High-Intensity Exercise and High-Fiber Diet for Immunotherapy Outcomes in Melanoma Patients: The DUO Trial

Inclusion Criteria:

• Age ≥18 years; due to the rarity of the disease in those <18 years, this age bracketwill not be included.

• Histologically diagnosed with advanced melanoma.

• Having been or newly receiving immune checkpoint inhibitor, including anti-PD1,antiCTLA4, and/or anti-LAG3 monoclonal antibodies, with palliative intent for atleast one month with a plan to continue immunotherapy for at least 8 weeks (i.e.,study intervention period) at the time of recruitment.

• Not receiving other concurrent tumor-directed systemic treatment (e.g., chemotherapyor targeted therapy).

• Medically cleared to participate in high-intensity exercise and high-fiber diet bytheir treating oncologist.

• Not having medical conditions that could exacerbate with exercise, such as bonedisease at imminent risk of fracture or uncontrolled cardiopulmonary or metabolicdiseases (e.g., uncontrolled hypertension or diabetes).

• Currently not meeting the physical activity guideline (i.e., more than 150 minutesper week of moderate-to-vigorous intensity, regular, structured aerobic exercise)over the past month at the time of recruitment.

• Currently not meeting the daily dietary fiber intake guideline (i.e., 30 grams/day)over the past month at the time of recruitment.

• Ability to communicate and complete written forms in English.

• Ability to understand and the willingness to sign informed consent prior to anystudy- related procedures.

• Willing to travel to DFCI for necessary data collection.

Exclusion Criteria:

• Receiving other concurrent systemic treatment for advanced melanoma such aschemotherapy or targeted therapy. This study is to exclusively target patientsreceiving immune checkpoint inhibitors where other treatments may impact the studyoutcomes of intervention efficacies and feasibilities.

• Participating in more than 150 minutes of moderate-to-vigorous aerobic exercise perweek over the past month. This study targets insufficiently active persons to assessthe effect of the described exercise intervention, where additional exercise doneregularly will contaminate the intervention outcomes.

• Consuming more than 25 and 38 grams of dietary fiber per day for women and men,respectively over the past month. This study targets persons who insufficiently takedietary fiber to assess the effect of the described dietary intervention, whereadditional dietary fiber intake will contaminate the intervention outcomes.

• Having unstable comorbidities or medical conditions that prevent participation inhigh intensity exercise or high-fiber diet interventions. Patients with unstablemedical conditions may develop unexpected adverse events from exercise and dietarychanges. For the purpose of patients' safety, patients with unstable medicalconditions are excluded.

• Subjects who in the opinion of the investigator may not be able to comply with thesafety monitoring requirements of the study.

• Development of second malignancy (except for basal cell carcinoma or squamous cellcarcinoma of the skin) that requires concurrent treatment, which would interferewith this study.