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

NCT04235777 | Recruiting Phase 1 FDA Drug FDA Device

• 2 other identifiers: 20001220-C-0012
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bladder Cancer; Urothelial Cancer; Genitourinary Cancer; Urogenital Neoplasms; Urogenital Cancer

Keywords

Immunocytokine; Renal Cell Carcinoma; Urothelial carcinoma; Immune Therapy

Outcome Measures

Primary Outcomes (1)

• safety and tolerability of PDS01ADC and M7824 alone or in combination with SBRT

  The fraction of participants with toxicity noted at each dose level will be reported by grade and type of toxicity identified. Maximum tolerated dose will also be reported.

  until confirmed progression, unacceptable toxicity or trial withdrawal

Secondary Outcomes (3)

• Progression free survival (PFS)

  From start of treatment to time of progression or death, whichever occurs first

• Overall Survival (OS)

  Time from treatment to the date of death from any cause

• Objective response rate (ORR)

  From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented

Study Arms (3)

Arm 1

EXPERIMENTAL

Treatment with M7824 and de-escalating doses of PDS01ADC if appropriate

Drug: PDS01ADC; Drug: M7824

Arm 2

EXPERIMENTAL

Treatment with M7824 and de-escalating doses of PDS01ADC (if appropriate) with sequential SBRT

Radiation: Stereotactic body radiation therapy (SBRT); Drug: PDS01ADC; Drug: M7824

Arm 3

EXPERIMENTAL

Treatment with M7824 and de-escalating doses of PDS01ADC (if appropriate) with concurrent SBRT

Radiation: Stereotactic body radiation therapy (SBRT); Drug: PDS01ADC; Drug: M7824

Interventions

PDS01ADC DRUG

An initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT

Arm 1; Arm 2; Arm 3

M7824 DRUG

1200 mg administered IV every two weeks while on PDS01ADC and with or without SBRT

Arm 1; Arm 2; Arm 3

Stereotactic body radiation therapy (SBRT) RADIATION

A fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and PDS01ADC

Arm 2; Arm 3

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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, Prostate-Specific Antigen (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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Urogenital Neoplasms; Carcinoma, Renal Cell; Carcinoma, Transitional Cell

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Kidney Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Andrea B Apolo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2020
• First Posted: January 22, 2020
• Study Start: July 13, 2020
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-03-19

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)