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

NCT05163041 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BT7480-100
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 9

Brief 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

Conditions

Advanced Solid Tumor

Keywords

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (12)

• Confirmed response rate as measured by overall response rate (ORR) to demonstrate clinical activity following treatment with BT7480 in dose escalation phase

  From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months

• Confirmed response rate as measured by clinical benefit rate (CBR) to demonstrate clinical activity following treatment with BT7480 in dose escalation phase

  From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months

• Number of patients with treatment emergent adverse events in dose expansion phase

  From Cycle 1 Day 1 (each cycle is 28 days) until 30 (+/-5) days after the last dose of study drug

• Number of patients with treatment emergent adverse events in dose expansion phase

  From Cycle 1 Day 1 (each cycle is 28 days) until 125 (+/-5) days after the last dose of study drug

• Duration of response to assess clinical activity in dose escalation and dose expansion phase

  From initial response to therapy to subsequent disease progression, an average of 6 months

Study Arms (5)

BT7480 monotherapy dose escalation

EXPERIMENTAL

Participants will receive increasing doses of BT7480. It is expected that approximately 80 patients will participate in this dose escalation arm.

Drug: BT7480

BT7480 and nivolumab dose escalation

EXPERIMENTAL

Participants will receive increasing doses of BT7480 and standard dose of nivolumab. It is expected that approximately 12 patients will participate in this dose escalation arm.

Drug: BT7480; Drug: Nivolumab

BT7480 monotherapy dose expansion

EXPERIMENTAL

Participants will receive a selected dose of BT7480. It is expected that approximately 45 patients will participate in this dose expansion arm in Phase 2.

Drug: BT7480

BT7480 and nivolumab dose expansion

EXPERIMENTAL

Participants will receive a selected dose of BT7480 and standard dose of nivolumab. It is expected that approximately 45 patients will participate in this dose expansion arm in Phase 2.

Drug: BT7480; Drug: Nivolumab

BT7480 monotherapy in patients with renal insufficiency

EXPERIMENTAL

Participants will receive a selected dose of BT7480. It is expected that approximately 12 patients will participate in this dose confirmation arm.

Drug: BT7480

Interventions

BT7480 DRUG

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

BT7480 and nivolumab dose escalation; BT7480 and nivolumab dose expansion; BT7480 monotherapy dose escalation; BT7480 monotherapy dose expansion; BT7480 monotherapy in patients with renal insufficiency

Nivolumab DRUG

Nivolumab will be given as a 240mg dose every 2 weeks administered as per local labelling as a 30 minute IV infusion

BT7480 and nivolumab dose escalation; BT7480 and nivolumab dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BicycleTx Limited: lead

Study Sites (9)

State University of Iowa

Iowa City, Iowa, 52242, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

START Center for Cancer Care

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 20, 2021
• Study Start: November 2, 2021
• Primary Completion: August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); GB (2)