Trial Outcomes & Findings for Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention (NCT NCT03817125)

Last Updated: 2024-06-06

Results Overview

Investigators recorded AEs during each participant interaction. Symptoms were evaluated by the Investigator using the CTCAE version 5.0. This system grades AEs on a 1 to 5 scale: Grades 1 and 2 indicate mild to moderate events; Grade 3 denotes severe events; Grades 4 and 5 signify life-threatening or fatal outcomes. A treatment-emergent adverse event (TEAE) is defined as any event that either occurs after the initiation of study intervention, having been absent at baseline, or, if present at baseline, appears to have worsened in severity or frequency, regardless of its relation to the intervention. Adverse events deemed 'Possibly', 'Probably', or 'Definitely' related to the intervention were labeled as treatment-related adverse events (TRAE).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2024-06-06

Participant Flow

Participant milestones

Participant milestones
Measure	SER-401 Matching Placebo/ Nivolumab Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Overall Study STARTED	6	8
Overall Study COMPLETED	4	2
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	SER-401 Matching Placebo/ Nivolumab Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Overall Study Adverse Event	1	0
Overall Study Physician Decision	0	1
Overall Study Lack of Efficacy	1	5

Baseline Characteristics

Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SER-401 Matching Placebo/ Nivolumab n=6 Participants Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=8 Participants 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.	Total n=14 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Age, Continuous	55.5 years STANDARD_DEVIATION 22.31 • n=5 Participants	66.3 years STANDARD_DEVIATION 11.73 • n=7 Participants	61.6 years STANDARD_DEVIATION 17.21 • n=5 Participants
Age, Customized	60.5 years n=5 Participants	64 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ruminococcaceae abundance-based metric at Screening Low	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Ruminococcaceae abundance-based metric at Screening High	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
ECOG Performance Score at Screening 0	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
ECOG Performance Score at Screening 1	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Cancer Stage at Initial Diagnosis IIA	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Cancer Stage at Initial Diagnosis IIC	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Cancer Stage at Initial Diagnosis IIIA	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Cancer Stage at Initial Diagnosis IIIB	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Cancer Stage at Initial Diagnosis IIIC	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Cancer Stage at Initial Diagnosis IV	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Cancer Stage at Initial Diagnosis Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Cancer Stage at Enrollment IIIA	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Cancer Stage at Enrollment IIIB	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Cancer Stage at Enrollment IIIC	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Cancer Stage at Enrollment IV	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Melanoma Subtype Acral	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Melanoma Subtype Cutaneous	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Melanoma Subtype Mucosal	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Melanoma Subtype Unknown	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: Safety Population is defined as all participants who received at least 1 dose of any study intervention

Outcome measures

Outcome measures
Measure	SER-401 Matching Placebo/ Nivolumab n=6 Participants Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=8 Participants 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Percentage of Patients With Adverse Events (AEs) Treatment-related adverse event (TRAE)	5 Participants	4 Participants
Percentage of Patients With Adverse Events (AEs) Grade 3 or Grade 4 TRAE	1 Participants	0 Participants
Percentage of Patients With Adverse Events (AEs) Grade 5 TRAE	0 Participants	0 Participants
Percentage of Patients With Adverse Events (AEs) Serious TRAE	1 Participants	0 Participants
Percentage of Patients With Adverse Events (AEs) TRAE leading to treatment discontinuation	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Participants were excluded from analysis at a specific time point if a stool sample was not collected or there was insufficient material available to run the assay.

Engraftment was defined as the number of spore-forming species detected in SER-401 that were absent in participant baseline samples, and present post-microbiome-treatment, also referred to as newly appearing dose species.

Outcome measures

Outcome measures
Measure	SER-401 Matching Placebo/ Nivolumab n=6 Participants Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=8 Participants 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species Day -7	5.33 spore-forming species Standard Deviation 7.202	1.67 spore-forming species Standard Deviation 1.862
Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species Cycle 1 Day 1	6.83 spore-forming species Standard Deviation 8.424	25.71 spore-forming species Standard Deviation 17.661
Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species Cycle 1 Day 8	7.60 spore-forming species Standard Deviation 9.209	23.29 spore-forming species Standard Deviation 5.187
Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species Cycle 2 Day 1	7.67 spore-forming species Standard Deviation 10.539	28.38 spore-forming species Standard Deviation 16.767
Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species Cycle 3 Day 1	8.50 spore-forming species Standard Deviation 12.629	29.00 spore-forming species Standard Deviation 12.853
Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species Cycle 4 Day 1	4.80 spore-forming species Standard Deviation 1.483	21.25 spore-forming species Standard Deviation 6.551
Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species Cycle 7 Day 1	11.20 spore-forming species Standard Deviation 18.349	25.33 spore-forming species Standard Deviation 8.963

SECONDARY outcome

Timeframe: Up to week 52

Objective Response Rate (ORR) is defined as the proportion of participants who attain a best overall response of complete response (CR; disappearance of all target lesions) or partial response (PR; \>=30% decrease in the sum of the longest diameter of target lesions), as determined by RECIST version 1.1. Confirmation of response by a repeat tumor assessment is not required.

Outcome measures

Outcome measures
Measure	SER-401 Matching Placebo/ Nivolumab n=6 Participants Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=8 Participants 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Objective Response Rate (ORR)	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to week 52

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

Outcome measures

Outcome measures
Measure	SER-401 Matching Placebo/ Nivolumab n=6 Participants Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=8 Participants 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Disease Control Rate (DCR)	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 2 years

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

Outcome measures

Outcome measures
Measure	SER-401 Matching Placebo/ Nivolumab n=6 Participants Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=8 Participants 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Progression-free Survival (PFS)	15 month Interval 3.3 to The upper limit of the 95% CI is not available due to an insufficient number of participants with an event.	5.2 month Interval 2.2 to The upper limit of the 95% CI is not available due to an insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to 2 years

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).

Outcome measures

Outcome measures
Measure	SER-401 Matching Placebo/ Nivolumab n=6 Participants Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=8 Participants 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Overall Survival (OS)	NA month Interval 13.7 to Median OS and the upper limit of the 95% CI are not available due to an insufficient number of participants with an event (i.e. death).	21.1 month Interval 9.1 to The upper limit of the 95% CI is not available due to an insufficient number of participants with an event (i.e. death).

SECONDARY outcome

Timeframe: Up to 2 years

Population: The overall number of participants evaluated for duration of response includes only those who achieved a complete (CR) or partial response (PR) as per RECIST v1.1.

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).

Outcome measures

Outcome measures
Measure	SER-401 Matching Placebo/ Nivolumab n=4 Participants Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=2 Participants 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Duration of Response	NA month Interval 5.7 to Median duration of response and the upper limit of the 95% CI are not available due to an insufficient number of participants with an event.	NA month Median duration of response and the upper and lower limits of the 95% CI are not available due to an insufficient number of participants with an event.

SECONDARY outcome

Timeframe: At cycle 2 (each cycle is 28 days)

Population: Only participants with available CD8 values at both baseline at Cycle 2 are included in the analysis.

Absolute change in the percentage of CD8 cells in tumor tissue from baseline at Cycle 2.

Outcome measures

Outcome measures
Measure	SER-401 Matching Placebo/ Nivolumab n=1 Participants Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=2 Participants 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Absolute Change in the Percentage of CD8 Cells in Tumor Tissue From Baseline at Cycle 2.	62.7 percentage of CD8 cells Interval 62.7 to 62.7	27.1 percentage of CD8 cells Interval 17.6 to 36.6

Adverse Events

SER-401 Matching Placebo/ Nivolumab

Serious events: 1 serious events

Other events: 6 other events

Deaths: 1 deaths

SER-401/ Nivolumab

Serious events: 1 serious events

Other events: 8 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	SER-401 Matching Placebo/ Nivolumab n=6 participants at risk Participants will undergo a 4-day lead-in pretreatment with antibiotic placebo, then matching placebo for SER-401 and nivolumab (480 mg) treatment. Placebo for antibiotic: Placebo for antibiotic will be administered orally four times a day for 4 days, followed by a 2-3 day washout. Nivolumab: 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. Matching Placebo for SER-401: 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.	SER-401/ Nivolumab n=8 participants at risk 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. Vancomycin pretreatment: Vancomycin (125mg) will be administered orally four times a day, followed by a 2-3 day washout. Nivolumab: 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. SER-401: 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.
Endocrine disorders Primary adrenal insufficiency	0.00% 0/6 • All AEs were collected from the start of the study intervention until 100 days after the last dose of the study intervention, up to 2 years. Deaths were collected up to 2 years from the initiation of study intervention. Serious Adverse Events and Other (Not Including Serious) Adverse Events include both treatment-related and non-treatment-related events.	12.5% 1/8 • Number of events 1 • All AEs were collected from the start of the study intervention until 100 days after the last dose of the study intervention, up to 2 years. Deaths were collected up to 2 years from the initiation of study intervention. Serious Adverse Events and Other (Not Including Serious) Adverse Events include both treatment-related and non-treatment-related events.
Gastrointestinal disorders Gastritis	16.7% 1/6 • Number of events 1 • All AEs were collected from the start of the study intervention until 100 days after the last dose of the study intervention, up to 2 years. Deaths were collected up to 2 years from the initiation of study intervention. Serious Adverse Events and Other (Not Including Serious) Adverse Events include both treatment-related and non-treatment-related events.	0.00% 0/8 • All AEs were collected from the start of the study intervention until 100 days after the last dose of the study intervention, up to 2 years. Deaths were collected up to 2 years from the initiation of study intervention. Serious Adverse Events and Other (Not Including Serious) Adverse Events include both treatment-related and non-treatment-related events.

Other adverse events

Additional Information

Ute Dugan

Parker Institute for Cancer Immunotherapy

Phone: 203-379-6757

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place