Testing the PD-1 Antibody, MK3475, Given With Ziv-aflibercept in Patients With Advanced Cancer
A Phase 1 Trial of MK-3475 Plus Ziv-Aflibercept in Patients With Advanced Solid Tumors
6 other identifiers
interventional
59
2 countries
9
Brief Summary
This phase I trial studies the side effects and best dose of ziv-aflibercept when given together with pembrolizumab in treating patients with solid tumors that that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Ziv-afibercept works by decreasing blood and nutrient supply to the tumor, which may result in shrinking the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ziv-aflibercept together with pembrolizumab may be a better treatment for patients with advanced solid tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2015
Longer than P75 for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 21, 2014
CompletedFirst Posted
Study publicly available on registry
November 24, 2014
CompletedStudy Start
First participant enrolled
April 8, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 21, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 20, 2027
ExpectedMay 13, 2026
January 1, 2026
10.1 years
November 21, 2014
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Recommended combination dose of ziv-aflibercept and pembrolizumab
Will be assessed by dose-limiting toxicities. Safety will be evaluated for all treated patients using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. All adverse events recorded during the trial will be summarized and presented by dose level. For patients enrolled in the dose expansion phase of the trial, adverse events summaries will also be summarized according to disease cohort. The proportion of patients with grade-3 or higher adverse events will be presented with 90% exact binomial confidence interval.
4 weeks
Secondary Outcomes (4)
Objective response rate (ORR)
Between the date of first dose of trial therapy and the date of objectively documented disease progression or cessation of trial therapy, whichever occurs first, assessed up to 12 weeks
Progression-free survival
Time from start of trial treatment until objective disease progression (per RECIST) or death, whichever occurs first, assessed up to 6 months
Overall survival
Time from start of trial treatment to death from any cause, assessed up to 12 months
Time-to-progression
Time interval between the dates of the start of trial treatment and first documentation of progressive disease, assessed up to 12 weeks
Other Outcomes (5)
Phenotype changes in cell populations
Baseline to up to 12 weeks
Tie-2 expressing monocytes
Up to 12 weeks
Changes in antigen specific responses to known melanoma antigen epitopes (melanoma antigen recognized by T cells 1, NY-ESO-1)
Baseline to up to 12 weeks
- +2 more other outcomes
Study Arms (1)
Treatment (pembrolizumab and ziv-aflibercept)
EXPERIMENTALPatients receive pembrolizumab intravenously (IV) over approximately 30 minutes and ziv-aflibercept IV over 1-2 hours on day 1. Cycles repeat every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, blood sample collection and tumor biopsy throughout the study.
Interventions
Given IV
Given IV
Undergo tumor biopsy
Undergo blood sample collection
Undergo MRI
Undergo CT scan
Eligibility Criteria
You may qualify if:
- In dose escalation, patients must have histologically or cytologically confirmed metastatic disease from any solid tumor (NOS 10029000). In dose expansion part 1, patients must have histologically or cytologically confirmed metastatic melanoma (10053571), renal cell carcinoma (NOS 10038485), ovarian cancer (NOS 10033272), or colorectal cancer (10009951,10038045). In dose expansion part 2, patients must have PD-1 resistant melanoma (10053571), PD-1 resistant renal cancer (NOS 10038485), or sarcoma (10061271)
- Renal cell patients must have had at least one prior vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI)
- Ovarian cancer patients must be resistant to platinum therapy; therapy (i.e. within 6 months of last platinum therapy); patients who received greater than two prior platinum containing regimens will not be eligible
- Patients with colorectal cancer should have failed at least one oxaliplatin-containing regimen
- No more than two prior therapies for metastatic disease
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of MK-3475 in combination with ziv-aflibercept in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
- Estimated life expectancy of greater than 6 months
- Leukocytes \>= 2,000/mcL (within 10 days of treatment initiation)
- Absolute neutrophil count \>= 1,500/mcL (within 10 days of treatment initiation)
- Platelets \>= 100,000/mcL (within 10 days of treatment initiation)
- Hemoglobin \>= 9 g/dL OR \>= 5.6 mmol/L (within 10 days of treatment initiation)
- Serum total bilirubin =\< 1.5 X upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 ULN (within 10 days of treatment initiation)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional ULN OR =\< 5 X ULN for patients with liver metastases (within 10 days of treatment initiation)
- Serum creatinine =\< 1.5 X ULN or measured or calculated creatinine clearance (CrCl) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl); creatinine clearance should be calculated per institutional standard (within 10 days of treatment initiation)
- +12 more criteria
You may not qualify if:
- Patients who have had chemotherapy, targeted small molecule therapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Note: patients with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
- Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Patients who are currently participating in or have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events (AEs) due to agents administered 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, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
- Lesions suspected to be at higher-risk for bleeding such as bowel involvement with tumor that invades into the bowel wall or involves the intraluminal component of bowel by imaging or direct visualization or central pulmonary lesions
- Ulcerated skin lesions
- Full anti-coagulant therapy Coumadin; patients may be receiving therapeutic Lovenox, Fragmin, or other heparin product that does not require laboratory monitoring
- Poorly-controlled hypertension as defined blood pressure (BP) \> 150/100 mmHg, or systolic (S) BP \> 180 mmHg when diastolic (D) BP \< 90 mmHg, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment
- Pregnant or nursing women
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients with carcinomatous meningitis should also be excluded
- Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 3 months 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
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607, United States
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6, Canada
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Related Publications (2)
Baginska J, Nau A, Gomez Diaz I, Giobbie-Hurder A, Weirather J, Vergara J, Abrecht C, Hallisey M, Dennis J, Severgnini M, Huezo J, Marciello I, Rahma O, Manos M, Brohl AS, Bedard PL, Renouf DJ, Sharon E, Streicher H, Ott PA, Buchbinder EI, Hodi FS. Ziv-aflibercept plus pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment. Cancer Immunol Immunother. 2024 Jan 18;73(1):17. doi: 10.1007/s00262-023-03593-2.
PMID: 38236249DERIVEDRahma OE, Tyan K, Giobbie-Hurder A, Brohl AS, Bedard PL, Renouf DJ, Sharon E, Streicher H, Hathaway E, Cunningham R, Manos M, Severgnini M, Rodig S, Stephen Hodi F. Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors. J Immunother Cancer. 2022 Mar;10(3):e003569. doi: 10.1136/jitc-2021-003569.
PMID: 35264434DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Frank S Hodi
Dana-Farber - Harvard Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 21, 2014
First Posted
November 24, 2014
Study Start
April 8, 2015
Primary Completion
May 21, 2025
Study Completion (Estimated)
January 20, 2027
Last Updated
May 13, 2026
Record last verified: 2026-01