Vactosertib With Durvalumab in Urothelial Carcinoma Failing Checkpoint Inhibition

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Urothelial Carcinoma Recurrent; Advanced Urothelial Carcinoma
• Intervention / Treatment: Drug: Vactosertib(TEW-7197)/ Durvalumab

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 Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sunjin Hwang, MD; Phone Number: +82 2 6938 0206; Email: sunjin.hwang@medpacto.com

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California San Francisco
      • Contact: Larry Fong, Dr
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
      • Contact: Gurkamal Chatta, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vactosertib+Durvalumab; Vactosertib will be administered in combination with standard dose of durvalumab every four weeks.	Drug: Vactosertib(TEW-7197)/ Durvalumab; Vactosertib (PO) in combination with Durvalumab (IV) every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	ORR by RECIST version 1.1	12months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Tumor Response	TTR by RECIST version 1.1 and iRECIST	Overall study period up to 3years
Best Response	Best response (percent of tumor shrinkage) by RECIST version 1.1 and iRECIST	Overall study period up to 3years
Duration of Response	DoR by RECIST version 1.1 and iRECIST	Overall study period up to 3years
Progression Free Survival	PFS by RECIST version 1.1 and iRECIST	6-month/ 12-month
Overall survival	OS by RECIST version 1.1 and iRECIST	12month
Tumor-specific immune responses	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	Overall study period up to 3years
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

Collaborators and Investigators

• Sponsor: MedPacto, Inc.
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Anticipated): October 15, 2021
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: August 15, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Actual): September 24, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: MP-VAC-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No