RECRUITING

Bintrafusp Alfa (M7824) and PDS01ADC Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies

Conditions

Urothelial Cancer Bladder Cancer Genitourinary Cancer Urogenital Neoplasms Urogenital Cancer Immunocytokine Renal Cell Carcinoma Urothelial carcinoma Immune Therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug PDS01ADC triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation. Objective: To learn if M7824 and PDS01ADC, with or without SBRT, can help the immune system to fight cancer better. Eligibility: People 18 and older with cancer that started in the bladder, kidneys, or other genitourinary organs (but not the prostate) and has spread to other parts of the body. Design: Participants will be screened with: medical history physical exam ability to do their normal activities blood tests urine tests electrocardiogram body scans. Participants will give a tumor sample or have a tumor biopsy. Screening tests will be repeated during the study. Participants will get PDS01ADC . It is injected under the skin every 4 weeks. They will also get M7824 through an intravenous (IV) infusion every 2 weeks. For this, a small plastic tube is put into a vein in the arm. They will get these drugs in 28-day cycles until they leave the study. They may have SBRT. Participants will give tissue and saliva samples. Participants will have a follow-up visit 30 days after treatment ends. Then they will get phone calls or emails every 12 weeks indefinitely.

Official Title

A Phase I Study of Bintrafusp Alfa (M7824) and PDS01ADC Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies

Quick Facts

Study Start:2020-07-13

Study Completion:2027-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04235777

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Participants must have histologically or cytologically confirmed diagnosis of a metastatic non-prostate genitourinary tumor. * Participants must have metastatic disease defined as new or progressive lesions on cross-sectional imaging. Radiological evaluation should occur within 21 days prior to enrollment. * Participants must have evaluable or measurable disease, per RECIST 1.1. * Participants in Arms 2 and 3 must have at least one site of disease that is amenable to irradiation (irradiation of up to 4 different sites is permitted) * Participants must have at least one measurable site of disease (according to RECIST criteria) that will not be irradiated. * Participants may have been previously treated with cytotoxic chemotherapy regimen or targeted agent. Participants may have received any number of prior cytotoxic agents. * Participants may have been previously treated with radiation therapy. However, re-irradiation of a previously irradiated site is not permitted unless explicitly discussed with protocol PI and treating radiation oncologist. * Participants may have had prior immunomodulating therapy including therapy with a checkpoint inhibitor but excluding prior treatment with M7824 and/or PDS01ADC. * Participants with locally advanced/metastatic clear cell renal cell cancer must have previously received, refused or been ineligible for either axitinib plus pembrolizumab, cabozantinib plus nivolumab, levantinib plus pembrolizumab, axitinib plus avelumab, nivolumab plus ipilumumab, cabozantinib, pazopanib, sunitinib or axitinib. * Participants with locally advanced or mestastatic germ cell tumors must have received, refused or been ineligible for prior bleomycin plus etoposide plus cisplatin, etoposide plus cisplatin, etoposide plus ifosfamide plus cisplatin, vinblastine plus ifosfamide plus cisplatin, paclitaxel plus ifosfamide plus cisplatin or autologous hematopoietic cell transplantation. * Participants with locally advanced/metastatic urothelial cancer must have previously received, refused or been ineligible for platinum chemotherapy and/or single agent PD-1/PD-L1 inhibitor. * Pre-treatment tissue availability for PD-L1 expression testing is mandatory for enrollment. If tissue is determined to be of insufficient/unsuitable quality/quantity, a pre-treatment biopsy prior to initiation of study therapy will be required. * Male and female participants who are at least 18 years of age on the day of signing the informed consent will be enrolled in the study. * ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%) * Participants must have adequate organ and marrow function as defined below: * leukocytes greater than or equal to 2500mcL * absolute neutrophil count greater than or equal to 1500/mcL * platelets greater than or equal to 100,000/mcL * AST(SGOT)/ALT(SGPT) less than or equal to 1.5 X institutional upper limit of normal * Hgb greater than or equal to 9g/dL (pRBC transfusions are allowed to achieve acceptable Hgb) * Participants may have mild to moderate hepatic impairment with total bilirubin less than or equal to 3.0 x ULN. * For Participants with liver involvement in their tumor, we allow the following: AST less than or equal to 5.0 x ULN, ALT less than or equal to 5.0 x ULN, and bilirubin less than or equal to 3.0 x ULN. * Calculated Creatinine clearance greater than or equal to 20 mL/min (using either CKD-EPY equation) * The effects of M7824 and/or PDS01ADC on the developing human fetus are unknown. For this reason, individuals of child-bearing potential (IOCBP) and individuals able to father a child must agree to use strict and effective contraception during treatment and after the last dose of M7824 administration - at least 65 days after for IOCBP and 125 days after for individuals able to father a child. Should IOCBPs become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately. * HIV-positive participants are eligible if on stable dose of highly active antiretroviral therapy (HAART), CD4 counts are greater than 350 cells/mm3 and viral load is undetectable. * Participants with previously treated brain or CNS metastases are eligible provided that the participant has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to M7824 administration, or any stereotactic radiosurgery was completed at least 2 weeks prior to M7824 administration. * HBV positive participants are eligible-they must have been treated and on a stable dose of antivirals \[eg, entecavir, tenofovir, or lamivudine; (adefovir or interferon are not allowed)\] at study entry and with planned monitoring and management according to appropriate labeling guidance. * HCV positive participants are eligible if participants are on active HCV therapy at study entry and must be on a stable dose without documented clinically significant impaired liver function test or hematologic abnormalities and with planned monitoring and management according to appropriate labeling guidance. * Ability to understand and the willingness to sign a written informed consent document.	* History of allergic reactions attributed to compounds of similar chemical or biologic composition to M7824 and/or PDS01ADC investigational agents used in the study. * Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Participants with a history of bleeding diathesis or recent clinically significant bleeding events considered by the Investigator as high risk for investigational drug treatment are also excluded with the exception of hematuria. * Participants unwilling to accept blood products as medically indicated * Pregnant individuals are excluded from this study because M7824 and/or PDS01ADC are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M7824 and/or PDS01ADC, nursing should be discontinued if the nursing individual is treated with these agents. * Participants with any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required treatment with either systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants with inflammatory bowel disease that have been in remission for at least 5 years whether or not they are currently on immunosuppressive therapy provided that they are not on systemic corticosteroids (\> 10mg daily prednisone equivalent) are eligible. * Participants with any active or recent history of inflammatory bowel disease, active lupus or scleroderma or other medical conditions (i.e., pneumonits with planned SBRT to lung lesion) or genetic radiosensitivity syndromes will be excluded from the study unless deemed eligible by Principal Investigator because these diseases make the participant unsafe or ineligible for radiation therapy with SBRT. * Participants with a currently active second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ or incidental organ-confined prostate cancer found on cystoprostatectomy (provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score \<= 3+4, PSA undetectable). Participants are not considered to have a currently active malignancy if they have completed therapy and are free of disease for \>= 2 years and currently do not require systemic therapy. * Participants having tumor lesion(s) in the liver or chest which are 10 cm or larger.

Inclusion Criteria

Exclusion Criteria

* Participants must have histologically or cytologically confirmed diagnosis of a metastatic non-prostate genitourinary tumor.
* Participants must have metastatic disease defined as new or progressive lesions on cross-sectional imaging. Radiological evaluation should occur within 21 days prior to enrollment.
* Participants must have evaluable or measurable disease, per RECIST 1.1.
* Participants in Arms 2 and 3 must have at least one site of disease that is amenable to irradiation (irradiation of up to 4 different sites is permitted)
* Participants must have at least one measurable site of disease (according to RECIST criteria) that will not be irradiated.
* Participants may have been previously treated with cytotoxic chemotherapy regimen or targeted agent. Participants may have received any number of prior cytotoxic agents.
* Participants may have been previously treated with radiation therapy. However, re-irradiation of a previously irradiated site is not permitted unless explicitly discussed with protocol PI and treating radiation oncologist.
* Participants may have had prior immunomodulating therapy including therapy with a checkpoint inhibitor but excluding prior treatment with M7824 and/or PDS01ADC.
* Participants with locally advanced/metastatic clear cell renal cell cancer must have previously received, refused or been ineligible for either axitinib plus pembrolizumab, cabozantinib plus nivolumab, levantinib plus pembrolizumab, axitinib plus avelumab, nivolumab plus ipilumumab, cabozantinib, pazopanib, sunitinib or axitinib.
* Participants with locally advanced or mestastatic germ cell tumors must have received, refused or been ineligible for prior bleomycin plus etoposide plus cisplatin, etoposide plus cisplatin, etoposide plus ifosfamide plus cisplatin, vinblastine plus ifosfamide plus cisplatin, paclitaxel plus ifosfamide plus cisplatin or autologous hematopoietic cell transplantation.
* Participants with locally advanced/metastatic urothelial cancer must have previously received, refused or been ineligible for platinum chemotherapy and/or single agent PD-1/PD-L1 inhibitor.
* Pre-treatment tissue availability for PD-L1 expression testing is mandatory for enrollment. If tissue is determined to be of insufficient/unsuitable quality/quantity, a pre-treatment biopsy prior to initiation of study therapy will be required.
* Male and female participants who are at least 18 years of age on the day of signing the informed consent will be enrolled in the study.
* ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%)
* Participants must have adequate organ and marrow function as defined below:
* leukocytes greater than or equal to 2500mcL
* absolute neutrophil count greater than or equal to 1500/mcL
* platelets greater than or equal to 100,000/mcL
* AST(SGOT)/ALT(SGPT) less than or equal to 1.5 X institutional upper limit of normal
* Hgb greater than or equal to 9g/dL (pRBC transfusions are allowed to achieve acceptable Hgb)
* Participants may have mild to moderate hepatic impairment with total bilirubin less than or equal to 3.0 x ULN.
* For Participants with liver involvement in their tumor, we allow the following: AST less than or equal to 5.0 x ULN, ALT less than or equal to 5.0 x ULN, and bilirubin less than or equal to 3.0 x ULN.
* Calculated Creatinine clearance greater than or equal to 20 mL/min (using either CKD-EPY equation)
* The effects of M7824 and/or PDS01ADC on the developing human fetus are unknown. For this reason, individuals of child-bearing potential (IOCBP) and individuals able to father a child must agree to use strict and effective contraception during treatment and after the last dose of M7824 administration - at least 65 days after for IOCBP and 125 days after for individuals able to father a child. Should IOCBPs become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately.
* HIV-positive participants are eligible if on stable dose of highly active antiretroviral therapy (HAART), CD4 counts are greater than 350 cells/mm3 and viral load is undetectable.
* Participants with previously treated brain or CNS metastases are eligible provided that the participant has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to M7824 administration, or any stereotactic radiosurgery was completed at least 2 weeks prior to M7824 administration.
* HBV positive participants are eligible-they must have been treated and on a stable dose of antivirals \[eg, entecavir, tenofovir, or lamivudine; (adefovir or interferon are not allowed)\] at study entry and with planned monitoring and management according to appropriate labeling guidance.
* HCV positive participants are eligible if participants are on active HCV therapy at study entry and must be on a stable dose without documented clinically significant impaired liver function test or hematologic abnormalities and with planned monitoring and management according to appropriate labeling guidance.
* Ability to understand and the willingness to sign a written informed consent document.

* History of allergic reactions attributed to compounds of similar chemical or biologic composition to M7824 and/or PDS01ADC investigational agents used in the study.
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Participants with a history of bleeding diathesis or recent clinically significant bleeding events considered by the Investigator as high risk for investigational drug treatment are also excluded with the exception of hematuria.
* Participants unwilling to accept blood products as medically indicated
* Pregnant individuals are excluded from this study because M7824 and/or PDS01ADC are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M7824 and/or PDS01ADC, nursing should be discontinued if the nursing individual is treated with these agents.
* Participants with any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required treatment with either systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Participants with inflammatory bowel disease that have been in remission for at least 5 years whether or not they are currently on immunosuppressive therapy provided that they are not on systemic corticosteroids (\> 10mg daily prednisone equivalent) are eligible.
* Participants with any active or recent history of inflammatory bowel disease, active lupus or scleroderma or other medical conditions (i.e., pneumonits with planned SBRT to lung lesion) or genetic radiosensitivity syndromes will be excluded from the study unless deemed eligible by Principal Investigator because these diseases make the participant unsafe or ineligible for radiation therapy with SBRT.
* Participants with a currently active second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ or incidental organ-confined prostate cancer found on cystoprostatectomy (provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score \<= 3+4, PSA undetectable). Participants are not considered to have a currently active malignancy if they have completed therapy and are free of disease for \>= 2 years and currently do not require systemic therapy.
* Participants having tumor lesion(s) in the liver or chest which are 10 cm or larger.

Contacts and Locations

Study Contact

Lisa Ley, R.N.

CONTACT

(240) 858-3524

lisa.ley@nih.gov

Andrea B Apolo, M.D.

CONTACT

(301) 480-0536

apoloab@mail.nih.gov

Principal Investigator

Andrea B Apolo, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Andrea B Apolo, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-07-13

Study Completion Date2027-12-01

Study Record Updates

Study Start Date2020-07-13

Study Completion Date2027-12-01

Terms related to this study

Keywords Provided by Researchers

Immunocytokine
Renal Cell Carcinoma
Urothelial carcinoma
Immune Therapy

Additional Relevant MeSH Terms

Urothelial Cancer
Bladder Cancer
Genitourinary Cancer
Urogenital Neoplasms
Urogenital Cancer