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

Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT5528 in Patients With Advanced Malignancies Associated With EphA2 Expression

INTRODUCTION

  • Org Study ID: BT5528-100
  • Secondary ID: N/A
  • NTC ID: NCT04180371
  • Sponsor: Bicycle Tx Limited

BRIEF SUMMARY


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.


  • Overall Status
    Recruiting
  • Start Date
    November 7, 2019
  • Phase
    Phase 1/Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Phase I: Number of participants receiving BT5528 alone and in combination with nivolumab with treatment-emergent adverse events

Primary Outcome 1 - Timeframe: From Cycle 1 Day 1 (each cycle is 28 days) until 30 days post last dose

Primary Outcome 2 - Measure: Phase I: Maximum tolerated dose (MTD) by the number of participants with dose limiting toxicities from BT5528 treatment alone and in combination with nivolumab

Primary Outcome 2 - Timeframe: At the end of Cycle 1 (each cycle is 28 days)

Primary Outcome 3 - Measure: Phase II: Objective response rate by RECIST 1.1 in participants with selected solid tumor indications receiving BT5528 treatment alone and in combination with nivolumab

Primary Outcome 3 - Timeframe: 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)

Primary Outcome 4 - Measure: Phase II: Duration of response by RECIST 1.1 in participants with selected solid tumor indications receiving BT5528 treatment alone and in combination with nivolumab

Primary Outcome 4 - Timeframe: 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

Primary Outcome 5 - Measure: Phase II: Clinical benefit rate by RECIST 1.1 in participants with selected solid tumor indications receiving BT5528 treatment alone and in combination with nivolumab

Primary Outcome 5 - Timeframe: 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

Primary Outcome 6 - Measure: Phase II: Time to tumor progression by RECIST 1.1 in participants with selected solid tumor indications receiving BT5528 treatment alone and in combination with nivolumab

Primary Outcome 6 - Timeframe: 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

Primary Outcome 7 - Measure: Phase II: Progression free survival by RECIST 1.1 in participants with selected solid tumor indications receiving BT5528 treatment alone and in combination with nivolumab

Primary Outcome 7 - Timeframe: 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

Primary Outcome 8 - Measure: Phase II: Progression free survival at 6 months by RECIST 1.1 in participants with selected solid tumor indications receiving BT5528 treatment alone and in combination with nivolumab

Primary Outcome 8 - Timeframe: 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)

Primary Outcome 9 - Measure: Phase II: Overall survival at 1 year in participants with selected solid tumor indications receiving BT5528 treatment alone and in combination with nivolumab

Primary Outcome 9 - Timeframe: 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 for up to 1 year)

CONDITION

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

ELIGIBILITY


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

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Johanna Bendell

Role: Study Chair

Affiliation: Tennessee Oncology

Overall Contact

Name: Johanna Bendell

Phone: 617-945-8155

Email: clinicalstudies@bicycletx.com

LOCATION

Facility Status Contact
Facility: Florida Cancer Specialists
Sarasota, Florida 34232
United States
Status: Recruiting Contact:
Judy Wang, MD

Facility: Stephenson Cancer Center (Oklahoma University)
Oklahoma City, Oklahoma 73104
United States
Status: Recruiting Contact:
Debra Richardson, MD

Facility: Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania 19107
United States
Status: Recruiting Contact:
Babar Bashir, MD

Facility: Tennessee Oncology, PLLC
Nashville, Tennessee 37203
United States
Status: Recruiting Contact:
Johanna Bendell, MD