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

NCT03217747 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 2017-0014NCI-2018-01118
• Study Type: interventional
• Target: 173
• Locations: 1 country
• Sites: 1

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 (advanced). 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.

Conditions

Advanced Malignant Solid Neoplasm; Castration-Resistant Prostate Carcinoma; 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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose-limiting Toxicities (DLTs) (All Will be Graded According to CTCAEv4.03 Criteria)

  DLTs were adverse events (AEs) related to study drug in the first 2 cycles and fulfilled one of the following * Discontinuation due to drug and/or XRT-related toxicity before DLT period ends * Delay \>28 days in receiving the next cycle due to drug and/or XRT-related toxicity * Hematologic * Gr4 neutropenia ≥7 days * Febrile neutropenia * Gr ≥3 thrombocytopenia associated with bleeding, or Gr 4 thrombocytopenia * Gr 4 anemia * Non-hematologic * Gr ≥3 nausea/vomiting or diarrhea ≥72 hours despite optimal supportive medications * Gr ≥3 fatigue ≥7 days * Gr≥2 pneumonitis ≥7 days despite corticosteroids * Gr≥3 rash ≥7 days despite treatment * Gr≥3 immune related toxicities ≥7 days despite corticosteroids * Any other Gr≥3 non-hematological toxicity (except for asymptomatic electrolytes abnormalities or hair loss which is not dose-limiting) * Gr≥3 AST, ALT, or total bilirubin elevation ≥7 days. Delay of treatment \> 14 days due to non-hematologic toxicity

  DLT was assessed during the first 2 cycles or 8 weeks (56 days) since C1D1 of treatment.

Secondary Outcomes (6)

• Objective Response Rate Per RECIST v1.1

  At baseline and at 8-week intervals (± 7 days). Confirmatory scans were obtained 4-8 weeks following initial objective response. After 1 year of treatment scans at 12-week intervals (± 7 days), independent of cycle delays, assessed upto 3 years.

• Objective Response Rate Per irRECIST

  At baseline and at 8-week intervals (± 7 days). Confirmatory scans were obtained 4-8 weeks following initial objective response. After 1 year of treatment scans at 12-week intervals (± 7 days), independent of cycle delays, assessed upto 3 years.

• Clinical Benefit Rate Per RECIST v1.1

  At baseline and at 8-week intervals (± 7 days). Confirmatory scans were obtained 4-8 weeks following initial objective response. After 1 year of treatment scans at 12-week intervals (± 7 days), independent of cycle delays, assessed upto 3 years.

• Clinical Benefit Rate Per irRECIST

  At baseline and at 8-week intervals (± 7 days). Confirmatory scans were obtained 4-8 weeks following initial objective response. After 1 year of treatment scans at 12-week intervals (± 7 days), independent of cycle delays, assessed upto 3 years.

• Disease Control Rate Per RECIST v1.1

  At baseline and at 8-week intervals (± 7 days). Confirmatory scans were obtained 4-8 weeks following initial objective response. After 1 year of treatment scans at 12-week intervals (± 7 days), independent of cycle delays, assessed upto 3 years.

Study Arms (6)

Arm A (utomilumab, avelumab)

EXPERIMENTAL

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.

Drug: Avelumab; Biological: Utomilumab

Arm B (PF-04518600, avelumab)

EXPERIMENTAL

Patients receive anti-OX40 agonist monoclonal 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.

Drug: Avelumab; Biological: Ivuxolimab

Arm C (PF-04518600, utomilumab, avelumab)

EXPERIMENTAL

Patients receive anti-OX40 agonist monoclonal 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.

Drug: Avelumab; Biological: Ivuxolimab; Biological: Utomilumab

Arm D (avelumab, utomilumab, radiation therapy)

EXPERIMENTAL

Patients undergo radiation therapy on days -5 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.

Drug: Avelumab; Radiation: Radiation Therapy; Biological: Utomilumab

Arm E (avelumab, PF-04518600, radiation therapy)

EXPERIMENTAL

DISCONTINUED AS OF AMENDMENT 9 (02/11/2020) 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 agonist monoclonal 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.

Drug: Avelumab; Biological: Ivuxolimab; Radiation: Radiation Therapy

Arm F (avelumab, PF-04518600, radiation therapy)

EXPERIMENTAL

DISCONTINUED AS OF AMENDMENT 9 (02/11/2020) 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 agonist monoclonal antibody PF-04518600 IV on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Avelumab; Biological: Ivuxolimab; Radiation: Radiation Therapy; Biological: Utomilumab

Interventions

Avelumab DRUG

Given IV

Also known as: Bavencio, MSB-0010718C, MSB0010718C

Arm A (utomilumab, avelumab); Arm B (PF-04518600, avelumab); Arm C (PF-04518600, utomilumab, avelumab); Arm D (avelumab, utomilumab, radiation therapy); Arm E (avelumab, PF-04518600, radiation therapy); Arm F (avelumab, PF-04518600, radiation therapy)

Ivuxolimab BIOLOGICAL

Given IV

Also known as: Anti-OX40 Agonist Monoclonal Antibody PF-04518600, PF-04518600, PF-8600, PF04518600

Arm B (PF-04518600, avelumab); Arm C (PF-04518600, utomilumab, avelumab); Arm E (avelumab, PF-04518600, radiation therapy); Arm F (avelumab, PF-04518600, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm D (avelumab, utomilumab, radiation therapy); Arm E (avelumab, PF-04518600, radiation therapy); Arm F (avelumab, PF-04518600, radiation therapy)

Utomilumab BIOLOGICAL

Given IV

Also known as: PF 05082566, PF 5082566, PF-05082566, PF-2566

Arm A (utomilumab, avelumab); Arm C (PF-04518600, utomilumab, avelumab); Arm D (avelumab, utomilumab, radiation therapy); Arm F (avelumab, PF-04518600, radiation therapy)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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 Arm B, subjects may not have had prior OX40 treatment. For Arm C, 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Lermi NO, Gouda MA, Ahmed J, Jiang X, Lee Y, Mohanty V, Derbala M, Stephen B, Jhingran A, Mohammad MM, Joo D, Francisco-Cruz A, Chen H, Calderon LA, Laberiano C, Arrechedera C, Pandurengan R, Gurses S, Yang Y, Solis Soto LM, Ahnert JR, Chen K, Meric-Bernstam F, Koay EJ, Javle M, Haymaker C, Naing A. Tumor microenvironment changes after treatment with avelumab and immune-stimulating agent combinations in patients with advanced solid tumors. Res Sq [Preprint]. 2026 Jan 19:rs.3.rs-7775526. doi: 10.21203/rs.3.rs-7775526/v1.

  PMID: 41646361 DERIVED

• Ahmed J, Knisely A, Torrado C, Stephen B, Yang Y, Song J, Alshawa A, Zarifa A, Jhingran A, Koay EJ, Morris VK, Javle M, Wolff RA, Meric-Bernstam F, Pant S, Rodon J, Naing A. A phase I/II trial of avelumab combinations with ivuxolimab, utomilumab, and radiation therapy in patients with advanced gastrointestinal malignancies. Oncologist. 2025 Mar 10;30(3):oyaf032. doi: 10.1093/oncolo/oyaf032.

  PMID: 40139261 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Prostatic Neoplasms

Interventions

avelumab; Radiotherapy; Radiation; utomilumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Aung Naing
• Organization: M D Anderson Cancer Center

anaing@mdanderson.org

713-563-1930

Study Officials

• Aung Naing

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2017
• First Posted: July 14, 2017
• Study Start: August 2, 2017
• Primary Completion: September 2, 2025
• Study Completion: April 30, 2026
• Last Updated: May 5, 2026
• Results First Posted: October 14, 2025

Record last verified: 2026-04

Locations

US (1)