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
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 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
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 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
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
Name: Meredith McKean, MD, MPH
Role: Study Chair
Affiliation: Tennessee Oncology, PLLC
Name: Bicycle Tx Limited
Phone: 617-945-8155
Email: clinicalstudies@bicycletx.com