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
Overview
- Phase
- Phase 1
- Intervention
- Placebo for antibiotic
- Conditions
- Metastatic Melanoma
- Sponsor
- Parker Institute for Cancer Immunotherapy
- Enrollment
- 14
- Locations
- 7
- Primary Endpoint
- Percentage of Patients With Adverse Events (AEs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant must be willing to provide a baseline stool sample.
- •Histologically-confirmed Stage IV cutaneous melanoma or Stage III cutaneous, acral or mucosal melanoma that is judged inoperable. Participants with a history of uveal melanoma are not eligible.
- •Measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1; ie, defined as at least 1 lesion that can be accurately measured in at least 1 dimension \[longest diameter to be recorded\] with a minimum size of ≥ 10 mm by computerized tomography \[CT\] scan or caliper measurement on clinical exam or ≥ 20 mm by chest X-ray).
- •Malignant lymph nodes must be ≥ 15 mm in short axis when assessed by CT scan to be considered pathologically enlarged and measurable.
- •Participants must have at least one measurable lesion by RECIST and a separate lesion amenable to biopsy that has not been previously irradiated.
- •i. Participants must be willing to undergo a newly-obtained core needle or incisional biopsy at baseline (prior to antibiotic or antibiotic placebo administration). Fine needle aspiration is not acceptable.
- •Participants must be willing to undergo tumor biopsy on treatment.
- •Prior adjuvant or neoadjuvant melanoma therapy is permitted if completed at least 6 weeks prior to randomization and all related AEs have either returned to baseline or stabilized.
- •Prior anti-CTLA-4 therapy in the adjuvant setting is allowed if completed at least 12 weeks prior to the first dose of anti-PD-1.
Exclusion Criteria
- •Participants who require hemodialysis.
- •Participants with a history of another cancer in the last 5 years, except for: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; c) localized prostate cancer not requiring systemic therapy; and c) other primary tumors with no known active disease present that, in the opinion of the Investigator and the Sponsor, will not affect participant outcome in the setting of the current diagnosis.
- •Any known, untreated brain metastases. Participants with brain metastases are eligible if these have been treated, and provided:
- •Brain metastases must be stable (image-documented) 4 weeks after completion of treatment for brain metastases and require treatment with less than 10 mg/day prednisone equivalent for at least 2 weeks prior to study intervention administration.
- •Neurological symptoms should be absent or returned to baseline.
- •Prior checkpoint inhibitor therapy with anti-PD-1 or anti-PD-L1 in the adjuvant setting.
- •a. Exception: Participants with stage 3 or 4 cutaneous melanoma status post-resection who have received up to one year of adjuvant anti-PD-1 therapy who have recurred \> 6 months after their last dose of anti-PD-1 therapy are eligible.
- •Other prior systemic treatment (ie, anticancer chemotherapy, immunotherapy, or investigational agents) for unresectable or metastatic melanoma EXCEPT:
- •Prior BRAF-targeted therapy (ie, BRAF or BRAF-MEK) in the metastatic setting is allowed if completed at least 4 weeks prior to the first dose of anti-PD-
- •Prior anti-CTLA 4 therapy in the adjuvant setting are allowed if completed at least 12 weeks prior to the first dose of anti-PD-
Arms & Interventions
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.
Intervention: Placebo for antibiotic
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.
Intervention: Nivolumab
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.
Intervention: Matching Placebo for SER-401
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.
Intervention: Vancomycin pretreatment
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.
Intervention: Nivolumab
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.
Intervention: SER-401
Outcomes
Primary Outcomes
Percentage of Patients With Adverse Events (AEs)
Time Frame: Up to 2 years
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).
Secondary Outcomes
- Progression-free Survival (PFS)(Up to 2 years)
- Disease Control Rate (DCR)(Up to week 52)
- Mean Change From Baseline in the Number of Newly Appearing Spore-forming Species(Up to 2 years)
- Objective Response Rate (ORR)(Up to week 52)
- Overall Survival (OS)(Up to 2 years)
- Duration of Response(Up to 2 years)
- Absolute Change in the Percentage of CD8 Cells in Tumor Tissue From Baseline at Cycle 2.(At cycle 2 (each cycle is 28 days))