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

Phase 2Active Not RecruitingNCT05163041

BicycleTx Limited200 enrolled

Overview

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

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

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

200

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: 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

Time frame: 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

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

Secondary Outcomes

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

Time frame: 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

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

Time frame: 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

Incidence and severity of treatment emergent adverse events to assess safety and tolerability following treatment with BT7480 alone using NCI CTCAE v5.0 criteria

Time frame: 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

Incidence and severity of treatment emergent adverse events to assess safety and tolerability following treatment with BT7480 alone using NCI CTCAE v5.0 criteria

Time frame: 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

Duration of response following treatment with BT7480 alone and in combination with nivolumab and in patients with renal insufficiency

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

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

Time frame: At 6 months

Maximum plasma concentration (Cmax) of BT7480

Maximum plasma concentration (Cmax) of BT7480 in all participants receiving BT7480 alone or in combination with nivolumab

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

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

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

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

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

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

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

Number of participants positive for anti-drug antibodies (ADA)

Incidence of ADAs in patients treated with BT7480 alone or in combination with nivolumab

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

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

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

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

Overview

Conditions

Interventions

Eligibility

Locations (9)

Outcomes

Primary Outcomes

Secondary Outcomes