M7824, M9241, and SBRT for Genitourinary Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Andrea B Apolo, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Systemic corticosteroids, Immunosuppressive medications

Disqualifiers: Autoimmune disease, Uncontrolled illness, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain treatments like systemic corticosteroids or immunosuppressive medications, you may need to adjust them. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Bintrafusp Alfa (M7824) for genitourinary cancer?

Research shows that drugs targeting PD-1/PD-L1, like Bintrafusp Alfa, have shown promise in treating urothelial bladder cancer, offering new hope for patients. These types of drugs are becoming a standard treatment option due to their effectiveness in improving survival rates in certain cancers.

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Is the treatment with Bintrafusp Alfa, M9241, and SBRT generally safe for humans?

Bintrafusp Alfa has been studied in various cancer types and has shown a manageable safety profile, meaning that while there may be some side effects, they are generally considered acceptable and can be managed. The recommended doses have been determined to maintain effectiveness while minimizing adverse effects.

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What makes the drug Bintrafusp Alfa unique for treating genitourinary cancer?

Bintrafusp Alfa is unique because it is a first-in-class bifunctional fusion protein that targets both TGF-β (a protein that can help cancer cells grow) and PD-L1 (a protein that helps cancer cells hide from the immune system), potentially offering a new way to treat cancers that are resistant to other therapies.

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Eligibility Criteria

Adults over 18 with genitourinary cancers (excluding prostate cancer) that have spread, who can provide a tumor sample and are not pregnant or breastfeeding. Participants must be able to perform daily activities, have adequate organ function, agree to use contraception, and may have had prior treatments but not with M7824/M9241.

Inclusion Criteria

You have a condition that can be measured or evaluated by the doctors.

I have had radiation therapy before, but not on the same area twice.

I have advanced kidney cancer and cannot take standard treatments.

Exclusion Criteria

I am unwilling to receive blood products even if needed for my treatment.

I have an autoimmune disease or have been treated with high-dose steroids or immunosuppressants.

I have a tumor in my liver or chest that is larger than 10 cm.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive PDS01ADC injections every 4 weeks and M7824 infusions every 2 weeks in 28-day cycles, with optional SBRT

Until progression or unacceptable toxicity

Bi-weekly visits for M7824 infusion

Follow-up

Participants have a follow-up visit 30 days after treatment ends, followed by phone calls or emails every 12 weeks indefinitely

Indefinite

1 in-person visit, then remote follow-ups

Participant Groups

The trial is testing the effectiveness of two drugs, M7824 and M9241 alone or combined with SBRT radiation therapy in treating metastatic non-prostate genitourinary cancers. The goal is to see if these treatments improve the immune system's ability to fight cancer.

Group I: Arm 3 Experimental Treatment 3 Interventions

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

Group II: Arm 2 Experimental Treatment 3 Interventions

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

Group III: Arm 1 Experimental Treatment 2 Interventions

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. Hungary pubmed.ncbi.nlm.nih.gov

[Immunotherapy in the treatment of genitourinary cancers]. [2018] In this clinical review we provide information regarding advance and main achievements in the immunotherapy of genitourinary, particularly renal cell and prostate cancer. Nivolumab treatment became the new standard of care in locally advanced or metastatic renal cell cancer after failure on tyrosine kinase inhibitor treatment. Sipuleucel-T prolonged survival in patients with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer but had no effect on progression-free survival. Based on the results of phase I/II trials anti-PD-1/PD-L1 monoclonal antibodies are a new hope in the treatment of urothelial bladder cancer. Regarding germ cell tumors basic research is ongoing.

2. United States pubmed.ncbi.nlm.nih.gov

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer. [2021] The large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).

3. England pubmed.ncbi.nlm.nih.gov

Sipuleucel-T (APC8015) for prostate cancer. [2022] Sipuleucel-T (Provenge; APC8015; Dendreon Corp, WA, USA) is a novel immunotherapeutic cellular product, which includes autologous dendritic cells pulsed ex vivo with a recombinant fusion protein (PA2024) consisting of granulocyte macrophage colony-stimulating factor and prostatic acid phosphatase. Two Phase II trials in men with androgen-dependent biochemically relapsed prostate cancer have demonstrated a decrease in prostate-specific antigen and prolongation in prostate-specific antigen doubling time. In men with hormone-refractory prostate cancer, clinical trials have demonstrated both biological activity and clinical response to sipuleucel-T. Data from two Phase III trials in men with asymptomatic, metastatic hormone-refractory prostate cancer demonstrated an improved median overall survival in men who received sipuleucel-T compared with placebo. Clinical trials are ongoing or are being developed to evaluate sipuleucel-T in various prostate cancer disease states and in combination with other treatment modalities.

4. Germany pubmed.ncbi.nlm.nih.gov

[The role of immunooncology in the treatment of urothelial cancer]. [2019] Data published in November 2016 showed a significant survival benefit for the PD-1 antibody Pembrolizumab in the second-line treatment of metastatic urothelial cancer in comparison to standard chemotherapy. Other PD-1/PD-L1 antibodies are being tested in advanced clinical trials. This class of substances will become standard of care from the time of their approval which is expected for 2017 and will replace vinflunine, which is currently recommended in the German guideline. PD-1/PD-L1 directed substances are also being tested as a first line treatment of metastatic urothelial carcinoma. Monotherapy is evaluated as well as combination treatments with CTLA-4 inhibitors of conventional chemotherapy. First data are expected at the end of 2017.A new strategy is the application of PD-1/PD-L1 directed substances in the perioperative treatment of patients with a muscle-invasive urothelial carcinoma after complete surgical resection (cystectomy or nephroureterectomy). Two international phase III trials evaluate an adjuvant immunotherapy with nivolumab and atezolizumab. Recruitment will be completed in 2018.

5. England pubmed.ncbi.nlm.nih.gov

Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial. [2023] Locally advanced or metastatic urothelial carcinoma is generally incurable and has scarce treatment options, especially for cisplatin-ineligible patients previously treated with PD-1 or PD-L1 therapy. Enfortumab vedotin is an antibody-drug conjugate directed at Nectin-4, a protein highly expressed in urothelial carcinoma. We aimed to evaluate the efficacy and safety of enfortumab vedotin in the post-immunotherapy setting in cisplatin-ineligible patients.

6. United States pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial. [2023] The safety and efficacy of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor β (TGF-β) receptor II (a TGF-β "trap") fused to a human immunoglobulin G1 antibody blocking programmed death-ligand 1 (PD-L1), was evaluated in patients with advanced NSCLC.

7. United States pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1-High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial. [2023] Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1-high advanced NSCLC.

8. England pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors. [2023] Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor beta receptor II (a TGF-β "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed cell death 1 ligand 1 (PD-L1). We report the efficacy and safety in patients with non-small cell lung cancer (NSCLC) that progressed following anti-PD-(L)1 therapy.

9. United States pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. [2020] Bintrafusp alfa, an innovative first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking programmed death ligand 1, has shown promising antitumor activity and manageable safety.

10. United States pubmed.ncbi.nlm.nih.gov

Selection of the Recommended Phase 2 Dose for Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1. [2021] Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (TGF-β "trap") fused to a human IgG1-blocking PD-L1, showed a manageable safety profile and clinical activity in phase I studies in patients with heavily pretreated advanced solid tumors. The recommended phase 2 dose (RP2D) was selected based on integration of modeling, simulations, and all available data. A 1,200-mg every 2 weeks (q2w) dose was predicted to maintain serum trough concentration (Ctrough ) that inhibits all targets of bintrafusp alfa in circulation in > 95% of patients, and a 2,400-mg every 3 weeks (q3w) dose was predicted to have similar Ctrough . A trend toward an association between exposure and efficacy variables and a relatively stronger inverse association between clearance and efficacy variables were observed. Exposure was either weakly or not correlated with probability of adverse events. The selected intravenous RP2D of bintrafusp alfa is 1,200 mg q2w or 2,400 mg q3w.

11. United States pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFβ and PD-L1, in Asian Patients with Pretreated Recurrent or Refractory Gastric Cancer. [2021] Patients with advanced gastric/gastroesophageal junction cancer (GC/GEJC) have limited treatment options after first-line therapy. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGFβRII receptor (a TGFβ "trap") fused to a human IgG1 antibody against programmed death ligand 1 (PD-L1), potentially offering a new treatment approach for these patients. We report results for bintrafusp alfa in GC/GEJC.