Clinical Trials /

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

NCT04561362

Description:

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

Related Conditions:
  • Breast Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT04561362

Trial Eligibility

Document

Title

  • Brief Title: Study BT8009-100 in Subjects With Nectin-4 Expressing Advanced Solid Tumors Malignancies
  • Official Title: Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: BT8009-100
  • NCT ID: NCT04561362

Conditions

  • Advanced Solid Tumor
  • Urinary Bladder Neoplasm
  • Pancreatic Neoplasms
  • Triple Negative Breast Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Stomach Neoplasm
  • Esophageal Neoplasms
  • Ovarian Neoplasm

Interventions

DrugSynonymsArms
BT8009Cohort A-1 BT8009 Monotherapy Dose Escalation
NivolumabOpdivoCohort A-2 BT8009 and Nivolumab Dose Escalation

Purpose

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

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort A-1 BT8009 Monotherapy Dose EscalationExperimentalParticipants will receive increasing doses of BT8009. It is expected that approximately 34 participants will participate in this dose escalation arm.
  • BT8009
Cohort A-2 BT8009 and Nivolumab Dose EscalationExperimentalParticipants 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
  • BT8009
  • Nivolumab
Cohort B-1 - Dose expansion (BT8009 alone)ExperimentalParticipants will receive a selected dose of BT8009. It is expected that approximately 40 participants will participate in this dose expansion arm
  • BT8009
Cohort B-2 - Dose expansion (BT8009 and nivolumab)ExperimentalParticipants 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.
  • BT8009
  • Nivolumab
Cohort C - Renal Insufficiency (BT8009 alone)ExperimentalParticipants will receive a selected dose of BT8009. It is expected that approximately 12 participants will participate in this arm.
  • BT8009

Eligibility 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.

          -  Part A cohorts: patients with advanced, histologically confirmed malignant solid
             tumors that recurred after or have been refractory to previous therapy:

               1. urothelial (transitional cell) carcinoma (fresh biopsy or an archived sample must
                  be submitted); or

               2. having pancreatic, breast, non-small-cell lung cancer (NSCLC), gastric,
                  esophageal, head and neck, or ovarian tumor tissue 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)

          -  Prior treatment with Nectin-4 targeted therapy

          -  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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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 Issue:
Description:Safety reported as incidence of treatment-emergent adverse events using CTCAE v5.0 criteria.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure: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)
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with nivolumab
Measure: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
Safety Issue:
Description:Number of participants positive for anti-drug antibodies (ADA) from all participants receiving BT8009 alone and in combination with nivolumab

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bicycle Tx Limited

Trial Keywords

  • nectin-4
  • solid tumor
  • transitional urothelial carcinoma
  • renal insufficiency

Last Updated

August 11, 2021