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Study BT8009-100 in Subjects With Nectin-4 Expressing Advanced Solid Tumors Malignancies

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ClinicalTrials.gov Identifier: NCT04561362
Recruitment Status : Recruiting
First Posted : September 23, 2020
Last Update Posted : February 16, 2022
Sponsor:
Information provided by (Responsible Party):
BicycleTx Limited

Study Description
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Brief Summary:

This clinical trial is evaluating a drug called BT8009 alone and in combination with nivolumab in participants with advanced solid tumors associated with Nectin-4 expression or in participants with advanced solid tumor malignancies having renal insufficiency.

The main goals of this study are to:

  • Find the recommended dose of BT8009 that can be given safely to participants alone and in combination with nivolumab
  • Learn more about the side effects and effectiveness of BT8009 alone and in combination with nivolumab
  • Learn more about BT8009 alone and in combination with nivolumab
  • Learn more about BT8009 alone in patients with kidney disease

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Urinary Bladder Neoplasm Pancreatic Neoplasms Triple Negative Breast Neoplasms Carcinoma, Non-Small-Cell Lung Stomach Neoplasm Esophageal Neoplasms Ovarian Neoplasm Drug: BT8009 Drug: Nivolumab Phase 1 Phase 2

Detailed Description:

BT8009 consists of a Bicycle peptide (Bicycle®) which binds selectively to Nectin-4, and is covalently attached to a spacer and a cleavable linker attached to a cytotoxin (MMAE).

This study is a Phase I/II, multicenter, first-in-human, open-label dose-escalation study of BT8009 given as a single agent given once weekly and in combination with nivolumab. There are three parts to this study. Part A is a dose escalation in patients with select advanced solid tumors primarily designed to evaluate safety and tolerability of BT8009 as monotherapy or in combination with nivolumab and to determine a recommended Phase II dose (RP2D). Following a selection of a recommended Phase II dose (RP2D), part B, a dose expansion portion, will be initiated with the primary objective of clinical activity of BT8009 as a monotherapy or in combination with nivolumab in patients with select advanced solid tumors. Part C will evaluate safety and tolerability of chosen RP2D of BT8009 in patients with renal insufficiency.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 172 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies
Actual Study Start Date : July 17, 2020
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort A-1 BT8009 Monotherapy Dose Escalation
Participants will receive increasing doses of BT8009. It is expected that approximately 60 participants will participate in this dose escalation arm.
 Drug: BT8009
Participants will receive a 60-minute IV infusion of BT8009 once weekly (i.e., on Days 1, 8, and 15, and 22) on a 28-day cycle.
Experimental: Cohort A-2 BT8009 and Nivolumab Dose Escalation
Participants will receive increasing doses of BT8009 and a standard dose of nivolumab. It is expected that approximately 20 participants will participate in this dose escalation arm
 Drug: BT8009
Participants will receive a 60-minute IV infusion of BT8009 once weekly (i.e., on Days 1, 8, and 15, and 22) on a 28-day cycle.

Drug: Nivolumab
Nivolumab will be a 240 mg dose every 2 weeks administered as per local labeling as a 30 minute intravenous infusion (window of -5 to +15 minutes).
Other Name: Opdivo
Experimental: Cohort B-1 - Dose expansion (BT8009 alone)
Participants will receive a selected dose of BT8009. It is expected that approximately 40 participants will participate in this dose expansion arm
 Drug: BT8009
Participants will receive a 60-minute IV infusion of BT8009 once weekly (i.e., on Days 1, 8, and 15, and 22) on a 28-day cycle.
Experimental: Cohort B-2 - Dose expansion (BT8009 and nivolumab)
Participants will receive a selected dose of BT8009 and a standard dose of nivolumab. It is expected that approximately 40 participants will participate in this dose expansion arm.
 Drug: BT8009
Participants will receive a 60-minute IV infusion of BT8009 once weekly (i.e., on Days 1, 8, and 15, and 22) on a 28-day cycle.

Drug: Nivolumab
Nivolumab will be a 240 mg dose every 2 weeks administered as per local labeling as a 30 minute intravenous infusion (window of -5 to +15 minutes).
Other Name: Opdivo
Experimental: Cohort C - Renal Insufficiency (BT8009 alone)
Participants will receive a selected dose of BT8009. It is expected that approximately 12 participants will participate in this arm.
 Drug: BT8009
Participants will receive a 60-minute IV infusion of BT8009 once weekly (i.e., on Days 1, 8, and 15, and 22) on a 28-day cycle.


Outcome Measures
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Primary Outcome Measures :
  1. Cohorts A-1, A-2 and C: Number of participants with treatment emergent adverse events receiving BT8009 alone and in combination with nivolumab to assess safety and tolerability [ Time Frame: From cycle 1 day 1 until 30 days after the end of treatment (each cycle is 28 days) ]
    Safety reported as incidence of treatment-emergent adverse events using CTCAE v5.0 criteria.

  2. Cohort A-1 and A-2 (escalations): Number of participants with dose limiting toxicities on BT8009 alone and in combination with nivolumab [ Time Frame: From cycle 1 day 1 to the end of cycle 1 (each cycle is 28 days) ]
    Number of patients who experience dose limiting toxicities BT8009 when given as a monotherapy and in combination with nivolumab.

  3. Cohort B-1 and B-2 (expansions): Objective response rate (ORR) to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or death or up to three years ]
    Proportion of participants with select solid tumors with confirmed complete response or partial response to BT8009 as a monotherapy and in combination with nivolumab according to RECIST 1.1 criteria

  4. Cohort B-1 and B-2 (expansions): Duration of response to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or death or up to three years ]
    Duration of response in participants with selected solid tumor indications receiving BT8009 treatment alone and in combination with nivolumab

  5. Cohort B-1 and B-2 (expansions): Clinical benefit rate to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or death or up to three years ]
    Proportion of participants with select solid tumors indications who have complete response (CR), partial response (PR) or stable disease (SD) for more than 6 weeks according to the RECIST Version 1.1 criteria.

  6. Cohort B-1 and B-2 (expansions): Time to tumor progression to assess the clinical activity of BT8009 as a monotherapy and in combination [ Time Frame: Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or death or up to 3 years ]
    Duration of time from start of study administration until disease progression according to RECIST 1.1 in participants with select solid tumor indications receiving BT8009 treatment alone and in combination with nivolumab

  7. Cohort B-1 and B-2 (expansions): Progression free survival time to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to three years ]
    Duration of time from the first day of study drug administration (Day 1) to disease progression according to RECIST 1.1 criteria in participants receiving BT8009 treatment alone and in combination with nivolumab

  8. Cohort B-1 and B-2 (expansions): Progression free survival rate at 6 months to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab using RECIST 1.1 [ Time Frame: Every 8 weeks after cycle 1 day 1 for 6 months (each cycle is 28 days) ]
    Proportion of participants receiving BT8009 as monotherapy and in combination with nivolumab and without disease progression at 6 months from the start of study drug administration according to RECIST 1.1 criteria

  9. Cohort B-1 and B-2 (expansions): Overall survival rate at 12 months to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab using RECIST 1.1 [ Time Frame: Every 3 months for up to 1 year ]
    Proportion of participants receiving BT8009 as monotherapy and in combination with nivolumab who experience death within 1 year from start of study drug administration.


Secondary Outcome Measures :
  1. Part A-1 and A-2 and C: Objective response rate to assess preliminary anti-tumor activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death or up to three years ]
    Proportion of participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency with confirmed complete response or partial response according to RECIST 1.1 criteria

  2. Cohort A-1 and A-2 and C: Duration of Response time to assess preliminary anti-tumor activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death or up to three years ]
    Duration of response by RECIST 1.1 in participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 treatment alone and in combination with nivolumab

  3. Cohort A-1 and A-2 and C: Clinical benefit rate to assess preliminary anti-tumor activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks for the first 12 months then every 12 weeks until disease progression for up to 3 years ]
    Proportion of participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency who have complete response (CR), partial response (PR) or stable disease (SD) for more than 6 weeks according to the RECIST Version 1.1 criteria.

  4. Cohort A-1 and A-2 and C: Time to progression to assess preliminary anti-tumor activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to 3 years ]
    Duration of time from start of study administration until disease progression according to RECIST 1.1 in participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 treatment alone and in combination with nivolumab

  5. Cohort A-1 and A-2 and C: Progression free survival time to assess preliminary anti-tumor activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to three years ]
    Duration of time from start of study administration until disease progression according to RECIST 1.1 in participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 treatment alone and in combination with nivolumab

  6. Cohort A-1 and A-2 and C: Progression free survival rate at 6 months to assess preliminary anti-tumor activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 8 weeks after cycle 1 day 1 for 6 months (each cycle is 28 days) ]
    Proportion of participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 as monotherapy and in combination with nivolumab and without disease progression at 6 months from the start of study drug administration according to RECIST 1.1 criteria

  7. Cohort A-1 and A-2 and C: Overall survival rate to assess preliminary anti-tumor activity of BT8009 as a monotherapy and in combination with nivolumab [ Time Frame: Every 3 months for up to 1 year ]
    Proportion of participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 as monotherapy and in combination with nivolumab who experience death within 1 year from start of study drug administration.

  8. Cohort B1 and B2 (expansion): Number of participants with treatment emergent adverse events receiving BT8009 alone and in combination with nivolumab to assess safety and tolerability [ Time Frame: From cycle 1 day 1 until 30 days after the end of treatment (each cycle is 28 days) or approximately 1 year ]
    Number of participants with advanced solid tumor malignancies associated with Nectin-4 expression receiving BT8009 alone or in combination with nivolumab who experience treatment-emergent adverse events using CTCAE v5.0 criteria.

  9. All cohorts: Plasma concentrations of BT8009 and MMAE to determine its PK parameters [ Time Frame: From Cycle 1 Day 1 through end of treatment (each cycle is 28 days) or for up to 1 year ]
    Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with nivolumab

  10. All cohorts: Number of participants positive for anti-drug antibodies (ADA) to determine incidence of ADA [ Time Frame: From Cycle 1 Day 1 through end of treatment (each cycle is 28 days) or for up to 1 year ]
    Number of participants positive for anti-drug antibodies (ADA) from all participants receiving BT8009 alone and in combination with nivolumab


Eligibility Criteria
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Information from the National Library of Medicine

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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

Key Inclusion Criteria

  • Life expectancy ≥12 weeks
  • Must have exhausted all standard treatment options, including appropriate targeted therapies, for example, EGFR or ALK therapies for relevant oncogene driver NSCLC patients; or available MMAE-containing ADC treatment in urothelial carcinoma; or patients for which no standard therapy is considered appropriate or to provide clinical benefit, as assessed by the Investigator.

  • Part A cohorts: Patients with the following tumor histology:

    1. patients with advanced, histologically confirmed urothelial (transitional cell) carcinoma that recurred after or has been refractory to prior therapy (fresh tumor biopsy or an archived sample must be submitted); or
    2. Patients with advanced, histologically confirmed pancreatic, breast, non-small-cell lung cancer (NSCLC), gastric, esophageal, head and neck, or ovarian tumor that recurred after or has been refractory to prior therapy (fresh tumor biopsy or an archived sample testing positive for Nectin-4 expression)
  • Part B-1 and B-2 Nectin-4 basket monotherapy and combination cohorts: patients with solid tumor advanced, recurrent disease confirmed as Nectin-4 positive who must have failed at least one prior line of therapy and radiologically progressed on most recent line of therapy.
  • Part C renal insufficiency cohort: Patients with solid tumor, advanced disease who have renal insufficiency.

Key Exclusion Criteria (all patients)

  • Clinically relevant troponin elevation
  • Uncontrolled diabetes
  • Uncontrolled, symptomatic brain metastases
  • Patients with uncontrolled hypertension
  • History of another malignancy within 3 years before first dose of BT8009 or residual disease from a previously diagnosed malignancy (with some exceptions).
  • Systemic IV anti-infective treatment, or fever within the last 14 days prior to first dose of BT8009.

Parts A-2 and B-2 Nivolumab Combination Cohorts Exclusion Criteria

  • Prior organ transplant (including allogeneic)
  • Active systemic infection requiring therapy
  • History of interstitial lung disease

Other protocol-defined Inclusion/Exclusion criteria may apply

Contacts and Locations
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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): NCT04561362


Contacts
Layout table for location contacts
Contact: Bicycle Tx Limited 617-945-8155 clinicalstudies@bicycletx.com

Locations
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Sponsors and Collaborators
BicycleTx Limited
Investigators
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Study Chair: Meredith McKean, MD, MPH Tennessee Oncology, PLLC
More Information
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Responsible Party: BicycleTx Limited
ClinicalTrials.gov Identifier: NCT04561362    
Other Study ID Numbers: BT8009-100
First Posted: September 23, 2020    Key Record Dates
Last Update Posted: February 16, 2022
Last Verified: February 2022

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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:
nectin-4
solid tumor
transitional urothelial carcinoma
renal insufficiency
Additional relevant MeSH terms:
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Neoplasms
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Ovarian Neoplasms
Stomach Neoplasms
Esophageal Neoplasms
Urinary Bladder Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
 Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Gonadal Disorders
Gastrointestinal Neoplasms