Immunotherapy Master Trial for Advanced Cancers

NCT07431073 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: UC-IMM-25112025-522655-26-00
• Study Type: interventional
• Target: 275
• Locations: 0 countries
• Sites: N/A

Brief Summary

Over the past decade, cancer immunotherapy has profoundly transformed oncology by harnessing the patient's immune system to target tumors. These therapies have demonstrated the potential for durable responses and, in some cases, long-term remission or cure. However, despite these advances, only approximately 20-30% of patients derive significant clinical benefit from current immunotherapies. In parallel, investment in oncology drug development continues to grow, with global spending projected to reach $307 billion by 2026. Yet, the overall failure rate in oncology drug development remains extremely high, at around 95%, highlighting a critical gap between scientific innovation and clinical success. One major contributor to these failures lies in traditional drug development and regulatory paradigms, which have historically relied on cancer histology as the primary framework for patient selection and treatment evaluation. This approach is based on the flawed assumption that tumors of the same histological type share similar biological behavior and therapeutic vulnerabilities, and that localized and advanced disease are biologically comparable. In reality, tumor biology-rather than histology-plays a decisive role in determining immunotherapy efficacy. Substantial heterogeneity exists within the same cancer type, leading to widely variable patient outcomes even among individuals receiving identical treatments. The recent emergence of tumor-agnostic approvals for immunotherapies has reinforced the importance of shared biological features across cancer types. Approvals of anti-PD-1 therapies for microsatellite instability-high (MSI-H), mismatch repair-deficient (dMMR), or tumor mutational burden-high (TMB-H) cancers have demonstrated that biological characteristics can transcend tissue of origin. However, the predictive value of current companion diagnostic assays remains limited. Only 30-40% of biomarker-positive patients respond to treatment, underscoring the inadequacy of existing patient selection strategies. These limitations are partly driven by the methodologies used in industry-sponsored clinical trials, which typically rely on tumor samples processed by contract research organizations (CROs). For logistical reasons, analyses are performed on formalin-fixed paraffin-embedded (FFPE) or frozen tissues using conventional techniques such as immunohistochemistry (IHC) and DNA/RNA sequencing. While informative, these methods are often slow, complex, and insufficiently sensitive or specific to guide timely treatment decisions, particularly when results are required within the 3-4 week window following trial consent. Moreover, they offer limited insight into dynamic parameters such as target expression, saturation, and engagement during treatment. There is therefore a pressing need for innovative oncology drug development strategies that prioritize biologically driven patient selection, support tumor-agnostic approaches, and enable truly personalized cancer therapy. Addressing this need requires technologies capable of rapid, comprehensive, and functional immune and tumor profiling. METAREM is part of the broader REMISSION program, which aims to improve treatment stratification and generate early clinical evidence to support the development of novel therapies and patient selection strategies. METAREM is a master protocol designed to test innovative treatment approaches through dedicated sub-protocols in patients with unresectable locally advanced or metastatic cancers. All patients enrolled in METAREM undergo in-depth immuno-biological characterization at both tumor and blood levels using the PORTRAIT immunoprofiling platform. PORTRAIT analysis is performed on fresh whole blood and fresh tumor biopsies, enabling rapid, sensitive, and highly specific profiling of each patient's immune and tumor biology. This real-time approach overcomes the limitations of conventional tissue-based assays and allows for a comprehensive understanding of disease mechanisms at the individual level. By integrating these data, METAREM aims to stratify patients into the most appropriate therapeutic sub-protocols, thereby advancing personalized cancer treatment and supporting more efficient, biology-driven drug development.

Conditions

Advanced / Metastatic Solid Tumors; Advanced Malignancy

Keywords

Advanced Cancers; Metastatic tumors; Immunotherapy; Personalized therapy; Tumor Biology; Tumor Microenvironment

Outcome Measures

Primary Outcomes (2)

• To evaluate efficacy of novel treatment strategies to increase the patient population therapeutic index in histology-based or tumor-agnostic/biomarker-driven oncology indications.

  In the context of METAREM, increasing the therapeutic index refers to improving the effectiveness of a treatment approach assessed using an efficacy endpoint such as the rate of the patients who do not experience early disease progression during immunotherapy.

  Through all the METAREM subprotocols completion and no new subprotocol is designed, an average of 7 years

• To evaluate patient selection criteria to increase the patient population therapeutic index in histology-based or tumor-agnostic/biomarker-driven oncology indications

  The sub-protocols may be designed as exploratory or confirmatory trials to validate immune biomarkers for patient selection using PORTRAIT immunoprofiling. PORTRAIT profiling can be generated on from fresh whole blood and fresh tumor biopsies in order to allow for a rapid, sensitive and specific description of each patient's immuno-biological profile.

  Through all the METAREM subprotocols completion and no new subprotocol is designed, an average of 7 years

Study Arms (1)

Single Arm immunotherapy in Advanced Metastatic Cancers

EXPERIMENTAL

Each therapeutic METAREM sub-protocol will mention the description of intervention

Drug: METAREM is a master protocol that encompasses multiple therapeutic sub-protocols, each involving distinct interventions. Accordingly, the description of the intervention will be specified within each

Interventions

METAREM is a master protocol that encompasses multiple therapeutic sub-protocols, each involving distinct interventions. Accordingly, the description of the intervention will be specified within each DRUG

METAREM is a master protocol that encompasses multiple therapeutic sub-protocols, each involving distinct interventions. Accordingly, the description of the intervention will be specified within each individual METAREM therapeutic sub-protocol.

Single Arm immunotherapy in Advanced Metastatic Cancers

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥12 years with at least 40kg body weight or otherwise as per specified in sub-protocol.
• Note:
• When the patient is physically unable to give his/her written consent, an impartial witness a trusted person of his/her choice, independent from the investigators or the sponsor, can confirm in signing the patient's consent.
• For patients aged between \> 12 and \< 18, specific consent from legal tutors should be obtained on top of the minor consent and prior procedures.
• Patients with advanced cancer, as defined as unresectable locally advanced malignancies or metastatic cancers (including leukemias and lymphomas).
• 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).
• Eastern cooperative oncology group (ECOG) performance status between 0 and 2.
• 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.
• 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

You may not qualify if:

• 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 (both CT-scan or MRI).
• 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.
• 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 enrollment. Hormone replacement therapy with physiological doses of hydrocortisone is acceptable.
• 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.
• Administration of a live, attenuated vaccine within 4 weeks before registration.
• Radiotherapy to the chosen RECIST target lesion(s) (unless a progression after radiotherapy has been documented).
• 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).
• 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).
• Patients with evolving tumors next to cavitary or major blood vessels at high risk of massive bleeding and/or perforation.
• History of clinically significant hemoptysis within the past 3 months.
• 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.
• 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.
• History of clinically significant hemorrhagic or thromboembolic event in the past 3 months.
• 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).
• Ongoing uncontrolled endocrinopathy. Ancient endocrinopathy currently stable with substitutive therapy should not be excluded from the trial.

Sponsors & Collaborators

• UNICANCER: lead

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Aurélien MARABELLE, MD, PHD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Priyanka DEVI-MARULKAR, PhD, MBA

CONTACT

+33 (0) 06 62 53 60 43; p-devi-marulkar@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: METAREM is a phase II, non-randomized, open-label, multicentric master protocol, which includes multiple therapeutic sub-protocols that test new treatments in selected patient populations based on the tumor or host biology. Enrolment can be guided by the biological results from the PORTRAIT analysis, with specific therapeutic sub-protocols opened to improve patient outcomes.

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: February 24, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): January 1, 2034
• Last Updated: February 24, 2026

Record last verified: 2026-01