A Randomized Multicenter Phase II Trial Evaluating Oral Pooled Fecal Microbiotherapy (MaaT033) Concomitant to Cemiplimab (CB) Versus Best Investigator's Choice (BIC) in Resistance to PD-1/PD-L1 Blockade Due to Antibiotics (ATB) Uptake in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

New trial tests gut bacteria therapy with immunotherapy for advanced lung cancer

NCT: NCT07001618 · Status: RECRUITING · Phase: Phase 2 · Sponsor: Gustave Roussy, Cancer Campus, Grand Paris · Started: 2025-11-17 · Est. Completion: 2032-09

Plain English Summary

Oral Pooled Fecal Microbiotherapy (MaaT033) Concomitant to Cemiplimab Versus Best Investigator's Choice in Patients With Resistance to Treatment Due to Antibiotics Uptake With Advanced Non-small Cell Lung Cancer is a Phase 2 clinical trial sponsored by Gustave Roussy, Cancer Campus, Grand Paris studying NSCLC (Advanced Non-small Cell Lung Cancer). This trial tests if a new oral therapy using gut bacteria (MaaT033) can help patients with advanced lung cancer whose cancer has stopped responding to standard immunotherapy, especially if they've recently taken antibiotics. It is for patients with advanced non-small cell lung cancer (NSCLC) who have not responded well to previous immunotherapy treatments, particularly if antibiotic use may have contributed to this resistance. Participants will receive either the new gut bacteria therapy combined with a specific immunotherapy (Cemiplimab) or the best treatment chosen by their doctor. The gut bacteria therapy is taken orally for a week before each immunotherapy cycle. Alternative treatments for this situation might include other types of chemotherapy or different immunotherapy combinations, depending on the doctor's best judgment. The trial aims to enroll 162 participants.

Official Summary

The goal of IMMUNOLIFE2 is to overcome primary resistance to immune checkpoint inhibitors (ICIs), such as pembrolizumab or nivolumab used alone or in combination with chemotherapy, observed in patients with advanced non-small cell lung cancer (NSCLC) following antibiotic exposure, which induces intestinal dysbiosis. The reintroduction of immunotherapy with Cemiplimab, combined with oral pooled fecal microbiotherapy (MaaT033), aims to restore gut microbiota and potentially reverse resistance to ICIs. The main objective is to determine whether the combination of MaaT033 and Cemiplimab provides a superior disease control rate compared to the current best investigator's choice as comparator. Patients will be randomized to receive either: * Experimental arm: MaaT033 administered orally for one week prior to each cycle of Cemiplimab, which will be given in hospital care every 3 weeks for 6 months, followed by Cemiplimab alone thereafter; * Control arm: Best investigator's choice

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older, have advanced non-small cell lung cancer, and your cancer has progressed after immunotherapy, especially if you took antibiotics recently. You cannot join if you have active infections, certain other cancers, have had recent radiation therapy, or are on high doses of steroids. You must have a good general health status (ECOG performance status 0-2) and a life expectancy of over 3 months. Specific requirements are in place for men and women regarding contraception and pregnancy to avoid risks during the trial. This trial is studying NSCLC (Advanced Non-small Cell Lung Cancer), so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see if the combination of gut bacteria therapy and immunotherapy helps control the cancer's growth better than the standard treatment chosen by the doctor. The specific primary outcome measures are: Disease Control Rate (DCR) (At 12 weeks and confirmation 4-8 weeks from the initial response assessment.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical unmet need in advanced lung cancer by exploring a novel approach to overcome resistance to immunotherapy, which is often linked to antibiotic use and changes in gut bac Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets NSCLC (Advanced Non-small Cell Lung Cancer), where improved treatment options are needed.

Investor Insight

This trial signals a growing interest in microbiome-based therapies as a way to enhance cancer treatment efficacy, potentially opening a new market for gut health interventions in oncology. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is suitable for you, especially regarding your specific type of lung cancer and previous treatments. Understand that you will be randomly assigned to one of two treatment groups, and participation involves regular hospital visits for infusions and oral medication. Be prepared for potential side effects from both the immunotherapy and the gut bacteria therapy, and discuss any concerns with your medical team. This trial is currently recruiting participants. The trial is being conducted at 6 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

Interventions

Primary Outcomes

Secondary Outcomes

Full Eligibility Criteria

Inclusion Criteria:

1. Participants who are at least 18 years of age on the day of signing informed consent,
2. All participants must understand spoken and written national language,
3. Histologically confirmed diagnosis of NSCLC (adenocarcinoma versus squamous cell carcinoma versus others)
4. Have metastatic or unresectable NSCLC and considered by their physician to be indicated for a new line of immunotherapy.
5. 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.
6. Patients who have progressed after immunotherapy or immunotherapy plus platinum-based chemotherapy (with platinum-based chemotherapy and ICI either sequentially or concomitantly).
7. 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.
8. There are no restrictions on the number of prior lines of treatment. Patients may be included regardless of the number of previous therapies received.
9. 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)
10. 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:

    1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 2.
    2. 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.
11. 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.
12. Patients must be affiliated to a social security system or beneficiary of the same
13. Have an estimated life expectancy greater than 3 months (from inclusion).
14. 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
15. 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.
16. Have adequate organ function as defined in the Table 1. All screening laboratory tests must be performed within 28 days prior to the start of study treatment.

Exclusion Criteria:

1. Immunodeficiency or systemic steroid therapy equivalent to prednisolone \>10mg/day or equivalent within 7 days prior to the first dose of trial treatment.
2. Active ongoing infection requiring ATB treatment.
3. 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.
4. 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.
5. 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.
6. 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.
7. Has known active CNS metastases and/or carcinomatous meningitis. Participants with pre

Trial Locations

Frequently Asked Questions

What is clinical trial NCT07001618?

NCT07001618 is a Phase 2 INTERVENTIONAL study titled "Oral Pooled Fecal Microbiotherapy (MaaT033) Concomitant to Cemiplimab Versus Best Investigator's Choice in Patients With Resistance to Treatment Due to Antibiotics Uptake With Advanced Non-small Cell Lung Cancer." It is currently recruiting and is sponsored by Gustave Roussy, Cancer Campus, Grand Paris. The trial targets enrollment of 162 participants.

What conditions does NCT07001618 study?

This trial investigates treatments for NSCLC (Advanced Non-small Cell Lung Cancer). The primary condition under study is NSCLC (Advanced Non-small Cell Lung Cancer).

What treatments are being tested in NCT07001618?

The interventions being studied include: MaaT033 capsule (DRUG), Cemiplimab (DRUG), Cisplatin (DRUG), Carboplatine (DRUG), Pemetrexed (Alimta) (DRUG). MaaT033 capsule will be taken orally once a day for a week before every Cemiplimab cycle for the first 6 months of treatment.

What does Phase 2 mean for NCT07001618?

Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.

What is the current status of NCT07001618?

This trial is currently "Recruiting." It started on 2025-11-17. The estimated completion date is 2032-09.

Who is sponsoring NCT07001618?

NCT07001618 is sponsored by Gustave Roussy, Cancer Campus, Grand Paris. The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT07001618?

The trial aims to enroll 162 participants. The trial is currently recruiting and accepting new participants.

How is NCT07001618 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs none masking.

What are the primary outcomes being measured in NCT07001618?

The primary outcome measures are: Disease Control Rate (DCR) (At 12 weeks and confirmation 4-8 weeks from the initial response assessment.). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT07001618 being conducted?

This trial is being conducted at 6 sites, including Dijon; Grenoble; Paris; Suresnes and 2 more sites (France).

Where can I find official information about NCT07001618?

The official record for NCT07001618 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT07001618. This government database provides the most up-to-date and detailed information about the trial.

What is NCT07001618 testing in simple terms?

This trial tests if a new oral therapy using gut bacteria (MaaT033) can help patients with advanced lung cancer whose cancer has stopped responding to standard immunotherapy, especially if they've recently taken antibiotics. It is for patients with advanced non-small cell lung cancer (NSCLC) who have not responded well to previous immunotherapy treatments, particularly if antibiotic use may have contributed to this resistance.

Why is this trial significant?

This trial addresses a critical unmet need in advanced lung cancer by exploring a novel approach to overcome resistance to immunotherapy, which is often linked to antibiotic use and changes in gut bac

What are the potential risks of participating in NCT07001618?

Common side effects of immunotherapy can include fatigue, skin rash, and flu-like symptoms. The gut bacteria therapy may cause digestive issues like diarrhea or constipation. There's a risk that the cancer may not respond to the treatment or may progress despite the therapy. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT07001618?

Ask your doctor if this trial is suitable for you, especially regarding your specific type of lung cancer and previous treatments. Understand that you will be randomly assigned to one of two treatment groups, and participation involves regular hospital visits for infusions and oral medication. Be prepared for potential side effects from both the immunotherapy and the gut bacteria therapy, and discuss any concerns with your medical team. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT07001618 signal from an investment perspective?

This trial signals a growing interest in microbiome-based therapies as a way to enhance cancer treatment efficacy, potentially opening a new market for gut health interventions in oncology. This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.

What happens if the treatment in this trial doesn't work?

Participants will receive either the new gut bacteria therapy combined with a specific immunotherapy (Cemiplimab) or the best treatment chosen by their doctor. The gut bacteria therapy is taken orally for a week before each immunotherapy cycle. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.

Related Conditions

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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.