Urothelial CancerPhase 1NCT04235777
Bintrafusp Alfa (M7824) and PDS01ADC Alone and in Combination With Stereotactic Body Radiation Therapy (SBRT) in Adults With Metastatic Non-Prostate Genitourinary Malignancies
A Phase 1 study testing Stereotactic body radiation therapy (SBRT), PDS01ADC and M7824 in people with Urothelial Cancer and Bladder Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Urothelial Cancer, Bladder Cancer, Genitourinary Cancer
- What is being tested?
- Stereotactic body radiation therapy (SBRT), PDS01ADC and M7824
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jul 2020to 1 Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 29Show fewer
- 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
- Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) less than or equal to 1.5 X institutional upper limit of normal (ULN)
- Hemoglobin (Hgb) greater than or equal to 9g/dL (Packed red blood cells (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.
- Human Immunoodeficiency Virus (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 central nervous system (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.
- Hepatitis B Virus (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.
- Hepatitis B Virus (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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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
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.
Read more
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.
Read the detailed description
Background:
- Urothelial carcinoma (UC), renal cell carcinoma (RCC) and other non-prostate genitourinary cancers are lethal in the metastatic state.
- Immune checkpoint inhibitors targeting the Programmed Cell Death Protein 1 (PD-1)/ Programmed Death-Ligand 1 (PD-L1) pathway have greatly changed clinical management of metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC).
- Several PD-1/PD-L1 inhibitors are Food and Drug Administration (FDA)-approved for non-prostate genitourinary cancers including five agents for second-line mUC, two agents for first-line cisplatin-ineligible mUC and one approval for second-line mRCC. However, response rates are modest (approximately 15-21% in mUC and 25% in mRCC).
- Therefore, novel combination strategies are needed to extend benefit of immunotherapy to the remaining approximate 75% of non-responders.
- Bintrafusp alfa (M7824) is a novel first-in-class bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused to the extracellular domain of human Transforming Growth Factor Beta (TGF-beta) receptor II (TGF beta RII), which effectively functions to sequester or trap all three TGF- beta isoforms. A phase I study of M7824 (NCT02517398) demonstrated a manageable safety profile and clinical efficacy among patients with heavily pre-treated advanced solid tumors.
- PDS01ADC is an immunocytokine composed of two interleukin (IL)-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA) allowing for targeted delivery of pro-inflammatory cytokine, IL-12, to necrotic portions of tumor at sites of DNA exposure to promote local immunomodulation. PDS01ADC has demonstrated promising pre-clinical activity (including durable responses) as well as an encouraging safety and anti-tumor activity in an ongoing Phase Ib clinical trial in combination with an anti-PD-L1 agent (NCT02994953).
- Currently, no clinical data exists for the combination of M7824 plus PDS01ADC. Preclinical data suggest synergy between these agents and the available clinical data suggest that the combination of M7824 plus PDS01ADC is likely to be well-tolerated.
- There is a growing body of evidence suggesting that stereotactic body radiation therapy (SBRT), which delivers highly conformal high-dose radiation, can promote anti-tumor immune responses both locally and systemically as well as synergize with immune checkpoint inhibitors and other forms of immunotherapy.
- SBRT-induced dsDNA breaks are tumoricidal and may promote immunogenicity. SBRT also upregulates PD-L1 expression and leads to activation of TGF-beta. SBRT may enhance intratumoral binding of DNA-damage localizing agent, PDS01ADC. Preclinical models have demonstrated impressive synergy with radiation plus M7824 and radiation plus PDS01ADC.
- We hypothesize that an immune-intensification approach involving M7824 plus PDS01ADC combined with SBRT will enhance therapeutic efficacy and clinical benefit in patients with metastatic non-prostate genitourinary cancers with an acceptable safety profile.
- The combination of M7824 with PDS01ADC with or without administration of SBRT (sequential or concurrent) will aid evaluation of safety signals contributed by each agent and will provide insight into a currently unanswered question regarding the optimal timing and sequencing of SBRT and immunotherapy.
Objectives:
-Determine the safety and tolerated doses of PDS01ADC and M7824 alone or in combination with SBRT (Stereotactic Body Radiation Therapy) administered sequentially or concurrently in participants with metastatic non-prostate genitourinary cancers
Eligibility:
- Participants must have a histologically confirmed diagnosis of metastatic non-prostate genitourinary cancer.
- Participants must have metastatic disease defined as new or progressive lesions on cross-sectional imaging.
- Participants must have at least:
- One site of disease that is amenable to irradiation (a maximum of four sites may be irradiated) (in Arm 2 and 3 only)
- One measurable site of disease (according to Response Evaluation Criteria) that will not be irradiated.
- 18 years of age or older
Design:
- This is an open label, non-randomized, three-stage phase I trial of M7824 and PDS01AD or M7824 and PDS01ADC in combination with either sequential or concurrent SBRT.
- M7824 (intravenous 1200 mg) and SBRT (8 Gy x 3 fractions) are planned with de-escalating dose schedule for PDS01ADC. Dose de-escalation of PDS01ADC will be done if toxicities start at dose 16.8 mcg/kg.
- Up to 66 evaluable participants will be seen.
- Participants will receive treatment in cycles consisting of 4 weeks.
- Conditions
- Urothelial Cancer, Bladder Cancer, Genitourinary Cancer, Urogenital Neoplasms, Urogenital Cancer
- Being tested
- Stereotactic body radiation therapy (SBRT), PDS01ADC, M7824
- Keywords
- Immunocytokine, Renal Cell Carcinoma, Urothelial carcinoma, Immune Therapy
- Medical subject headings
- Urinary Bladder Neoplasms, Urogenital Neoplasms, Carcinoma, Renal Cell, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic body radiation therapy (SBRT)Radiation
A fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and PDS01ADC
PDS01ADCDrug
An initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT
M7824Drug
1200 mg administered IV every two weeks while on PDS01ADC and with or without SBRT
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Treatment with M7824 and de-escalating doses of PDS01ADC if appropriate Receives: Drug: PDS01ADC; Drug: M7824 |
| Arm 2 | Experimental | Treatment with M7824 and de-escalating doses of PDS01ADC (if appropriate) with sequential SBRT Receives: 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 Receives: Radiation: Stereotactic body radiation therapy (SBRT); Drug: PDS01ADC; Drug: M7824 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: until confirmed progression, unacceptable toxicity or trial withdrawal
Secondary outcomes (3)
Progression free survival (PFS)
duration of time from start of treatment to time of progression or death, whichever occurs first
Measured: From start of treatment to time of progression or death, whichever occurs first
Overall Survival (OS)
Time from the start of treatment that participants are still alive.
Measured: Time from treatment to the date of death from any cause
Objective response rate (ORR)
the fraction of evaluable participants with a PR or CR at the end of treatment with M7824 will be reported along with 80% and 95% two-sided confidence intervals for each arm
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2020
- Study start13 Jul 2020
- Primary completion31 Aug 2026
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andrea B Apolo, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04235777
- Sponsor's protocol ID
- 200012
- Other IDs
- 20-C-0012
- Status last verified
- 23 Sep 2026
- First submitted
- 18 Jan 2020
- Last updated
- 28 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04235777
- Acronym / sponsor ID
- 200012
- Conditions
- Urothelial Cancer, Bladder Cancer, Genitourinary Cancer, Urogenital Neoplasms, Urogenital Cancer
- Keywords
- Immunocytokine, Renal Cell Carcinoma, Urothelial carcinoma, Immune Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 22 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 13 Jul 2020 (actual)
- Primary completion
- 31 Aug 2026 (actual)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 22 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
- Urothelial carcinoma (UC), renal cell carcinoma (RCC) and other non-prostate genitourinary cancers are lethal in the metastatic state.
- Immune checkpoint inhibitors targeting the Programmed Cell Death Protein 1 (PD-1)/ Programmed Death-Ligand 1 (PD-L1) pathway have greatly changed clinical management of metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma (mRCC).
- Several PD-1/PD-L1 inhibitors are Food and Drug Administration (FDA)-approved for non-prostate genitourinary cancers including five agents for second-line mUC, two agents for first-line cisplatin-ineligible mUC and one approval for second-line mRCC. However, response rates are modest (approximately 15-21% in mUC and 25% in mRCC).
- Therefore, novel combination strategies are needed to extend benefit of immunotherapy to the remaining approximate 75% of non-responders.
- Bintrafusp alfa (M7824) is a novel first-in-class bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused to the extracellular domain of human Transforming Growth Factor Beta (TGF-beta) receptor II (TGF beta RII), which effectively functions to sequester or trap all three TGF- beta isoforms. A phase I study of M7824 (NCT02517398) demonstrated a manageable safety profile and clinical efficacy among patients with heavily pre-treated advanced solid tumors.
- PDS01ADC is an immunocytokine composed of two interleukin (IL)-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA) allowing for targeted delivery of pro-inflammatory cytokine, IL-12, to necrotic portions of tumor at sites of DNA exposure to promote local immunomodulation. PDS01ADC has demonstrated promising pre-clinical activity (including durable responses) as well as an encouraging safety and anti-tumor activity in an ongoing Phase Ib clinical trial in combination with an anti-PD-L1 agent (NCT02994953).
- Currently, no clinical data exists for the combination of M7824 plus PDS01ADC. Preclinical data suggest synergy between these agents and the available clinical data suggest that the combination of M7824 plus PDS01ADC is likely to be well-tolerated.
- There is a growing body of evidence suggesting that stereotactic body radiation therapy (SBRT), which delivers highly conformal high-dose radiation, can promote anti-tumor immune responses both locally and systemically as well as synergize with immune checkpoint inhibitors and other forms of immunotherapy.
- SBRT-induced dsDNA breaks are tumoricidal and may promote immunogenicity. SBRT also upregulates PD-L1 expression and leads to activation of TGF-beta. SBRT may enhance intratumoral binding of DNA-damage localizing agent, PDS01ADC. Preclinical models have demonstrated impressive synergy with radiation plus M7824 and radiation plus PDS01ADC.
- We hypothesize that an immune-intensification approach involving M7824 plus PDS01ADC combined with SBRT will enhance therapeutic efficacy and clinical benefit in patients with metastatic non-prostate genitourinary cancers with an acceptable safety profile.
- The combination of M7824 with PDS01ADC with or without administration of SBRT (sequential or concurrent) will aid evaluation of safety signals contributed by each agent and will provide insight into a currently unanswered question regarding the optimal timing and sequencing of SBRT and immunotherapy.
Objectives:
-Determine the safety and tolerated doses of PDS01ADC and M7824 alone or in combination with SBRT (Stereotactic Body Radiation Therapy) administered sequentially or concurrently in participants with metastatic non-prostate genitourinary cancers
Eligibility:
- Participants must have a histologically confirmed diagnosis of metastatic non-prostate genitourinary cancer.
- Participants must have metastatic disease defined as new or progressive lesions on cross-sectional imaging.
- Participants must have at least:
- One site of disease that is amenable to irradiation (a maximum of four sites may be irradiated) (in Arm 2 and 3 only)
- One measurable site of disease (according to Response Evaluation Criteria) that will not be irradiated.
- 18 years of age or older
Design:
- This is an open label, non-randomized, three-stage phase I trial of M7824 and PDS01AD or M7824 and PDS01ADC in combination with either sequential or concurrent SBRT.
- M7824 (intravenous 1200 mg) and SBRT (8 Gy x 3 fractions) are planned with de-escalating dose schedule for PDS01ADC. Dose de-escalation of PDS01ADC will be done if toxicities start at dose 16.8 mcg/kg.
- Up to 66 evaluable participants will be seen.
- Participants will receive treatment in cycles consisting of 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: PDS01ADC, Drug: M7824Treatment with M7824 and de-escalating doses of PDS01ADC if appropriate |
| Arm 2 | Experimental | Radiation: Stereotactic body radiation therapy (SBRT), Drug: PDS01ADC, Drug: M7824Treatment with M7824 and de-escalating doses of PDS01ADC (if appropriate) with sequential SBRT |
| Arm 3 | Experimental | Radiation: Stereotactic body radiation therapy (SBRT), Drug: PDS01ADC, Drug: M7824Treatment with M7824 and de-escalating doses of PDS01ADC (if appropriate) with concurrent SBRT |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic body radiation therapy (SBRT)A fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and PDS01ADC | Radiation | Arm 2, Arm 3 |
| PDS01ADCAn initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT | Drug | Arm 1, Arm 2, Arm 3 |
| M78241200 mg administered IV every two weeks while on PDS01ADC and with or without SBRT | Drug | Arm 1, Arm 2, Arm 3 |
Primary outcome
safety and tolerability of PDS01ADC and M7824 alone or in combination with SBRT
Time frame: until confirmed progression, unacceptable toxicity or trial withdrawal
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.
3 secondary outcomes
Progression free survival (PFS)
Time frame: From start of treatment to time of progression or death, whichever occurs first
Overall Survival (OS)
Time frame: Time from treatment to the date of death from any cause
Objective response rate (ORR)
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request.@@@@@@@@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Related trials for Urothelial Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
Registry Platform Urologic Cancer
Renal Cell Carcinoma, Urothelial Carcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea B Apolo, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Stereotactic body radiation therapy (SBRT), PDS01ADC and M7824 in people with Urothelial Cancer and Bladder Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety and tolerability of PDS01ADC and M7824 alone or in combination with SBRT (time frame: until confirmed progression, unacceptable toxicity or trial withdrawal). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2026.