Urothelial Carcinoma
Conditions
Keywords
M1774, locally advanced and unresectable or metastatic urothelial carcinoma, bladder cancer
Brief summary
The purpose of this study is to assess the antitumor activity of avelumab in combination with tuvusertib in terms of objective response in participants with advanced urothelial carcinoma. Study details include: Condition/Disease: Participants with urothelial carcinoma (locally advanced and unresectable, or metastatic) that has progressed on prior anti-PD-(L)1 therapy Treatment Duration: Participants will be treated until progressive disease, death, or discontinuation due to e.g. withdrawal of consent or lost to follow-up Visit Frequency: While receiving study intervention, participants will visit the site twice per every 21-day study intervention period. 1 week after end of study intervention, participants will visit the site for an End of Study Intervention Visit, followed by 2 Safety Follow-Up visits at 1 and 3 months after last dose, and thereafter have remote Long-Term Follow-up every 3 months. Study Duration: The overall study is planned to close after the last participant has been followed up for at least 12 months.
Interventions
DRUGAvelumab
Participants will be administered Avelumab intravenously (IV).
DRUGTuvusertib
Participants will be administered Tuvusertib orally.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed, locally advanced, and unresectable or metastatic urothelial carcinoma. * No more than 2 lines of therapy for advanced disease. Chemotherapy followed by avelumab (switch maintenance) counts as 1 line of therapy. Additionally, (neo)-adjuvant chemotherapy for Muscle invasive bladder cancer with recurrence or progression within 12 months of last dose, counts as a line of therapy. * Measurable disease by RECIST 1.1, as assessed by the Investigator. * Eastern Cooperative Oncology Group Performance status 0 to 1. * Adequate hematologic function as indicated by: * Platelet count more than or equal to 100,000 per microliter * Absolute neutrophil count more than or equal to 1,500 per microliter with no growth factor treatment within the last 14 days * Hemoglobin more than or equal to 9.0 gram/deciliter with no erythropoietin or red blood cell transfusion within the last 14 days * Only one line of an antibody-drug conjugate (ADC) is allowed. * Other protocol defined inclusion criteria could apply.
Exclusion criteria
* Any condition, including any uncontrolled disease state other than aUC, that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation. * Any known additional malignancy that is progressing and/or requires active treatment including adjuvant hormonal therapy. * Presence of brain metastases unless clinically stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention and any neurologic symptoms have returned to baseline and sequelae that are a consequence of the treatment of the brain metastases are acceptable), no evidence of new brain metastases, and on a stable or decreasing dose or without steroids for at least 14 days prior to first dose of study intervention. Participants with carcinomatous meningitis are excluded regardless of clinical stability. * Serious gastrointestinal bleeding within 3 months, refractory nausea and vomiting, uncontrolled diarrhea, known malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes, other chronic gastrointestinal disease (including exocrine pancreatic insufficiency requiring pancreatic enzyme replacement therapy), and/or other situations that may preclude adequate absorption of oral medications. * Other protocol defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Confirmed Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 as Assessed by Investigator in Participants with Selected Tumor Chromatin Modifier Mutations | Up to 18 months |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator | Up to 18 months |
| Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator | Up to 18 months |
| Overall Survival (OS) | From the date of randomization until death, assessed up to 1.5 years |
| Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs | Up to 18 months |
| Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator | Up to 18 months |
| Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator in Subpopulations as Defined by Selected Tumor Biomarkers | Up to 18 months |
| Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator in Subpopulations as Defined by Selected Tumor Biomarkers | Up to 18 months |
| Overall Survival (OS) in Subpopulations as Defined by Selected Tumor Biomarkers | From the date of randomization until death, assessed up to 1.5 years |
| Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator in Subpopulations as Defined by Selected Tumor Biomarkers | Up to 18 months |
Outcome results
None listed