will be evaluated through the EORTC QLQ-C30 questionnaire by collecting data at inclusion and once every 3 months until the end of the treatment in patients with a baseline plasma PTI score = 0 and patients with a baseline plasma PTI score ≥1.
4. META-1: For patients with a baseline plasma PTI score ≥1, Progression Free Survival (PFS) is defined as the time from inclusion until progressive disease assessed by the investigator according to standard of care or death from any cause, whichever occurs first. Patients without documented progression will be censored at last disease assessment or at initiation of new anticancer treatment (if applicable).
5. META-1: For patients with a baseline plasma PTI score ≥1, safety will be evaluated according to the incidence of adverse events (AEs) graded by the National Cancer Institute - common terminology criteria for adverse events NCI-CTCAE v 6.0 as per standard of care. The PRO-CTCAE questionnaire will also be used to assess the safety profile at weekly intervals.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

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 · 5 investigational sites

By country

Investigational sites

Results and documents

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

Documents 18 files

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

Application history

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