Study BT7480-100 in Patients With Advanced Malignancies Associated With Nectin-4 Expression

Advanced Solid Tumor Clinical Trial

Official title:

Phase 1/2 Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT7480 in Patients With Nectin-4 Associated Advanced Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05163041
• Other study ID #: BT7480-100
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 2, 2021
• Est. completion date: December 2025

Study information

• Verified date: March 2023
• Source: BicycleTx Limited
• Contact: BicycleTx Limited
• Phone: 617-945-8155
• Email: clinicalstudies[@]bicycletx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical study is evaluating a drug called BT7480 alone and in combination with nivolumab in participants with advanced solid tumors associated with Nectin-4 expression. The main goals of the study are to: - Find the recommended dose of BT7480 that can be given safely to participants alone and in combination with nivolumab - Learn about the side effects and effectiveness of BT7480 alone and in combination with nivolumab - Learn about the effect BT7480 has on the body and how BT7480 is cleared by the body - Learn about the side effects and effectiveness of BT7480 in patients with reduced kidney function

Description:

BT7480 is a tumor targeted immune cell agonist consisting of three bicyclic peptides (Bicycle®) conjugated via a linker, one that binds selectively to Nectin-4 and two that bind to CD137. This study is a Phase 1/2, multicenter, first-in-human, open-label study of BT7480 given as a single agent and in combination with nivolumab once weekly. There are five parts to the trial: 1) Phase 1 dose escalation in patients with select advanced solid tumors primarily to evaluate safety and tolerability of BT7480 as a monotherapy and determine a recommended Phase 2 dose (RP2D); 2) Phase 1 dose escalation in combination with nivolumab, once the monotherapy RP2D has been determined; 3) Phase 2 dose expansion as a monotherapy once the RP2D has been determined; 4) Phase 2 dose expansion in combination with nivolumab; 5) Phase 1 monotherapy dose confirmation in patients with renal insufficiency once the monotherapy RP2D has been determined

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must have locally advanced or metastatic disease that is refractory to standard therapy, or for which no standard therapy is judged to be appropriate or provide clinical benefit, as judged by the Investigator
• Must have a histologically or cytologically confirmed malignant solid tumor associated with Nectin-4 expression, including, but not limited to, urothelial (transitional cell) carcinoma; head and neck squamous cell carcinoma; non-small cell lung cancer; and ovarian, breast, gastric, or esophageal carcinoma
• Must have ECOG performance status score 0 or 1 and acceptable organ and hematological function
• Must have metastatic or locally advanced disease and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Life expectancy =12 weeks
• Must submit fresh or archival tumor tissue
• Must provide written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analysis

Exclusion Criteria:

• Prior therapy with a cytotoxic, small molecule, or other systemic chemotherapy within 14 days of the first dose of study drug
• Prior immunotherapy, including monoclonal antibodies, within 28 days or 5 half-lives of the first dose of study drug, whichever is shorter
• Prior treatment with CD137 targeted therapy
• Mean resting QTc (eg, QTcF) greater than 470 msec on triplicate electrocardiograms (ECGs) obtained at screening
• Uncontrolled symptomatic brain metastases
• Uncontrolled diabetes with glycosylated hemoglobin greater than or equal to 8%
• Uncontrolled hypertension at screening or prior to initiation of study drug
• History of autoimmune disease except well-controlled diabetes mellitus, alopecia, well controlled thyroid disease or vitiligo

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• BT7480
Participants will receive a 60 minute IV infusion of BT7480 once weekly (i.e., on Days 1,8,15 and 22) during a 28-day cycle
• Nivolumab
Nivolumab will be given as a 240mg dose every 2 weeks administered as per local labelling as a 30 minute IV infusion

Locations

Country	Name	City	State
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	Surrey
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	State University of Iowa	Iowa City	Iowa
United States	Columbia University Irving Medical Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	START Center for Cancer Care	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
BicycleTx Limited

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with treatment emergent adverse events in dose escalation phase	Incidence and severity of treatment emergent adverse events to assess safety and tolerability following treatment with BT7480 alone and in patients with renal insufficiency using NCI CTCAE v5.0 criteria	From Cycle 1 Day 1 (each cycle is 28 days) until 30 (+/-5) days after the last dose of study drug
Primary	Number of patients with treatment emergent adverse events in dose escalation phase	Incidence and severity of treatment emergent adverse events to assess safety and tolerability following treatment with BT7480 and in combination with nivolumab using NCI CTCAE v5.0 criteria	From Cycle 1 Day 1 (each cycle is 28 days) until 125 (+/-5) days after the last dose of study drug
Primary	Confirmed response rate as measured by overall response rate (ORR) to demonstrate clinical activity following treatment with BT7480 in dose expansion phase	Overall response rate (ORR) following treatment with BT7480 alone and in combination with nivolumab according to RECIST 1.1 criteria nivolumab according to RECIST 1.1 criteria	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Primary	Confirmed response rate as measured by clinical benefit rate (CBR) to demonstrate clinical activity following treatment with BT7480 in dose expansion phase	Clinical benefit rate (CBR) following treatment with BT7480 alone and in combination with nivolumab according to RECIST 1.1 criteria nivolumab according to RECIST 1.1 criteria	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Secondary	Confirmed response rate as measured by overall response rate (ORR) to demonstrate clinical activity following treatment with BT7480 in dose escalation phase	Overall response rate (ORR) following treatment with BT7480 alone and in combination with nivolumab and in patients with renal insufficiency according to RECIST 1.1 criteria	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Secondary	Confirmed response rate as measured by clinical benefit rate (CBR) to demonstrate clinical activity following treatment with BT7480 in dose escalation phase	Clinical benefit rate (CBR) following treatment with BT7480 alone and in combination with nivolumab and in patients with renal insufficiency according to RECIST 1.1 criteria	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Secondary	Number of patients with treatment emergent adverse events in dose expansion phase	Incidence and severity of treatment emergent adverse events to assess safety and tolerability following treatment with BT7480 alone using NCI CTCAE v5.0 criteria	From Cycle 1 Day 1 (each cycle is 28 days) until 30 (+/-5) days after the last dose of study drug
Secondary	Number of patients with treatment emergent adverse events in dose expansion phase	Incidence and severity of treatment emergent adverse events to assess safety and tolerability following treatment with BT7480 alone using NCI CTCAE v5.0 criteria	From Cycle 1 Day 1 (each cycle is 28 days) until 125 (+/-5) days after the last dose of study drug
Secondary	Duration of response to assess clinical activity in dose escalation and dose expansion phase	Duration of response following treatment with BT7480 alone and in combination with nivolumab and in patients with renal insufficiency	From initial response to therapy to subsequent disease progression, an average of 6 months
Secondary	Progression free survival time in dose escalation and dose expansion phase	Duration of time from first drug administration to disease progression according to RECIST 1.1 following treatment with BT7480 alone and in combination with nivolumab and in patients with renal insufficiency	At 6 months
Secondary	Maximum plasma concentration (Cmax) of BT7480	Maximum plasma concentration (Cmax) of BT7480 in all participants receiving BT7480 alone or in combination with nivolumab	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Secondary	Area under the plasma concentration-time curve (AUC) of BT7480	Area under the plasma concentration-time curve (AUC) of BT7480 in all participants receiving BT7480 alone or in combination with nivolumab	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Secondary	Terminal half life (t1/2) of BT7480 in plasma	Terminal half life (t1/2) of BT7480 in plasma in all participants receiving BT7480 alone or in combination with nivolumab	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Secondary	Cumulative amount of BT7480 excreted in the urine	Cumulative amount of BT7480 excreted in the urine in all participants receiving BT7480 alone or in combination with nivolumab	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Secondary	Number of participants positive for anti-drug antibodies (ADA)	Incidence of ADAs in patients treated with BT7480 alone or in combination with nivolumab	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Secondary	Level of CD137 target engagement in all patients	Level of CD137 target engagement in peripheral blood in patients treated with BT7480 alone or in combination with nivolumab	From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months