Diphencyprone Plus Immune Checkpoint Inhibition in the Treatment of Cutaneous Metastases

A Phase I, Open Label Study Employing the Topical Immunomodulator Diphencyprone to Improve Efficacy of PD-1 or PD-L1 Immune Checkpoint Inhibition in the Treatment of Advanced Cancer With Cutaneous Metastases

This is a phase I, open label study employing diphencyprone (DPCP) to characterize gene expression changes of various immune cell and tumor markers in cutaneous metastases treated with topical DPCP twice weekly for 12 weeks in combination with PD-1 or PD-L1 immune checkpoint inhibition (ICI), compared to pre-treatment cutaneous metastases and to describe the adverse events associated with DPCP when administered topically twice weekly for 12 weeks in combination with PD-1 or PD-L1 ICI.

Inclusion Criteria:

• Clinically diagnosed cancer with at least three cutaneous metastasis sites that are able to be biopsied.

• Subject's oncologist plans as next standard of care treatment to use an FDA- approved PD-1 or PD-L1 ICI therapy. In other words, the subject would be treated with PD-1 or PD-L1 ICI therapy even if not taking part in this study. Subjects can be either ICI-naïve (never having received ICI previously), or may have progressed/relapsed during ICI therapy, but the treating oncologist has elected to continue PD-1 or PD-L1 ICI therapy.

• Age ≥ 18 years.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately:

• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Subjects may not be receiving any other investigational agents.
• Subjects must not be receiving combination ICI, such as a PD-1 inhibitor with a CTLA-4 inhibitor.
• Subjects taking any of the following systemic therapies: corticosteroids, immunosuppressants, and/or any other medications (systemic or topical) that may affect the outcome of the study in the opinion of the investigator
• Subjects with any underlying diseases or dermatological conditions of the affected areas that require the use of interfering topical or systemic therapy, or that may, in the opinion of the investigator, impair immune responses such as HIV or lymphadenectomy of the axillary lymph node basin that drains the skin where DPCP is to be applied.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to DPCP, or any of the other components of the DPCP ointment formulation.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.