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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:
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| State University of Iowa | Iowa City | Iowa | 52242 | United States | ||
| Columbia University Irving Medical Center |
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| Nivolumab | Drug | Nivolumab will be given as a 240mg dose every 2 weeks administered as per local labelling as a 30 minute IV infusion |
|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| New York |
| New York |
| 10032 |
| United States |
| University Hospitals Cleveland Medical Center | Cleveland | Ohio | 44106 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| START Center for Cancer Care | San Antonio | Texas | 78229 | United States |
| Virginia Cancer Specialists | Fairfax | Virginia | 22031 | United States |
| The Royal Marsden NHS Foundation Trust | Sutton | Surrey | SM2 5PT | United Kingdom |
| The Beatson West of Scotland Cancer Centre | Glasgow | G12 0YN | United Kingdom |
| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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