Neo-adjuvant Immunotherapy Master Trial for Localized Cancers

NCT07262489 | Recruiting Phase 2 DMC

• 2 other identifiers: UC-IMM-25092025-522127-95-00
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Most cancer treatments are developed without knowing whether the drug's targets are actually present in a patient's tumor or whether the patient is likely to benefit from the treatment. In addition, the immune environment surrounding the tumor changes significantly during the course of the disease, and the body's immune response to cancer tends to become less effective in later stages. Currently, standard blood tests provide only basic information about a patient's immune, inflammatory, and metabolic systems. These tests do not offer a comprehensive picture of how each person's immune system is functioning. Similarly, traditional tests on tumor samples-which require frozen or preserved tissue and take a long time to process-are not fast enough to guide treatment decisions during clinical trials. NEOREM is a "Master Protocol" which includes multiple therapeutic sub-protocols testing new immunotherapy strategies. (Immunotherapy is a type of cancer treatment that helps the immune system fight cancer.) Neoadjuvant immunotherapies are treatments given before surgery. Their goals are to shrink the tumor to make it easier to remove, strengthen the immune system's ability to fight cancer, increase the chances of long-term recovery, and reduce the risk of the cancer returning. This master protocol focuses on cancers that are still localized (have not spread) and aims to personalize treatments based on each patient's individual immuno-biological profile. As a part of this master protocol, a rapid analysis called PORTRAIT-which stands for "Profile in Onco-Immunology for a Rapid Treatment Research Adapted to Immunity and Tumor"-will be performed using fresh blood and tumor samples from each patient. This profiling uses highly sensitive and specific techniques to accurately detect biological markers that can predict how well someone will respond to immunotherapy before surgery. NEOREM's overall goal is to test new treatment strategies and new methods of selecting patients (using the PORTRAIT immune profiling) to improve the effectiveness of current standard treatments for certain types of cancer while also reducing their side effects.

Conditions

Localized Cancer

Keywords

Neo-adjuvant immunotherapy; Localized cancers; Tumor biology

Outcome Measures

Primary Outcomes (3)

• The main objective is 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 NEOREM, increasing the therapeutic index means enhancing the effectiveness of a treatment strategy-measured through efficacy endpoints - as complete pathological response,pCR, defined as the complete absence of viable tumor cells or major pathological response i.e. less than 10% viable tumor cells in the surgical specimen - within patient groups most likely to benefit, while reducing toxicity risks in those unlikely to respond.

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

• The main objective is to evaluate safety of novel treatment strategies to increase the patient population therapeutic index in histology-based or tumor-agnostic/biomarker-driven oncology indications

  Safety measurements will include the percentage of patients whose surgery was delayed beyond the planned timeline, due to treatment-related adverse events.

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

• The main objective is 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 NEOREM subprotocols completion and no new subprotocol is designed, an average of 7 years

Study Arms (1)

Single Arm immunotherapy in Localized Cancers

EXPERIMENTAL

Each therapeutic sub-protocol will mention the description of the intervention(s) administered

Drug: Each therapeutic NEOREM sub-protocol will mention the description of intervention

Interventions

Each therapeutic NEOREM sub-protocol will mention the description of intervention DRUG

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

Single Arm immunotherapy in Localized 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, a trusted person of his/her choice, independent from the investigator 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.
• Localized solid malignancy that is eligible to receive neo-adjuvant therapy and has medical unmet needs related to disease-free survival, overall survival or quality of life.
• Note: Specific sub-protocols could enroll patients with inoperable tumors with the aim of downstaging them to become operable.
• Having a measurable disease (i.e. at least one measurable lesion according to RECIST v1.1 for solid tumors.
• Eastern cooperative oncology group (ECOG) performance status between 0 and 2.
• Patients amenable to undergo blood draw and tumor biopsy procedures.
• 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 trial treatment.
• Platelets ≥100 000 cells/mm³
• Hemoglobin ≥ 9.0 g/dL

You may not qualify if:

• Cancer patients with advanced stages and/or distant metastasis (unless curable oligometastatic disease). Some sub-protocols could enroll patients with loco-regional (N+) stages amenable to curative intention strategies.
• 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 enrolment. 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 prior to enrolment.
• 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 local treatments which could hamper the safety or efficacy assessment of the therapy tested (for previous disease).
• Patients with evolving tumors next to cavitary or major blood vessels at high risk of massive bleeding and/or perforation.
• 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.
• Other malignancies within the past 5 years other than basal cell skin cancer or carcinoma in situ of the cervix. A history of more than 3 years 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.

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (1)

Gustave Roussy

Villejuif, 94800, France

RECRUITING

Central Study Contacts

Priyanka DEVI-MARULKAR, PhD, MBA

CONTACT

+33 (0) 6 62 53 60 43; p-devi-marulkar@unicancer.fr

Study Design

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

Model Details: NEOREM includes a series of Phase 2 clinical trials that are not randomized. These trials are testing new immunotherapy strategies for localized solid malignancies that are eligible to receive neo-adjuvant therapy and have medical unmet needs related to disease-free survival, overall survival or quality of life. Each patient will undergo PORTRAIT immune profiling before starting neoadjuvant treatment, and again during treatment (at the time of surgery), using fresh blood and tumor tissue samples. This is done to closely study the biological features of the tumor. The progress of the disease and how well the treatment is working will be monitored through medical imaging and evaluated using RECIST v1.1 criteria-a standard method used to measure how tumors respond to treatment. After surgery, a standard adjuvant treatment (an additional therapy to help prevent the cancer from returning) may be recommended by the doctor. Patients will be followed for up to five years.

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: December 3, 2025
• Study Start: January 21, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2034
• Last Updated: February 10, 2026

Record last verified: 2025-09

Locations

FR (1)