Clinical Trials /

Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression

NCT04180371

Description:

This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors that are believed to be associated with EphA2 expression. The main goals of this study are to: - Find the recommended dose of BT5528 that can be given safely to participants alone and in combination with nivolumab - Learn more about the side effects of BT5528 - Learn more about BT5528 therapy alone and in combination with nivolumab.

Related Conditions:
  • Lung Adenocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression
  • Official Title: Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT5528 in Patients With Advanced Malignancies Associated With EphA2 Expression

Clinical Trial IDs

  • ORG STUDY ID: BT5528-100
  • NCT ID: NCT04180371

Conditions

  • Non Small Cell Lung Cancer
  • Ovarian Cancer
  • Triple Negative Breast Cancer
  • Gastric Cancer
  • Pancreatic Cancer
  • Urothelial Cancer

Interventions

DrugSynonymsArms
BT5528Phase I - Dose escalation (BT5528)
NivolumabOpdivoPhase I - Dose escalation combination (BT5528 & nivolumab)

Purpose

This clinical trial is evaluating a drug called BT5528 alone and in combination with nivolumab in participants with advanced solid tumors that are believed to be associated with EphA2 expression. The main goals of this study are to: - Find the recommended dose of BT5528 that can be given safely to participants alone and in combination with nivolumab - Learn more about the side effects of BT5528 - Learn more about BT5528 therapy alone and in combination with nivolumab.

Detailed Description

      BT5528 consists of a bicyclic peptide (Bicycle®) which binds to EphA2, and is covalently
      attached to a spacer and a protease cleavable peptide linker attached to MMAE.

      The Phase I/II multi-center, open-label trial will evaluate BT5528 administered once-weekly
      as a single agent and in combination with nivolumab. The Phase I portion is a dose escalation
      primarily designed to assess the safety and tolerability of BT5528 and to determine a
      recommended Phase II dose (RP2D). Following selection of a recommended Phase II dose (RP2D),
      a dose expansion portion will be initiated with the primary objective of evaluating the
      clinical activity of BT5528.
    

Trial Arms

NameTypeDescriptionInterventions
Phase I - Dose escalation (BT5528)ExperimentalCohorts of participants will receive increasing doses of BT5528. It is expected that up to 48 participants will participate in this dose escalation arm.
  • BT5528
Phase I - Dose escalation combination (BT5528 & nivolumab)ExperimentalCohorts of participants will receive increasing doses of BT5528 and a standard dose of nivolumab. It is expected that up to 24 participants will participate in this dose escalation combination arm.
  • BT5528
  • Nivolumab
Phase II - Dose expansion (BT5528)ExperimentalA cohort of non-small cell lung cancer participants will receive the selected dose of BT5528. It is expected that up to 40 participants will participate in this dose expansion arm.
  • BT5528
Phase II - Dose expansion combination (BT5528 & nivolumab)ExperimentalA cohort of non-small cell lung cancer participants will receive the selected dose of BT5528 in combination with a standard dose of nivolumab. It is expected that up to 40 participants will participate in this dose expansion arm.
  • BT5528
  • Nivolumab

Eligibility Criteria

        General Inclusion:

          -  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 analyses

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

          -  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

          -  Acceptable renal, hepatic, hematologic and coagulation functions

          -  Negative pregnancy test for women of childbearing potential

          -  Male participants with female partners of childbearing potential and female
             participants of childbearing potential are required to follow highly effective
             contraception

          -  Availability of archived tumor samples or willingness to provide fresh tumor biopsy
             during screening

        Additional inclusion criteria for Phase I (dose escalation phase, with BT5528 alone or in
        combination with nivolumab):

          -  Have advanced, histologically confirmed malignant solid tumors historically known for
             high expression of EphA2 that recurred after previous therapy and are candidates for a
             Phase I study due to lack of approved or standard options for treatment

        Additional inclusion criteria for Phase II (dose expansion phase, with BT5528 alone or in
        combination with nivolumab):

          -  Participants with metastatic recurrent disease histologically confirmed to be
             adenocarcinoma subtype of NSCLC (adeno-NSCLC) are eligible and must have exhausted all
             standard treatment options including progression on or after platinum-based
             chemotherapy

        Exclusion criteria (all participants):

          -  Chemotherapy treatments within 14 days prior to first dose of study treatment, other
             anticancer treatments, treatment within 28 days or 5 half-lives, whichever is the
             shorter

          -  Experimental treatments within 4 weeks of first dose of BT5528

          -  Current treatment with strong inhibitors or inducers of CYP3A4 or strong inhibitors of
             P-gp

          -  Uncontrolled, symptomatic brain metastases

          -  Any condition, therapy or laboratory abnormality that might confound the results of
             the study, interfere with the patient's participation, or is not in the best interest
             of the patient to participate in the opinion of the investigator including but not
             limited to specific cardiovascular criteria

          -  Thromboembolic events and/or bleeding disorders 3 months (e.g., deep vein thrombosis
             [DVT] or pulmonary embolism [PE]) prior to first dose

        Additional Exclusion Criteria (BT5528 in combination with nivolumab):

          -  Prior organ transplant (including allogeneic)

          -  Diagnosis of clinically relevant immunodeficiency

          -  Active systemic infection requiring therapy

          -  More than 10 mg daily prednisone equivalent or other strong immunosuppressant

          -  History of autoimmune disease except alopecia or vitiligo

          -  History of interstitial lung disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Number of participants receiving BT5528 alone and in combination with nivolumab with treatment-emergent adverse events
Time Frame:From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose
Safety Issue:
Description:Safety reported as incidence of treatment-emergent adverse events

Secondary Outcome Measures

Measure:Phase I: Objective response rate by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Safety Issue:
Description:Objective Response Rate (ORR)
Measure:Phase I: Duration of response by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Safety Issue:
Description:Duration of Response (DOR)
Measure:Phase I: Clinical benefit rate by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Safety Issue:
Description:Clinical benefit rate
Measure:Phase I: Time to tumor progression by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Safety Issue:
Description:Time to progression (TTP)
Measure:Phase I: Progression free survival time by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months then every 16 weeks up to 12 months
Safety Issue:
Description:Progression free survival (PFS)
Measure:Phase I: Progression free survival at 6 months by RECIST 1.1 in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1 Day 1 (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or loss of follow-up or withdrawal of consent (assessed every 8 weeks up to 6 months)
Safety Issue:
Description:Progression free survival (PFS)
Measure:Phase I: Overall survival time at 12 months in participants with advanced solid tumors with high EphA2 levels receiving BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1 Day 1 (each cycle is 28 days) until death or loss of follow-up or withdrawal of consent (assessed every 3 months up to 12 months
Safety Issue:
Description:Overall survival (OS)
Measure:Phase II: Determination of the number of participants with non-small cell lung cancer receiving BT5528 alone and in combination with nivolumab with treatment-emergent adverse events
Time Frame:From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose
Safety Issue:
Description:
Measure:All phases: Maximum observed plasma concentration (Cmax) of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months
Safety Issue:
Description:
Measure:All phases: Minimum observed plasma concentration (Cmin) of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months
Safety Issue:
Description:
Measure:All phases: Area under the plasma concentration versus time curve (AUC) of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months
Safety Issue:
Description:
Measure:All phases: Biological terminal half-life (t1/2) of BT5528 in plasma from all participants taking BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months
Safety Issue:
Description:
Measure:All phases: Number of participants positive for anti-drug antibodies (ADA) from all participants receiving BT5528 alone and in combination with nivolumab
Time Frame:From Cycle 1,and end of each cycle (each cycle is 28 days) until disease progression or death or new anti-cancer therapy or withdrawal of consent(assessed up to 12 months
Safety Issue:
Description:

Details

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

Trial Keywords

  • EphA2

Last Updated

November 26, 2019