A Phase II trial of pembrolizumab (anti PD-1) therapy combined with sargramostim (GM-CSF) in Unresectable or Metastatic melanoma which has previously been treated with immune checkpoint inhibition

NOT ENROLLING
Protocol # :
20-370
Conditions
Unresectable Melanoma
Metastatic Melanoma
Stage III Melanoma
Stage IV Melanoma
Phase
II
Disease Sites
Melanoma, Skin
Principal Investigator
Buchbinder, Elizabeth, I
Site Research Nurses
Gormley, Jill, Kathleen
Livengood, Amanda

Trial Description

This research study is testing the combination of two drugs, sargramostim and pembrolizumab.
The study is designed to see if the combination of these study drugs would improve the
control of unresectable or metastatic melanoma cancer when compared to use of these drugs
alone.

The names of the study drugs involved in this study are:

- Pembrolizumab

- Sargramostim (GM-CSF)

Eligibility Requirements

Inclusion Criteria:

- Histologic or cytologic diagnosis of metastatic or unresectable stage III or IV
cutaneous melanoma

- Prior treatment with immunotherapy

- Age ≥ 18 years.

- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

- Participants must have normal organ and marrow function as defined below:

- leukocytes ≥3,000/mcL

- absolute neutrophil count ≥1,500/mcL

- platelets ≥100,000/mcL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

- creatinine within normal institutional limits OR creatinine clearance ≥60
mL/min/1.73 m2 for participants with creatinine levels above institutional
normal.

- Measurable disease (by CT, PET/CT or MRI)

- The effects of GMCSF and PD-1 inhibition on the developing human fetus are unknown.

For this reason women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in this study, she should
inform her treating physician immediately. Men treated or enrolled on this protocol must
also agree to use adequate contraception prior to the study, for the duration of study
participation, and 7 months after completion of study drug administration.

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

Exclusion Criteria:

- Participants who have had chemotherapy or radiotherapy within 4 weeks prior to
entering the study or those who have not recovered from adverse events due to agents
administered more than 4 weeks earlier.

- Participants who are receiving any other investigational agents.

- Participants with known brain metastases must have documented stability over a four
week interval and not be requiring active treatment for these. Prior radiation,
surgery and stereotactic radiosurgery are allowed but must be completed four weeks
prior to initiating therapy.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to Pembrolizumab or sargramostim.

- Need for systemic steroids at the time of enrollment. Physiologic replacement at a
dose of less than 10mg daily prednisone equivalent is allowed.

- 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.

- Participants who are considered Women of Child-Bearing Potential (WOCBP) must have a
negative serum pregnancy test in order to be eligible. Pregnant women are excluded
from this study because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with Pembrolizumab, breastfeeding
should be discontinued if the mother is treated with Pembrolizumab. These potential
risks may also apply to other agents used in this study.

- Known active HIV, Hepatitis B or Hepatitis C patients. HIV-positive participants on
combination antiretroviral therapy are ineligible because of the potential for an
immunologic effect with the therapy. Appropriate studies will be undertaken in
participants receiving combination antiretroviral therapy when indicated.

- Autoimmune disease that requires treatment at the time of enrollment.

20-370