ALLOGENEIC FAECAL MICROBIOTA, POOLED for Advanced non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Participants who are at least 18 years of age on the day of signing informed consent\n- Patients who have progressed after immunotherapy or immunotherapy plus platinum-based chemotherapy (with platinum-based chemotherapy and ICI either sequentially or concomitantly).\n- Have received ATB within 60 days before and 42 days after the first ICI administration and have progressed within 6 months after the first ICI.\n- A male participant must abstain from heterosexual activity or must agree to use a contraception as detailed below (or in Appendix 2 of this protocol) during the treatment period and for at least 9 months after the last dose of CB or BIC and refrain from donating sperm during this period. (In application of the new recommendations of the CTFG)\n- A female participant is eligible to participate if she is not pregnant (see Appendix 2), not breastfeeding, and if at least one of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) as defined in Appendix 2. b) A WOCBP should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A WOCBP must agree to follow the contraceptive guidance in Appendix 2 or abstain from heterosexual activity during the treatment period and for at least 180 days, after the last dose of treatment\n- Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.\n- All participants must understand spoken and written national language\n- There are no restrictions on the number of prior lines of treatment. Patients may be included regardless of the number of previous therapies received\n- Patients must be affiliated to a social security system or beneficiary of the same\n- Have an estimated life expectancy greater than 3 months (from inclusion).\n- Meet acceptable steroid dose thresholds (i.e., not above the acceptable threshold <10 mg prednisone daily or equivalent) if receiving systemic steroids at physiologic doses\n- Have measurable disease based on RECIST 1.1 criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.\n- Have adequate organ function as defined in the Table 1 on the protocol. All screening laboratory tests must be performed within 28 days prior to the start of study treatment.\n- Histologically confirmed diagnosis of NSCLC (adenocarcinoma versus squamous cell carcinoma versus others)\n- Have metastatic or unresectable NSCLC and considered by their physician to be indicated for a new line of immunotherapy.\n- Have an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 to 2. Evaluation of ECOG-PS is to be performed within 7 days prior to the date of treatment allocation."}

Exclusion criteria

• {"criterion_text":"- Immunodeficiency or systemic steroid therapy equivalent to prednisolone >10mg/day or equivalent within 7 days prior to the first dose of trial treatment.\n- Has a known history of Hepatitis B virus (HBV, defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (HCV, considered active if HCV RNA is detected) infection. Note: no testing for HBV and HCV is required unless mandated by local health authority.\n- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.\n- Any condition which, in the Investigator’s opinion, makes it undesirable for the subject to participate in a clinical trial or which would jeopardize compliance with the protocol.\n- Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent\n- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of treatment.\n- Persistent toxicities related to prior treatment of grade greater than 1.\n- Swallowing disorders which can affect the intake of the oral pooled fecal microbiotherapy (MaaT033).\n- Active ongoing infection requiring ATB treatment.\n- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years prior to enrollment. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.\n- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.\n- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed\n- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Participants who have entered the follow-up phase of an investigational study may participate if it has been 4 weeks after the last dose of the previous investigational agent and that all study drug-related AEs have resolved to grade 1 or less.\n- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.\n- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.\n- Has a known history of Human Immunodeficiency Virus (HIV)."}

Primary endpoints

• {"endpoint_text":"- To evaluate whether combination of MaaT033 and CB can enhance DCR at weeks 12 as per the RECIST 1.1 criteria compared to BIC. The DCR is defined as the percentage of patients achieving complete response (CR), partial response (PR) or stable disease (SD) using RECIST v1.1 criteria. Confirmation of response must be demonstrated with an assessment 4-8 weeks from the initial response assessment (iRECIST).","definition_or_measurement_approach":"DCR defined as percentage of patients achieving CR, PR or SD using RECIST v1.1; confirmation of response required by an assessment 4-8 weeks from the initial response assessment (iRECIST)."}

Secondary endpoints

• {"endpoint_text":"- To evaluate Whether combination of MaaT033 and CB can increase DCR/ORR at 12, 24, 36 and 60 months. The ORR is defined as the rate of CR or PR as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria","definition_or_measurement_approach":"ORR defined as rate of CR or PR per RECIST v1.1; assessments at 12, 24, 36 and 60 months."}
• {"endpoint_text":"- To evaluate whether combination of MaaT033 and CB can increase PFS. The PFS is defined as the time from random assignment to the progression, or death due to any cause, whichever occurs first.","definition_or_measurement_approach":"PFS defined as time from random assignment to progression or death from any cause (whichever first)."}
• {"endpoint_text":"- To evaluate whether combination of MaaT033 and CB can increase OS. The OS is defined as the time from random assignment to the date of death due to any cause, or to the date of censoring at the last time the subject was known to be alive","definition_or_measurement_approach":"OS defined as time from random assignment to date of death from any cause or date of censoring at last known alive."}
• {"endpoint_text":"- Whether combination of MaaT033 and CB can increase the DoR. The DoR is defined as the time from the first confirmed patient response (CR or PR) to disease progression (or death from any cause).","definition_or_measurement_approach":"DoR defined as time from first confirmed CR or PR to disease progression or death from any cause."}
• {"endpoint_text":"- Incidence of AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), death, and laboratory abnormalities related to MaaT033 and CB versus BIC, using the National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0. Safety parameters include all SAEs or non-serious adverse events (AEs) and deaths graded using the NCI-CTCAE v5.0 (Common Terminology Criteria for AEs).","definition_or_measurement_approach":"Safety assessed by incidence of AEs/TEAEs/SAEs/deaths and laboratory abnormalities graded per NCI-CTCAE v5.0."}
• {"endpoint_text":"- To evaluate the effect(s) of the combination of MaaT033 and CB versus BIC on the composition of gut microbiota, on blood inflammation parameters, on systemic and tumor immunity (blood and tumor deposits), and on systemic and gut metabolism at baseline prior to 1st dose of MaaT033, prior to first dose of CB, at weeks 12 and 24 during treatment period, and again at months 12 and 24 after randomization.","definition_or_measurement_approach":"Composition and biomarkers measured at specified timepoints: baseline, prior to CB, weeks 12 and 24, and months 12 and 24 after randomization."}
• {"endpoint_text":"- To identify pathophysiological surrogates of a successful MaaT033 and restoration of the ORR among a rich multi-omics database (metagenomics, metabolomics, immunomics/inflammation, epithelial/endothelial barrier markers).","definition_or_measurement_approach":"Exploratory multi-omics analyses (metagenomics, metabolomics, immunomics/inflammation, epithelial/endothelial markers) to identify surrogates of MaaT033 engraftment and ORR restoration."}

France

Earliest CTIS Part Ii Submission Date

28-03-2025

Latest Decision Or Authorization Date

11-04-2025

Processing Time Days

14

Number Of Sites

14

Number Of Participants

162

Primary sponsor

Full Name

Institut Gustave Roussy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France