Pembrolizumab and GM-CSF in Biliary Cancer

NCT02703714 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 154524NCI-2017-01372R03CA212877
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label phase II trial to examine efficacy and safety of a novel combination of pembrolizumab plus induction GM-CSF in patients with advanced biliary cancers treated at University of California, San Francisco (UCSF). This phase II study will examine the efficacy and safety of the novel combination of pembrolizumab plus induction GM-CSF in advanced biliary cancer patients with the hypotheses that the combination may increase proportion of patients with overall response compared to contemporary historical controls, with acceptable safety.

Conditions

Biliary Cancer

Keywords

Advanced; Locally-advanced; Not eligible for resection; Prior chemotherapy treatment

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Proportion of subjects with measurable disease at study entry who obtained either a complete response (CR) or partial response (PR) (confirmed + unconfirmed) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at any time during the course of treatment.

  Up to 2 years

Secondary Outcomes (9)

• Proportion of Participants With Treatment-related AEs

  During study treatment and for 30 days after last dose or until start of new treatment (up to 2 years)

• Proportion of Participants With PD-L1 Positive Status

  Up to 4 years

• Proportion of Participants With Progression-Free Survival (PFS) at 6 Months

  6 months after start of study treatment

• Median Duration of Response

  Within 4 years after start of study treatment

• Median Duration of Response Stratified by Sub-type of Biliary Cancer

  Within 4 years after start of study treatment

Study Arms (1)

Pembrolizumab and GM-CSF

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive sargramostim subcutaneous injection (SC) on days 1-14 of courses 1-2 or 2-3. Treatment repeats every 21 days for up to 2 courses for sargramostim and for up to 35 courses (24 months) for pembrolizumab in the absence of disease or unaccepted toxicity.

Drug: Pembrolizumab; Drug: Sargramostim

Interventions

Pembrolizumab DRUG

200 mg given intravenously (IV)

Also known as: MK-3475, Keytruda

Pembrolizumab and GM-CSF

Sargramostim DRUG

250 µg given subcutaneously (SC)

Also known as: GM-CSF

Pembrolizumab and GM-CSF

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Demonstrate adequate organ function
• Absolute neutrophil count (ANC) \>= 1,000/microliter (mcL)(performed within 28 days of treatment initiation)
• Platelets \>= 60,000/mcL (\>= 75,000/mcL in expansion cohort) (performed within 28 days of treatment initiation)
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 28 days of treatment initiation)
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (performed within 28 days of treatment initiation)
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (performed within 28 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 5 X ULN (performed within 28 days of treatment initiation)
• Albumin \>= 2.5 mg/dL (performed within 28 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as prothrombin time (PT) or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation)
• Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 28 days of treatment initiation)
• Patients with known hepatitis B (HBV) or hepatitis C virus (HCV) infection are eligible provided liver function parameters meet laboratory eligibility criteria
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated and received study therapy in a study of an investigational agent, or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy for purposes of immunosuppression or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active Bacillus Tuberculosis (TB).
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has untreated active Hepatitis B (e.g., HBsAg reactive).
• Has an active infection requiring systemic antibiotic therapy at time of enrollment.
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has received treatment with an anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has received treatment with chemotherapy, targeted small molecule therapy, or radiation therapy to non-liver sites within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent administered more than 2 weeks earlier.
• Has had prior chemoembolization, bland embolization, radioembolization, local ablative therapies, radiation to liver tumors, or major surgery such as liver resection within 4 weeks prior to study enrollment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to intervention more than 4 weeks earlier.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of or any evidence of active, non-infectious pneumonitis.
• Has had prior liver or other organ transplantation.

Sponsors & Collaborators

• Robin Kate Kelley: lead
• American Society of Clinical Oncology: collaborator
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94158, United States

Location

Related Publications (1)

• Keenan BP, McCarthy EE, Ilano A, Yang H, Zhang L, Allaire K, Fan Z, Li T, Lee DS, Sun Y, Cheung A, Luong D, Chang H, Chen B, Marquez J, Sheldon B, Kelley RK, Ye CJ, Fong L. Circulating monocytes associated with anti-PD-1 resistance in human biliary cancer induce T cell paralysis. Cell Rep. 2022 Sep 20;40(12):111384. doi: 10.1016/j.celrep.2022.111384.

  PMID: 36130508 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

pembrolizumab; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System 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

Results Point of Contact

• Title: Dr. R. Katie Kelley, MD
• Organization: University of California, San Francisco

katie.kelley@ucsf.edu

(415) 353-9888

Study Officials

• R. Kate Kelley, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 4, 2016
• First Posted: March 9, 2016
• Study Start: May 6, 2016
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: January 25, 2022
• Results First Posted: January 12, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)