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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05163041
Recruitment Status : Recruiting
First Posted : December 20, 2021
Last Update Posted : July 7, 2022
Sponsor:
Information provided by (Responsible Party):
BicycleTx Limited

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

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: BT7480 Drug: Nivolumab Phase 1 Phase 2

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 1 and Phase 2 dose expansion as a monotherapy once the RP2D has been determined; 4) Phase 1 and 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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT7480 in Patients With Nectin-4 Associated Advanced Malignancies
Actual Study Start Date : November 2, 2021
Estimated Primary Completion Date : September 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: BT7480 monotherapy dose escalation
Participants will receive increasing doses of BT7480. It is expected that approximately 40 patients will participate in this dose escalation arm.
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

Experimental: BT7480 and nivolumab dose escalation
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
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

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

Experimental: BT7480 monotherapy dose expansion
Participants will receive a selected dose of BT7480. It is expected that approximately 20 patients will participate in this dose expansion arm in Phase 1 plus an additional 45 patients in Phase 2.
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

Experimental: BT7480 and nivolumab dose expansion
Participants will receive a selected dose of BT7480 and standard dose of nivolumab. It is expected that approximately 20 patients will participate in this dose expansion arm in Phase 1 plus an additional 45 patients in Phase 2.
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

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

Experimental: BT7480 monotherapy in patients with renal insufficiency
Participants will receive a selected dose of BT7480. It is expected that approximately 12 patients will participate in this dose confirmation arm.
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




Primary Outcome Measures :
  1. Number of patients with treatment emergent adverse events in dose escalation phase [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) until 30 (+/-5) days after the last dose of study drug ]
    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

  2. Number of patients with treatment emergent adverse events in dose escalation phase [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) until 125 (+/-5) days after the last dose of study drug ]
    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

  3. Confirmed response rate as measured by overall response rate (ORR) to demonstrate clinical activity following treatment with BT7480 in dose expansion phase [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months ]
    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

  4. Confirmed response rate as measured by clinical benefit rate (CBR) to demonstrate clinical activity following treatment with BT7480 in dose expansion phase [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months ]
    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


Secondary Outcome Measures :
  1. Confirmed response rate as measured by overall response rate (ORR) to demonstrate clinical activity following treatment with BT7480 in dose escalation phase [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months ]
    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

  2. Confirmed response rate as measured by clinical benefit rate (CBR) to demonstrate clinical activity following treatment with BT7480 in dose escalation phase [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months ]
    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

  3. Number of patients with treatment emergent adverse events in dose expansion phase [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) until 30 (+/-5) days after the last dose of study drug ]
    Incidence and severity of treatment emergent adverse events to assess safety and tolerability following treatment with BT7480 alone using NCI CTCAE v5.0 criteria

  4. Number of patients with treatment emergent adverse events in dose expansion phase [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) until 125 (+/-5) days after the last dose of study drug ]
    Incidence and severity of treatment emergent adverse events to assess safety and tolerability following treatment with BT7480 alone using NCI CTCAE v5.0 criteria

  5. Duration of response to assess clinical activity in dose escalation and dose expansion phase [ Time Frame: From initial response to therapy to subsequent disease progression, an average of 6 months ]
    Duration of response following treatment with BT7480 alone and in combination with nivolumab and in patients with renal insufficiency

  6. Progression free survival time in dose escalation and dose expansion phase [ Time Frame: At 6 months ]
    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

  7. Maximum plasma concentration (Cmax) of BT7480 [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months ]
    Maximum plasma concentration (Cmax) of BT7480 in all participants receiving BT7480 alone or in combination with nivolumab

  8. Area under the plasma concentration-time curve (AUC) of BT7480 [ 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 in all participants receiving BT7480 alone or in combination with nivolumab

  9. Terminal half life (t1/2) of BT7480 in plasma [ 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 in all participants receiving BT7480 alone or in combination with nivolumab

  10. Cumulative amount of BT7480 excreted in the urine [ 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 in all participants receiving BT7480 alone or in combination with nivolumab

  11. Number of participants positive for anti-drug antibodies (ADA) [ Time Frame: From Cycle 1 Day 1 (each cycle is 28 days) through study completion, an average of 6 months ]
    Incidence of ADAs in patients treated with BT7480 alone or in combination with nivolumab

  12. Level of CD137 target engagement in all patients [ 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 peripheral blood in patients treated with BT7480 alone or in combination with nivolumab



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 radiographically documented metastatic or locally advanced 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
  • Body mass index greater than or equal to 35 kg/m2
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05163041


Contacts
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Contact: BicycleTx Limited 617-945-8155 clinicalstudies@bicycletx.com

Locations
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United States, Iowa
State University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Mohammed Milhem, MD         
Principal Investigator: Mohammed Milhem, MD         
United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Afshin Dowlati, MD         
Principal Investigator: Afshin Dowlati, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Matthew Zibelman, MD         
Principal Investigator: Matthew Zibelman, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Rodon Ahnert, MD         
Principal Investigator: Rodon Ahnert, MD         
START Center for Cancer Care Recruiting
San Antonio, Texas, United States, 78229
Contact: Kyriakos Papadopolous, MD         
Principal Investigator: Kyriakos Papadopolous, MD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Alexander Spira, MD         
Principal Investigator: Alexander Spira, MD         
United Kingdom
The Beatson West of Scotland Cancer Centre Recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Thomas J Evans, Professor         
Principal Investigator: Thomas J Evans, Professor         
Sponsors and Collaborators
BicycleTx Limited
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Responsible Party: BicycleTx Limited
ClinicalTrials.gov Identifier: NCT05163041    
Other Study ID Numbers: BT7480-100
First Posted: December 20, 2021    Key Record Dates
Last Update Posted: July 7, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BicycleTx Limited:
Advanced Solid Tumor
Additional relevant MeSH terms:
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Neoplasms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action