Sargramostim (GM-CSF) + PD-1

Metastatic Melanoma Clinical Trial

Official title:

Copy of A Phase II Trial of Pembrolizumab (Anti PD-1) Therapy Combined With Sargramostim (GM-CSF) in Unresectable or Metastatic Melanoma

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04703426
• Other study ID #: 20-370
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 16, 2021
• Est. completion date: June 9, 2025

Study information

• Verified date: May 2023
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

This is an open-label phase II study looking at safety and efficacy of the combination of pembrolizumab (PD-1 inhibition and sargramostim (GMCSF) in people with unresectable stage III or IV melanoma who may have received prior immunotherapy in the metastatic setting.

The U.S. Food and Drug Administration (FDA) has not approved sargramostim as a treatment option for people with stage III or IV melanoma The U.S. Food and Drug Administration (FDA) has approved pembrolizumab as a treatment option for people with stage III or IV melanoma who have received prior immunotherapy in the metastatic setting.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

Participants will receive the study drug(s) for as long as they do not have serious side effects and their disease does not get worse and will be followed for safety 30 days after the last dose of study drug(s). Participants may also be followed for long term follow-up every 12 weeks from the last dose of study drug(s).

It is expected that about 30 people will take part in this research study.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 9, 2025
• Est. primary completion date: June 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma
• Stage III Melanoma
• Stage IV Melanoma
• Unresectable Melanoma

Intervention

Drug:
• Sargramostim (GM-CSF)
Drug that binds to the protein PD-1 to help immune cells kill cancer cells better, it is given as an intravenous injection through a vein.
• Pembrolizumab (anti-PD-1)
Drug that stimulates blood cells that may help support the immune system during cancer treatment, given as intravenous infusion

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Partner Therapeutics (PTx)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	The primary study endpoint is response rate per RECIST criteria.	12 weeks
Secondary	Number of Participants With Treatment-Related Adverse Events	Number and proportion of adverse events, graded as defined by CTCAE version 5.0	12 weeks
Secondary	Overall Survival Rate	Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) will be used.	12 weeks
Secondary	Progression Free Survival Rate	Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) will be used.	12 weeks
Secondary	Overall Response Rate (ORR)-irRC	To evaluate the overall response rate in advanced melanoma to combination anti- PD-1 therapy and sargramostim by irRC criteria.	12 weeks
Secondary	CD4+ ICOS T cell changes	Evaluate changes in CD4+ ICOS T cells from biopsies (pre-treatment, on-treatment, post-treatment) and correlate using Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)	12 weeks