Using fecal microbiota transplantation to improve immunotherapy response in melanoma patients

Conversion of Unresponsiveness to Immunotherapy by Fecal Microbiota Transplantation in Patients With Metastatic Melanoma: a Randomized Phase Ib/IIa Trial

This study is testing if transferring gut bacteria from other melanoma patients can help those who haven't responded to immunotherapy feel better and improve their treatment results.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The Netherlands Cancer Institute (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Amsterdam)
• Trial ID: NCT05251389 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates whether transferring the microbiota from either responding or non-responding patients can enhance the effectiveness of immunotherapy in patients with advanced melanoma who have not responded to immune checkpoint inhibitors. It is a randomized double-blind intervention involving fecal microbiota transplantation (FMT) from donors who have either responded or not responded to anti-PD-1 therapy. Patients will undergo bowel clearance and receive FMT via esophagogastroduodenoscopy, followed by continued treatment with immune checkpoint inhibitors. The study aims to determine if the microbiota can influence treatment outcomes in refractory metastatic melanoma.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced stage cutaneous melanoma (stage III or IV) who have shown disease progression on anti-PD-1 therapy.

Not a fit: Patients who are not eligible include those with non-measurable disease or those with a poor performance status or inadequate organ function.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment responses in patients with advanced melanoma who currently have limited options.

How similar studies have performed: While the use of fecal microbiota transplantation in this context is novel, similar studies have shown promising results in other conditions, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

* Patients should be 18 years or older
* Patients have pathologically confirmed advanced stage cutaneous melanoma (stage III or IV) requiring systemic treatment with anti-PD-1

  * In case of stage IV disease, only patients with M1a or M1b disease are eligible.
* Patients have confirmed disease progression (≥20% increase according to RECIST1.1) on two consecutive scans with a four week interval while on anti-PD-1 treatment, of which the second scan has to be performed within 3 weeks prior to signing informed consent.
* Patients must have measurable disease per RECIST 1.1 criteria
* Patients have an ECOG performance status of 0-1 (appendix D)
* Patients have a life expectancy of \>3 months
* Patients have adequate organ function as determined by standard-of-care pre-checkpoint inhibitor infusion lab (including serum ALAT/ASAT less than three times the upper limit of normal (ULN); serum creatinine clearance 50ml/min or higher; total bilirubin less than or equal to 20 micromol/L, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 50 micromol/L)
* Patients have an LDH level of ≤1 times ULN
* Patients of both genders must be willing to use a highly effective method of birth control during treatment
* Patients must be able to understand and sign the Informed Consent document

Exclusion Criteria:

* Patients with acral, uveal or mucosal melanoma, or patients with an unknown primary
* Patients who have received treatment for their melanoma other than anti-PD-1 treatment.
* Stage IV patients with M1c or M1d disease.
* Patients with autoimmune diseases: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study (except Hashimoto thyroiditis, vitiligo, history of psoriasis, but no active disease)
* Patients with any grade 3 or 4 immune-related adverse events still requiring active immunosuppressive medication, apart from endocrinopathies that are stable under hormone replacement therapy. Patients who had developed grade 3-4 immune related toxicity, which has reverted to grade I with immunosuppressive drugs and who are off immunosuppression at least two weeks prior to enrollment are eligible
* Patients with brain or LM metastasis.
* Patients with an elevated LDH level
* Patients that have undergone major gastric/esophageal/bowel surgery (like Wipple, subtotal colectomy)
* Severe food allergy (e.g. nuts, shellfish)
* Patients with a swallowing disorder or expected bowel passage problems (ileus, fistulas, perforation)
* Severe dysphagia with incapability of swallowing 2 liters of bowel lavage
* Patients with a life expectancy of less than three months
* Patients with severe cardiac or pulmonary comorbidities (per judgement of the investigator)
* Women who are pregnant or breastfeeding
* Patients with any active systemic infections, coagulation disorders or other active major medical illnesses
* Patients with other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years
* Patients who received treatment with antibiotics in the three months prior to study enrolment, or patients we are expected to receive systemic antibiotics during the course of this study

Where this trial is running

Amsterdam

• Antoni van Leeuwenhoek — Amsterdam, Netherlands (Recruiting)

Study contacts

• Principal investigator: John Haanen, Prof — Medical Oncologist
• Study coordinator: John Haanen, Prof

Conditions Melanoma Stage III; Melanoma Stage IV