Clinical trial NCT05163041: Study BT7480-100 in Patients With Advanced Malignancies Associated With Nectin-4 Expression
Official title: Phase 1/2 Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT7480 in Patients With Nectin-4 Associated Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Keywords: Advanced Solid Tumor
Lead sponsor: BicycleTx Limited
Sponsor class: INDUSTRY
First posted: 2021-12-20
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with treatment emergent adverse events in dose escalation phase
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) until 30 (+/-5) days after the last dose of study drug
measure: Number of patients with treatment emergent adverse events in dose escalation phase
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) until 125 (+/-5) days after the last dose of study drug
measure: Confirmed response rate as measured by overall response rate (ORR) to demonstrate clinical activity following treatment with BT7480 in dose expansion phase
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
measure: Confirmed response rate as measured by clinical benefit rate (CBR) to demonstrate clinical activity following treatment with BT7480 in dose expansion phase
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Secondary outcomes:
measure: Confirmed response rate as measured by overall response rate (ORR) to demonstrate clinical activity following treatment with BT7480 in dose escalation phase
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
measure: Confirmed response rate as measured by clinical benefit rate (CBR) to demonstrate clinical activity following treatment with BT7480 in dose escalation phase
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
measure: Number of patients with treatment emergent adverse events in dose expansion phase
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) until 30 (+/-5) days after the last dose of study drug
measure: Number of patients with treatment emergent adverse events in dose expansion phase
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) until 125 (+/-5) days after the last dose of study drug
measure: Duration of response to assess clinical activity in dose escalation and dose expansion phase
timeFrame: From initial response to therapy to subsequent disease progression, an average of 6 months
measure: Progression free survival time in dose escalation and dose expansion phase
timeFrame: At 6 months
measure: Maximum plasma concentration (Cmax) of BT7480
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
measure: Area under the plasma concentration-time curve (AUC) of BT7480
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
measure: Terminal half life (t1/2) of BT7480 in plasma
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
measure: Cumulative amount of BT7480 excreted in the urine
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
measure: Number of participants positive for anti-drug antibodies (ADA)
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
measure: Level of CD137 target engagement in all patients
timeFrame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: State University of Iowa
state: Iowa
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: START Center for Cancer Care
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
Study officials:
References: