An Open-label, Single Center Study Evaluating the Safety and Efficacy of Roflumilast Foam 0.3% in Subjects With Cutaneous Adverse Events Due to Checkpoint Inhibitors

An Open-label, Single Center Study Evaluating the Safety and Efficacy of Roflumilast Foam 0.3% in Subjects With Cutaneous Adverse Events Due to Checkpoint Inhibitors

To assess the safety and efficacy of QD 0.3% topical roflumilast foam in patients with cutaneous adverse events due to checkpoint inhibitors over 16 weeks, with or without previous treatment.

Inclusion Criteria:

1. Male or female subjects aged 18 years or older.
2. Life expectancy ≥ 36 weeks.
3. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
4. Participants are legally competent to sign and give informed consent.
5. Patients receiving current or recent (within 6-months) treatment with immune checkpoint inhibitor(s).
6. Diagnosis of Immune Checkpoint Inhibitor-Related Toxicities Mild (G1 or <10%), Moderate (G2 or 10-30% BSA), Severe (G3 or 30+ % BSA) using CTCAE v5.0 with the following: Maculopapular rash, pruritus, bullous dermatitis, eczematous rashes, lichenoid eruption, or Psoriasis/Psoriasiform.
7. Agreement to NOT use topical and systemic corticosteroids for treatment of ICI-related toxicity during the study for first 2 weeks.
8. Agreement to not use systemic or biologic immunomodulating therapies during trial term unless cutaneous toxicity is not responding to Roflumilast therapy within the first 4 weeks and toxicity severity increases to high-grade (grade 3-4).
9. Agreement not to change the dose, form or type of antihistamines if on a stable dose for at least 1 month prior to baseline and not to initiate use of any new antihistamines during participation in the study.
10. Females of childbearing potential (FOCBP) must have a negative urine pregnancy test at Screening and Baseline/Day 1. In addition, sexually active FOCBP must agree to use at least one form of a highly effective or barrier method of contraception throughout the trial. The use of abstinence as a contraceptive measure is acceptable as long as this is a consistent part of a lifestyle choice and an acceptable backup method has been identified if the subject becomes sexually active.
11. Females of non-childbearing potential should either be post-menopausal with spontaneous amenorrhea for at least 12 months or have undergone surgical sterilization (permanent sterilization methods include hysterectomy, bilateral oophorectomy, hysteroscopic sterilization, bilateral tubal ligation or bilateral salpingectomy).
12. Subjects are considered reliable and capable of adhering to the Protocol and visit schedule, according to the judgment of the Investigator.

Exclusion Criteria:

1. Subjects who have pre-existing non-cutaneous toxicities requiring systemic immunosuppression.
2. Subjects who cannot discontinue medications and treatments prior to the Baseline visit and during the study according to Excluded Medications and Treatments (Table Excluded Medications and Treatments to be added).
3. Oral or colitis toxicities associated with immune checkpoint inhibitor therapy at time of study enrollment.
4. Subjects with any condition in the treatment area which, in the opinion of the Investigator, could confound efficacy measurements.
5. Subjects with known genetic dermatological conditions that overlap with cutaneous adverse events related to checkpoint inhibitor per investigator.
6. Subjects with moderate to severe liver impairment (Child-Pugh B or C).
7. Subjects with known allergies to excipients in Roflumilast foam (petrolatum, isopropyl palmitate, methylparaben, propylparaben, diethylene glycol monoethyl ether, hexylene glycol, cetylstearyl alcohol, dicetyl phosphase and ceteth-10 phosphate).
8. Subjects who cannot discontinue the use of systemic CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously for 2 weeks prior to Baseline/Day 1 and during the study period.
9. Subjects who have received oral roflumilast (Daxas®, Daliresp®) within 4 weeks prior to Baseline/ Day 1.
10. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding.
11. Previous treatment with Roflumilast cream or foam (any potency).
12. Subjects with a history of a major surgery (excluding minor biopsies) within 4 weeks prior to Baseline/Day 1 or subjects who have a major surgery planned during the study.
13. Subjects with a history of chronic alcohol or drug abuse within 6 months prior to Screening.
14. Subjects who are unable to communicate, read or understand the local language, or who display another condition, which in the Investigator's opinion, makes them unsuitable for clinical study participation.
15. Subjects who are family members of the clinical study site, clinical study staff, or sponsor.