Fiber-Boost Randomized Controlled Trial

The activity of immune checkpoint blockade (ICB) mechanistically depends on the host microbiome and is manipulable through diet. In this study termed Fiber-Boost, we propose a multicenter trial of a supplement-based high-fiber diet (HFD) in non-small cell lung cancer (NSCLC) treated with first-line ICB monotherapy. Using a randomized, controlled design, we mechanistically explore the role of dietary fibers in cancer immunotherapy. Circulating tumor DNA (ctDNA) quantification as well as a rich pipeline of companion microbiome and immune profiling technologies will improve the understanding of the diet-microbiome-immune axis in therapeutic anticancer immunity and treatment response. The overarching goal is to elucidate novel therapeutic strategies for ICB sensitization in NSCLC using microbiome-centered, non-pharmaceutical interventions. Sex and gender dimensions are biologically not sufficiently relevant for the current study to merit corresponding stratification or analyses.

Inclusion criteria

• Age ≥18 years
• Written informed consent according to Swiss law and ICH/GCP regulations before inclusion and prior to any trial-specific procedures
• Histologically or cytologically confirmed NSCLC
• Advanced or recurrent NSCLC not amenable to curative treatment
• PD-L1 expression ≥50% (TPS) determined by an approved IHC test
• No actionable genetic alterations in genes such as EGFR, ALK, ROS1, HER2, BRAF, RET, MET, NTRK
• First-line palliative PD-1/PD-L1-targeted monotherapy at a 3-weekly schedule indicated per local investigator
• Willingness and ability to undergo study interventions
• ECOG performance status 0-2
• Adequate organ function:
• Hemoglobin ≥70 g/L, platelet count ≥50 G/L, granulocytes ≥1 G/L
• Bilirubin, ALT, AST ≤3 x ULN
• Glomerular filtration rate (Cockroft-Gault) ≥30 mL/min/1.73m²
• Measurable or evaluable disease per RECIST 1.1
• Patients with CNS metastases are eligible, provided there is no requirement for corticosteroids as therapy for CNS disease and no evidence of clinical progression
• Women with child-bearing potential use effective contraception (two independent methods), are not currently pregnant or lactating, and agree to not become pregnant during the trial treatment and during 3 months thereafter. A negative pregnancy test in either urine or blood is required for women with child-bearing potential before trial inclusion.
• Men who are not sterile agree to use contraceptive methods (condoms) or abstain from sexual intercourse during the trial treatment and 3 months thereafter.

Exclusion criteria

-History of malignancy, unless in remission for at least 3 years before inclusion with the exception of pT1-2 prostate cancer Gleason score <6, adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer

Adjuvant or additive systemic ICB treatment within 6 months prior to inclusion

• Systemic treatment with an antibiotic within 10 days of ICB treatment/HFD intervention start
• Concomitant immunosuppressive drugs including corticosteroids at a daily dose of ≥10mg prednisone equivalents, methotrexate, azathioprine, TNF-α inhibitors
• Concurrent treatment with other experimental drugs or other anticancer therapy
• Major surgical procedures within 14 days prior to inclusion as judged by the investigator
• Active autoimmune disease requiring systemic immunosuppressive treatment that is seen as contraindication for the use of PD-1/PD-L1-targeted monoclonal antibodies
• Uncontrolled diabetes mellitus
• Severe or uncontrolled cardiovascular disease
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications
• Had an allogeneic tissue/solid organ transplant
• Ongoing supplementation with OptiFibre® or another fiber supplement