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Trial record 4 of 7 for:    PF-04518600

Avelumab, Utomilumab, Anti-OX40 Antibody PF-04518600, and Radiation Therapy in Treating Patients With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT03217747
Recruitment Status : Recruiting
First Posted : July 14, 2017
Last Update Posted : October 30, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE July 12, 2017
First Posted Date  ICMJE July 14, 2017
Last Update Posted Date October 30, 2020
Actual Study Start Date  ICMJE August 2, 2017
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Incidence of adverse events [ Time Frame: Up to 1 year ]
    Will be graded per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Descriptive statistics will be provided on the grade and type of toxicity by dose level.
  • Evaluation of CD8 immune biomarkers assessed in tumor and blood biospecimens [ Time Frame: Up to 1 year ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 12, 2017)
  • Adverse Events of Different Treatment Combinations of Avelumab When Administered in Combination with Checkpoint Agonist(s) with or without Radiation, or Radiation and Cisplatin [ Time Frame: 56 days ]
    Adverse events (AEs) determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
  • Evaluation of CD8 Immune Biomarkers [ Time Frame: Baseline up to 12 weeks after study drug given ]
    Changes in CD8 expression analyzed before and after treatment using a paired t-test if the data are Normally distributed, and a Wilcoxon signed rank test if not.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Objective response rate [ Time Frame: Up to 1 year ]
    Will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and immune-related RECIST (irRECIST). A 95% confidence interval of response rate will be estimated based on a binomial distribution.
  • Progression-free survival [ Time Frame: From cycle 1 start date until the earliest date of disease progression, assessed up to 1 year ]
    Will be assessed per RECIST v1.1 and irRECIST.
  • Duration of response [ Time Frame: From time from earliest date of disease response until the earliest date of disease progression, assessed up to 1 year ]
    Will be assessed per RECIST v1.1 and irRECIST.
  • Overall survival [ Time Frame: From the cycle 1 start date until death due to any cause, assessed up to 1 year ]
  • Response data in irradiated and non-irradiated lesions [ Time Frame: Up to 1 year ]
  • Evaluation of various immune biomarkers from tumor and blood biospecimens [ Time Frame: Up to 1 year ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2017)
  • Objective Response Rate per RECIST v1.1 [ Time Frame: Baseline up to 12 weeks after study drug given ]
    Objective response rate determined by radiographic disease assessments per RECIST v1.1.
  • Objective Response Rate per irRECIST [ Time Frame: Baseline up to 12 weeks after study drug given ]
    Objective response rate determined by radiographic disease assessments per irRECIST.
  • Progression-free survival [ Time Frame: Start of study drugs up to 12 weeks after study drug given ]
    Progression-free survival defined as the time from Cycle 1 start date until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and irRECIST, or death due to any cause, if occurring sooner than progression.
  • Duration of response [ Time Frame: Start of study drugs up to 12 weeks after study drug given ]
    Duration of response determined by radiographic disease assessment, defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1 and irRECIST, or death due to any cause, if occurring sooner than progression.
  • Overall survival [ Time Frame: Start of study drugs up to 4 years after study drug given ]
    Overall survival determined from the Cycle 1 start date until death due to any cause.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Avelumab, Utomilumab, Anti-OX40 Antibody PF-04518600, and Radiation Therapy in Treating Patients With Advanced Malignancies
Official Title  ICMJE Phase I/II Study to Evaluate the Safety and Tolerability of Avelumab in Combination With Other Anti-Cancer Therapies in Patients With Advanced Malignancies
Brief Summary This phase I/II trial studies the side effects of avelumab when given in different combinations with utomilumab, anti-OX40 antibody PF-04518600, and radiation therapy in treating patients with malignancies that have spread to other places in the body. Immunotherapy with monoclonal antibodies, such as avelumab, utomilumab, and anti-OX40 antibody PF-04518600, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high-energy rays to kill tumor cells and shrink tumors. It is not yet known how well avelumab works in combination with these other anti-cancer therapies in patients with advanced malignancies.
Detailed Description

PRIMARY OBJECTIVES:

I. For Arms D-F, to establish the safety, tolerability, and dose-limiting toxicities (DLTs) of different treatment combinations of avelumab when administered in combination with checkpoint agonist(s) with or without radiation in patients with metastatic solid tumors in order to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D).

II. To correlate pre- and post-treatment CD8 expression with clinical benefit (complete response [CR], partial response [PR], or stable disease [SD] for > 6 months).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of the different treatment combinations in patients with metastatic solid tumors by assessing objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune-related RECIST (irRECIST).

II. To evaluate the efficacy of the different treatment combinations in patients with metastatic solid tumors by assessing progression-free survival (PFS), duration of response (DOR), and overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To understand the mechanism of action of the avelumab plus an immune modulator combination, as well as potential mechanisms of resistance.

II. To characterize the effect of avelumab combinations on immune biomarkers in peripheral blood and tumor tissue obtained from subjects pre- and post-treatment.

III. To compare the response in irradiated versus non-irradiated lesions in Arms D-F.

IV. To investigate immune biomarkers that are potentially predictive of response and resistance with the combination of avelumab and an immune modulator.

OUTLINE: Patients are assigned to 1 of 6 arms.

ARM A: Patients receive utomilumab intravenously (IV) over 60 minutes on day 1 of each cycle and avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive anti-OX40 antibody PF-04518600 IV over 60 minutes on days 1 and 15 of each cycle and avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive anti-OX40 antibody PF-04518600 IV over 60 minutes on days 1 and 15 of each cycle, utomilumab over 60 minutes on day 1, and avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM D: Patients undergo radiation therapy on days -14 to -1. Patients receive avelumab IV over 60 minutes on days 1 and 15 of beginning day 15 of cycle 1 and utomilumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM E: Patients undergo radiation therapy on days -14 to -1. Patients receive avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1 and anti-OX40 antibody PF-04518600 IV over 60 minutes on days 1 and 15, and. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM F: Patients undergo radiation therapy on days -14 to -1. Patients receive avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1, utomilumab IV over 60 minutes on day 1, and anti-OX40 antibody PF-04518600 IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients will be followed up at 30 days and then every 12 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Malignant Solid Neoplasm
  • Castration-Resistant Prostate Carcinoma
  • Malignant Neoplasm
  • Malignant Solid Neoplasm
  • Metastatic Malignant Solid Neoplasm
  • Metastatic Prostate Carcinoma
  • Prostate Carcinoma Metastatic in the Bone
  • Refractory Malignant Solid Neoplasm
  • Stage IV Prostate Cancer AJCC v8
  • Stage IVA Prostate Cancer AJCC v8
  • Stage IVB Prostate Cancer AJCC v8
Intervention  ICMJE
  • Biological: Anti-OX40 Antibody PF-04518600
    Given IV
    Other Name: PF-04518600
  • Drug: Avelumab
    Given IV
    Other Names:
    • Bavencio
    • MSB-0010718C
    • MSB0010718C
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
    • Cancer Radiotherapy
    • Irradiate
    • Irradiated
    • irradiation
    • Radiation
    • Radiotherapeutics
    • RADIOTHERAPY
    • RT
    • Therapy, Radiation
  • Biological: Utomilumab
    Given IV
    Other Names:
    • PF 05082566
    • PF 5082566
    • PF-05082566
    • PF-2566
Study Arms  ICMJE
  • Experimental: Arm A (utomilumab, avelumab)
    Patients receive utomilumab IV over 60 minutes on day 1 of each cycle and avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Avelumab
    • Biological: Utomilumab
  • Experimental: Arm B (PF-04518600, avelumab)
    Patients receive anti-OX40 antibody PF-04518600 IV over 60 minutes on days 1 and 15 of each cycle and avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: Anti-OX40 Antibody PF-04518600
    • Drug: Avelumab
  • Experimental: Arm C (PF-04518600, utomilumab, avelumab)
    Patients receive anti-OX40 antibody PF-04518600 IV over 60 minutes on days 1 and 15 of each cycle, utomilumab over 60 minutes on day 1, and avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: Anti-OX40 Antibody PF-04518600
    • Drug: Avelumab
    • Biological: Utomilumab
  • Experimental: Arm D (avelumab, utomilumab, radiation therapy)
    Patients undergo radiation therapy on days -14 to -1. Patients receive avelumab IV over 60 minutes on days 1 and 15 of beginning day 15 of cycle 1 and utomilumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Avelumab
    • Radiation: Radiation Therapy
    • Biological: Utomilumab
  • Experimental: Arm E (avelumab, PF-04518600, radiation therapy)
    Patients undergo radiation therapy on days -14 to -1. Patients receive avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1 and anti-OX40 antibody PF-04518600 IV over 60 minutes on days 1 and 15, and. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: Anti-OX40 Antibody PF-04518600
    • Drug: Avelumab
    • Radiation: Radiation Therapy
  • Experimental: Arm F (avelumab, PF-04518600, radiation therapy)
    Patients undergo radiation therapy on days -14 to -1. Patients receive avelumab IV over 60 minutes on days 1 and 15 beginning day 15 of cycle 1, utomilumab IV over 60 minutes on day 1, and anti-OX40 antibody PF-04518600 IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: Anti-OX40 Antibody PF-04518600
    • Drug: Avelumab
    • Radiation: Radiation Therapy
    • Biological: Utomilumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 29, 2019)
184
Original Estimated Enrollment  ICMJE
 (submitted: July 12, 2017)
188
Estimated Study Completion Date  ICMJE September 30, 2023
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects must be refractory to, or intolerant of, established therapy known to provide clinical benefit for their conditions, or where subjects refuse existing therapies.
  • Subjects must have measurable disease (RECIST v 1.1) or patients may have bone metastatic disease evaluable by Prostate Cancer Working Group 2 (PCWG2) for subjects with metastatic castration-resistant prostate cancer (CRPC) or according to tumor evaluation criteria best suitable and accepted for the tumor type evaluated.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Platelets >= 100 x 10^9/L (For patients with hepatocellular carcinoma, platelets >= 70 x 10^9/L).
  • Hemoglobin >= 9 g/dL.
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L.
  • White blood cell (WBC) >= 3 x 10^9/L.
  • Subjects must be transfusion independent (i.e., no blood product transfusions for a period of at least 14 days prior to cycle 1 day 1 [start of study treatment]).
  • Alanine transaminase (ALT) =< 2.5 x upper normal limit (ULN) (=< 5 x ULN for subjects with documented metastatic disease to the liver).
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with documented metastatic disease to the liver).
  • Alkaline phosphatase < 4 x ULN.
  • Total bilirubin =< 1.5 x ULN (In the expansion cohort, subjects with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of =< 3 x ULN).
  • Albumin >= 3 g/dL.
  • Serum creatinine =< 2 x upper limit of normal (ULN) or estimated creatinine clearance >= 30 ml/min as calculated using the Cockcroft-Gault formula.
  • Subject has recovered to grade =< 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 (NCI-CTCAE v 4.03) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia. The exceptions for such effects are allowed lab values of =< grade 2 specified elsewhere in these inclusion criteria.
  • Life expectancy of at least 12 weeks.
  • Negative serum pregnancy test in women of childbearing potential within 7 days of first dose of treatment and patients of child-bearing potential must agree to use effective contraception during and after 90 days post dose. A woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant. This includes women on oral, injectable or mechanical contraception; women who are single and women whose male sexual partners have been vasectomized or whose male sexual partners have received or are utilizing mechanical contraceptive devices.
  • Subjects must have biopsiable disease. For Arms A, B, and C, subjects must have at least two lesions amenable to biopsy and response evaluation. For Arms D, E, and F, subjects should have at least three lesions amenable to biopsy, response evaluation, and radiation. Tumor lesions used for biopsy should not be lesions used as RECIST target lesions. However, if patients in Arms D, E, and F do not have three separate lesions, patients will be eligible if there are two lesions, in which one is > 2 centimeters (short axis) and can be used for both biopsy and response evaluation.
  • Subjects must give informed consent according to the rules and regulations of the individual participating sites.

Exclusion Criteria:

  • Subjects with primary central nervous system (CNS) tumor or CNS tumor involvement. However, subjects with metastatic CNS tumors may participate in this study if the subject is: > 4 weeks from prior therapy completion (including radiation and/or surgery); clinically stable with respect to the CNS tumor at the time of study entry; not receiving steroid therapy in treating CNS tumor or CNS tumor involvement; not receiving anti-convulsive medications (that were started for brain metastases).
  • Major surgery, radiation therapy or systemic anti-cancer therapy within 4 weeks of study drug administration (6 weeks for mitomycin C or nitrosoureas). Palliative radiotherapy to a limited field is allowed after consultation with the medical monitor at any time during study participation, including during screening, unless it's clearly indicative of disease progression.
  • Subjects with prior anti-PD-1, anti-PD-L1 treatment. For Arms A and D, subjects may not have had prior 4-1BB treatment. For Arms B and E, subjects may not have had prior OX40 treatment. For Arms C and F, subjects may not have had prior 4-1BB or OX40 treatment.
  • Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated).
  • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association classification class II), or serious cardiac arrhythmia requiring medication.
  • Active infection requiring systemic therapy.
  • Treatment with an investigational anti-cancer study drug within 4 weeks prior to study drug administration date.
  • Concurrent therapy with approved or investigational anticancer therapeutics.
  • Known prior severe hypersensitivity to investigational product(s) or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v 4.03 grade >= 3).
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent; c. steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication).
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
  • Prior organ transplantation including allogenic stem-cell transplantation.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV ribonucleic acid (RNA) if anti-HCV antibody screening test positive).
  • Vaccination (live attenuated virus) within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines.
  • Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however, alopecia, sensory neuropathy grade =< 2, or other grade =< 2 not constituting a safety risk based on investigator's judgment are acceptable.
  • Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
  • Pregnancy or lactation.
  • Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 90 days after the end of study treatment. Women of child-bearing potential is defined as sexually mature women who are not surgically sterile or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months).
  • A diagnosis of active scleroderma, lupus, or other rheumatologic disease which in the opinion of the treating radiation oncologist precludes safe radiation therapy.
  • Has had prior radiation therapy within the past 3 months where the high dose area of the prior radiation would overlap with the high dose area of the intended radiation based on the judgement of the treatment oncologist.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Aung Naing, MD 713-563-1930 anaing@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03217747
Other Study ID Numbers  ICMJE 2017-0014
NCI-2018-01118 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0014 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Aung Naing M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP