Vactosertib with Durvalumab in Urothelial Carcinoma Failing Checkpoint Inhibition

Phase 2

Withdrawn

• Conditions: Urothelial Carcinoma Recurrent; Advanced Urothelial Carcinoma
• Interventions: Drug: Vactosertib(TEW-7197)/ Durvalumab

• Registration Number: NCT04064190
• Lead Sponsor: MedPacto, Inc.

Brief Summary

This is Phase 2, open label, non randomized single arm study to determine whether the administration of vactosertib with durvalumab will provide meaningful increases in the Overall Response Rate (ORR) in patients with urothelial cancers that fail to achieve a response with anti-PD-1/PD-L1 based regimens

Detailed Description

This is a Phase 2, open-label, non-randomized, two-cohort multi center study with a safety run-in of 6 patients in Cohort 1. It is anticipated that a total of 48 patients will be enrolled.

Durvalumab will be administered with the standard regimen of 1500 mg intravenously (IV) every four weeks. Vactosertib will be administered at a dose of 300 mg PO BID for 5 days per week All treatment will be administered up to two years and the trial is anticipated to be completed over a period of 36 months.

Study Timeline

• Study First Submitted: 2019-08-15
• Study First Submitted QC: 2019-08-19
• Study First Posted: 2019-08-21
• Study Start: 2019-12-13
• Primary Completion: 2023-12-30
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-04
• Last Update Posted: 2024-12-09
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrollment
2. Histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra.
3. Prior anti-PD-(L)1 treatment.
4. Measurable disease per RECIST 1.1 assessed by computed tomography (CT) scan or MRI.
5. Recurrent disease after any prior platinum-based chemotherapy regimen or ineligible for platinum therapy.
6. Adequate organ and marrow function as defined
7. Must have a life expectancy of at least 12 weeks.
8. Body weight > 30 kg

Exclusion Criteria

1. History of allogeneic organ transplantation.
2. Active or prior documented autoimmune or inflammatory disorders
3. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure .
4. History of another primary malignancy
5. History of leptomeningeal carcinomatosis.
6. History of active primary immunodeficiency.
7. Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus .
8. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vactosertib+Durvalumab	Vactosertib(TEW-7197)/ Durvalumab	Vactosertib will be administered in combination with standard dose of durvalumab every four weeks.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	12months	ORR by RECIST version 1.1

Secondary Outcome Measures

Name	Time	Method
Time to Tumor Response	Overall study period up to 3years	TTR by RECIST version 1.1 and iRECIST
Best Response	Overall study period up to 3years	Best response (percent of tumor shrinkage) by RECIST version 1.1 and iRECIST
Duration of Response	Overall study period up to 3years	DoR by RECIST version 1.1 and iRECIST
Progression Free Survival	6-month/ 12-month	PFS by RECIST version 1.1 and iRECIST
Overall survival	12month	OS by RECIST version 1.1 and iRECIST
Tumor-specific immune responses	Overall study period up to 3years	tumor-specific immune responses within on-therapy biopsies measured by increased T cell infiltration and increased IFN-λ signature. and the correlation with outcome as measured by ORR, TTR, DoR, PFS and OS
Incidence of Treatment-Emergent Adverse Events [Safety and tolerability]	Overall study period up to 3years	To assess safety and tolerability of vactosertib administered concurrent with Durvalumab in patients with urothelial carcinoma failing checkpoint inhibition

Trial Locations

Locations (2)

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States