Vactosertib With Durvalumab in Urothelial Carcinoma Failing Checkpoint Inhibition

Advanced Urothelial Carcinoma Clinical Trial

Official title:

A Phase 2 Study of TGF-β Inhibition (Vactosertib) With Anti-PD-L1 (Durvalumab) in Patients With Advanced or Recurrent Urothelial Carcinoma Failing to Achieve Response With Checkpoint Inhibition

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04064190
• Other study ID #: MP-VAC-202
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 15, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: September 2021
• Source: MedPacto, Inc.
• Contact: Sunjin Hwang, MD
• Phone: +82 2 6938 0206
• Email: sunjin.hwang[@]medpacto.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Urothelial Carcinoma
• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma Recurrent

Intervention

Drug:
• Vactosertib(TEW-7197)/ Durvalumab
Vactosertib (PO) in combination with Durvalumab (IV) every 4 weeks

Locations

Country	Name	City	State
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
MedPacto, Inc.	AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

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