Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Nivolumab

Vancomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment.

Participants will undergo a 4-day lead-in pretreatment with antibiotic (vancomycin) to prime the gut microbiome for engraftment of the oral microbiome study intervention, then SER-401 and nivolumab treatment.

Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout.

Placebo for antibiotic

Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout.

Vancomycin pretreatment

Nivolumab (480 mg) will be administered intravenously (IV) according to institutional guidelines every 4 weeks for up to 12 cycles. A cycle is defined as 4 calendar weeks.

Administered once a day for 7 days during the lead-in phase, followed by once a day for 8 weeks during the microbiome/anti-PD-1 treatment phase.

Matching Placebo for SER-401

SER-401

Parker Institute for Cancer Immunotherapy

This study is designed to evaluate the safety and tolerability of treatment with oral microbiome study intervention (SER-401) or matching placebo in combination with anti-programmed cell death 1 (anti-PD-1) therapy (nivolumab) in participants with unresectable or metastatic melanoma. The study also intends to assess clinical outcomes, the impact of microbiome study intervention administration on the microbiome profile, and its association with clinical and immunological outcomes.

This is a Phase 1b, multicenter, randomized, placebo-controlled, blinded study in adult participants with anti-PD-1 therapy naïve, unresectable or metastatic melanoma to evaluate the safety and tolerability of SER-401, or matching placebo in combination with anti-PD-1 therapy (nivolumab). Prior to initiating microbiome study intervention and nivolumab, participants will undergo an antibiotic or antibiotic placebo treatment lead-in to prime the gut microbiome for engraftment of the oral microbiome study intervention. Study intervention groups will be assessed for safety, changes in the microbiome, changes in the percentage of tumoral CD8 T cells, and antitumor activity. Participants must have measurable disease that can be biopsied and consent to baseline and on-treatment biopsies, as well as stool and blood biomarker collection throughout the study.

Participants will be randomly assigned in a 2:1 ratio to oral microbiome study intervention or matching placebo. Nivolumab will be administered open-label as standard of care to all groups. Investigators, site personnel, and participants will remain blinded to the assignment of microbiome study intervention throughout the course of the study. Select Sponsor personnel, including but not limited to the Medical Monitor, Clinical Scientists, Biostatistician, and Patient Safety, will be unblinded to treatment assignment for ongoing safety monitoring.

Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention

A Multicenter Phase 1b Randomized, Placebo-controlled, Blinded Study to Evaluate the Safety, Tolerability and Efficacy of Microbiome Study Intervention Administration in Combination With Anti-PD-1 Therapy in Adult Patients With Unresectable or Metastatic Melanoma

Defined as complete response (CR) or partial response (PR) as best response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 assessment.

Defined as CR, PR, or stable disease (SD) for ≥ 24 weeks as best response by RECIST v1.1.

Defined as the time from randomization to date of first documented progression of disease, date of death due to any cause, or date of most recent participant contact that documented progression-free status

Defined as the time from randomization until death or last contact if still alive at the time of final data collection (after completion of anti-PD-1 therapy).

Defined as time from date of documented CR or PR to date of first documented progression of disease, date of death due to any cause, or date of most recent participant contact that documented response (ie, scan date).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention	NCT03817125	Metastatic Mela...	Placebo for ant... Vancomycin pret... Nivolumab Matching Placeb... SER-401	18 Years -	Parker Institute for Cancer Immunotherapy
Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention	NCT03817125	Metastatic Mela...	Placebo for ant... Vancomycin pret... Nivolumab Matching Placeb... SER-401	18 Years -	Parker Institute for Cancer Immunotherapy

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