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BRIEF TITLE: Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies

Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies


  • Org Study ID: BT8009-100
  • Secondary ID:
  • NCT ID: NCT04561362
  • NCT Alias:
  • Sponsor: Bicycle Tx Limited - Industry
  • Source: Bicycle Tx Limited

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

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.

Overal Status Start Date Phase Study Type
Recruiting July 17, 2020 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - 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

Primary Outcome 1 - Time Frame: From cycle 1 day 1 until 30 days after the end of treatment (each cycle is 28 days)

Primary Outcome 2 - Measure: Cohort A-1 and A-2 (escalations): Number of participants with dose limiting toxicities on BT8009 alone and in combination with nivolumab

Primary Outcome 2 - Time Frame: From cycle 1 day 1 to the end of cycle 1 (each cycle is 28 days)

Primary Outcome 3 - Measure: 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

Primary Outcome 3 - Time Frame: Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or death or up to three years

Primary Outcome 4 - Measure: 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

Primary Outcome 4 - Time Frame: Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or death or up to three years

Primary Outcome 5 - Measure: 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

Primary Outcome 5 - Time Frame: Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or death or up to three years

Primary Outcome 6 - Measure: Cohort B-1 and B-2 (expansions): Time to tumor progression to assess the clinical activity of BT8009 as a monotherapy and in combination

Primary Outcome 6 - Time Frame: Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or death or up to 3 years

Primary Outcome 7 - Measure: 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

Primary Outcome 7 - Time Frame: Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to three years

Primary Outcome 8 - Measure: 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

Primary Outcome 8 - Time Frame: Every 8 weeks after cycle 1 day 1 for 6 months (each cycle is 28 days)

Primary Outcome 9 - Measure: 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

Primary Outcome 9 - Time Frame: Every 3 months for up to 1 year

Condition:

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

Eligibility

Criteria:
Key Inclusion Criteria

- Life expectancy ≥12 weeks

- Part A cohorts: patients with advanced, histologically confirmed malignant solid
tumors as follows:

1. urothelial (transitional cell) carcinoma naïve to Nectin-4 directed therapies; or

2. having tumor tissue testing positive for Nectin-4 expression; or

3. solid tumors known to be historically associated with Nectin-4 as follows:
pancreatic, triple negative breast cancer, non-small cell lung cancer, gastric,
esophageal or ovarian cancers.

- Part B-1 and B-2 Nectin-4 basket monotherapy and combination cohorts: patients with
solid tumor advanced, recurrent disease confirmed to express Nectin-4 who are naïve to
Nectin-4 directed therapy, and have exhausted all standard treatment options and had
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
exhausted all appropriate standards of care options and also 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

- Patients 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
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Meredith McKean, MD, MPH

Role: Study Chair

Affiliation: Tennessee Oncology, PLLC

Overall Contact

Name: Bicycle Tx Limited

Phone: 617-945-8155

Email: clinicalstudies@bicycletx.com

Locations

Facility Status Contact
Sarah Cannon Research Institute at HealthONE
Denver, Colorado 80218
United States
Recruiting
Tennessee Oncology, PLLC
Nashville, Tennessee 37203
United States
Recruiting Meredith McKean, MD, MPH