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

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

INTRODUCTION

  • Org Study ID: BT8009-100
  • Secondary ID: N/A
  • NTC ID: NCT04561362
  • Sponsor: 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.

  • Overall Status
    Recruiting
  • Start Date
    July 17, 2020
  • Phase
    Phase 1, Phase 2
  • Study Type
    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 - Timeframe: 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 - Timeframe: 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 - Timeframe: 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 - Timeframe: 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 - Timeframe: 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 - Timeframe: 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 - Timeframe: 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 - Timeframe: 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 - Timeframe: 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

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

- 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

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: Meredith McKean, MD, MPH

Phone: 617-945-8155

Email: clinicalstudies@bicycletx.com

LOCATION

Facility Status Contact
Facility: Sarah Cannon Research Institute at HealthONE
Denver, Colorado 80218
United States
Status: Recruiting Contact: Principal Investigator
Gerald Falchook, MD

Facility: Ocala Oncology Center
Ocala, Florida 34474
United States
Status: Recruiting Contact: Principal Investigator
Rama Balaraman, MD

Facility: Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada 89169
United States
Status: Recruiting Contact: Principal Investigator
Fadi Braiteh, MD

Facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania 19107
United States
Status: Recruiting Contact: Principal Investigator
Neil Palmisiano, MD

Facility: Tennessee Oncology, PLLC
Nashville, Tennessee 37203
United States
Status: Recruiting Contact: Contact
Meredith McKean, MD, MPH

Facility: Cross Cancer Institute
Edmonton, Alberta T6G 1Z2
Canada
Status: Recruiting Contact: Principal Investigator
Quincy Siu Chung Chu, MD

Facility: Institut Bergonie
Bordeaux, 33076
France
Status: Recruiting Contact: Principal Investigator
Antoine Italiano, MD, PhD

Facility: Institut Gustave Roussy
Villejuif, 94805
France
Status: Recruiting Contact: Principal Investigator
Capucine Baldini, MD

Facility: Ospedale San Raffaele
Milan, 20132
Italy
Status: Recruiting Contact: Principal Investigator
Andrea Necchi, MD

Facility: Vall d'Hebron Institute of Oncology
Barcelona, 08035
Spain
Status: Recruiting Contact: Principal Investigator
Irene Brana, MD, PhD

Facility: Hospital Clinic de Barcelona
Barcelona, 08036
Spain
Status: Recruiting Contact: Principal Investigator
Oscar Reig, MD

Facility: START Madrid Fundacion Jimenez Diaz
Madrid, 28040
Spain
Status: Recruiting Contact: Principal Investigator
Bernard Doger, MD, PhD

Facility: Sarah Cannon Research Institute UK
London, W1G 6AD
United Kingdom
Status: Recruiting Contact: Principal Investigator
Hendrik-Tobias Arkenau, MD

Facility: The Christie NHS Foundation Trust
Manchester, M20 4BX
United Kingdom
Status: Recruiting Contact: Principal Investigator
Louise Carter, MBBS, PhD