Sargramostim (GM-CSF) + PD-1

NCT04703426 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 20-370
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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)

Conditions

Unresectable Melanoma; Metastatic Melanoma; Stage III Melanoma; Stage IV Melanoma

Keywords

Unresectable Melanoma; Metastatic Melanoma; Stage III Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The primary study endpoint is response rate per RECIST criteria.

  12 weeks

Secondary Outcomes (5)

• Number of Participants With Treatment-Related Adverse Events

  12 weeks

• Overall Survival Rate

  12 weeks

• Progression Free Survival Rate

  12 weeks

• Overall Response Rate (ORR)-irRC

  12 weeks

• CD4+ ICOS T cell changes

  12 weeks

Study Arms (1)

Sargramostim (GM-CSF) + Pembrolizumab (anti-PD-1)

EXPERIMENTAL

Participants will receive 12 weeks of sargramostim (GM-CSF) and pembrolizumab (anti-PD-1). Participants may be pre-medicated with drugs to reduce the chance of having a sensitivity reaction to the study treatment of pembrolizumab (anti-PD-1) and sargramostim (GM-CSF). Study cycles are 21 days in length: * Pembrolizumab (anti-PD-1) will be given by intravenous infusion once on day 1 of every 21 day cycle * Sargramostim (GM-CSF) will be self-administered by participants via a subcutaneous (below the skin) injection daily for days 1 - 14 of each 21- day cycle. Participants will be assessed at 12 weeks for disease response/progression and further study treatment.

Drug: Sargramostim (GM-CSF); Drug: Pembrolizumab (anti-PD-1)

Interventions

Sargramostim (GM-CSF) DRUG

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.

Also known as: Leukine

Sargramostim (GM-CSF) + Pembrolizumab (anti-PD-1)

Pembrolizumab (anti-PD-1) DRUG

Drug that stimulates blood cells that may help support the immune system during cancer treatment, given as intravenous infusion

Also known as: Keytruda

Sargramostim (GM-CSF) + Pembrolizumab (anti-PD-1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Partner Therapeutics (PTx): collaborator

MeSH Terms

Conditions

Melanoma

Interventions

sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Elizabeth Buchbinder, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 11, 2021
• Study Start: April 16, 2021
• Primary Completion: June 10, 2024
• Study Completion: June 9, 2025
• Last Updated: May 22, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu