Back to Clinical Trials

Brief Title: 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
  • NCT ID: NCT04561362
  • Sponsor: BicycleTx Limited

BRIEF SUMMARY

This clinical trial is evaluating a drug called BT8009 alone and in combination with pembrolizumab 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 pembrolizumab
* Learn more about the side effects and effectiveness of BT8009 alone and in combination with pembrolizumab
* Learn more about BT8009 alone and in combination with pembrolizumab
* Learn more about BT8009 alone in patients with renal insufficiency

DETAILED DESCRIPTION

BT8009 consists of a bicyclic peptide (Bicycle®) which binds selectively to Nectin-4 covalently attached to a spacer and a val-cit 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 in 3 different dosing schedules- weekly (28 day cycle), biweekly (28 day cycle) , dosing on day 1 and day 8 of a 3-weekly cycle and in combination with pembrolizumab. 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 pembrolizumab and to determine a recommended Phase II dose (RP2D). Following a selection of an 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 pembrolizumab in patients with select advanced solid tumors. Part C will evaluate safety and tolerability of RP2D 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 pembrolizumab to assess safety and tolerability

Primary Outcome 1 - Timeframe: From cycle 1 day 1 until at least 30 days after the end of treatment (each cycle is 21 or 28 days depending on the assigned dosing schedule)

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

Primary Outcome 2 - Timeframe: 28 days (for cycles that are either 21 or 28 days in length depending on dosing schedule assigned).

Primary Outcome 3 - Measure: Cohorts B-1, B-2, and B-3 (expansions): Objective response rate (ORR) to assess the clinical activity of BT8009 as a monotherapy in patients with urothelial cancer using RECIST 1.1.

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: Cohorts B-4, B-5, and B-6 (expansions): Objective response rate (ORR) to assess the clinical activity of BT8009 as a monotherapy in patients with selected solid tumor indications associated with Nectin-4 expression using RECIST 1.1.

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-7 (expansion): Objective response rate (ORR) to assess the clinical activity of BT8009 in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma in combination with pembrolizumab using RECIST 1.1.

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

CONDITION

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

ELIGIBILITY

Key Inclusion Criteria
* Life expectancy ≥12 weeks.

- * Patients must have measurable disease per RECIST 1.1.

- * Part A-1 cohorts:
* Must have exhausted all standard treatment options, including appropriate targeted therapies; or patients for which no standard therapy is considered appropriate

- * Patients with advanced, histologically confirmed urothelial (transitional cell) carcinoma that recurred after or has been refractory to prior therapy (fresh tumor biopsy or an archived sample must be submitted); or

- * Patients with advanced, histologically confirmed pancreatic, breast, non-small-cell lung cancer (NSCLC), gastric, esophageal, head and neck, or ovarian tumors that recurred after or has been refractory to prior therapy (fresh tumor biopsy or an archived sample testing for Nectin-4 expression).

- * Part A-2:
* Must have exhausted all standard treatment options, including appropriate targeted therapies; or patients for which no standard therapy is considered appropriate

- * Patients with advanced, histologically confirmed urothelial (transitional cell) carcinoma that recurred after or has been refractory to prior therapy

- * Cohort B-1: Histologically documented urothelial carcinoma, previously treated with enfortumab vedotin (EV). Patients with resectable, locally advanced urothelial carcinoma are ineligible. Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.

- * Cohort B-2 and B-3: Histologically documented urothelial carcinoma, not previously treated with enfortumab vedotin (EV). Patients with resectable, locally advanced urothelial carcinoma are ineligible. Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.

- * Cohort B-4: Histologically confirmed non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer that is Stage III or IV according to the International Federation of Gynecology and Obstetrics (FIGO) or tumor, node and metastasis staging criteria that recurred after or has been refractory to prior therapy.

- * Cohort B-5: Breast cancers that have been confirmed negative for estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2) (i.e., triple-negative) that have recurred after or has been refractory to prior therapy.

- * Cohort B-6: Histologically confirmed non-small cell lung cancer (NSCLC) with no actionable mutations, such as Epidermal Growth Factor Receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion oncogene, or ROS1 that recurred after or has been refractory to prior therapy.

- * Cohort B-7: Locally advanced or metastatic, histologically confirmed urothelial (transitional cell) carcinoma, ineligible for cisplatin, no prior systemic anticancer treatment for advanced urothelial carcinoma.

- * Cohort C renal insufficiency cohort: Patients with histologically documented urothelial carcinoma that recurred after or has been refractory to prior therapy.
Key Exclusion Criteria (all patients):
* 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).

- * Active systemic infection requiring therapy, or fever within the last 14 days prior to first dose of BT8009.

- * Prior Stevens-Johnson syndrome/toxic epidermal necrolysis on any MMAE-conjugated drug

- * Parts A-2 and B-7 Pembrolizumab Combination Cohorts:
* Prior organ transplant (including allogeneic)

- * Diagnosis of clinically relevant immunodeficiency

- * History of interstitial lung disease

- * Parts B-2 and B-3: Prior treatment with enfortumab vedotin
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: Horizon Oncology Research
Lafayette, Indiana 47905
United States
Status: Recruiting Contact: Principal Investigator
Costantine Albany, MD

Facility: Norton Cancer Institute, Downtown
Louisville, Kentucky 40202
United States
Status: Recruiting Contact: Principal Investigator
Jaspreet Singh Grewal, MD, PhD, MPH

Facility: University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106
United States
Status: Recruiting Contact: Principal Investigator
Jason Robert Brown, MD, PhD

Facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania 19107
United States
Status: Recruiting Contact: Principal Investigator
Sarah W. Gordon, DO

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

Facility: The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: Principal Investigator
Jordi Rodon Ahnert, MD, PhD

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

Facility: Princess Margaret Cancer Centre
Toronto, Ontario M5G IZ5
Canada
Status: Recruiting Contact: Principal Investigator
Aaron R. Hansen, MD

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

Facility: Centre Leon Berard
Lyon, 69373
France
Status: Recruiting Contact: Principal Investigator
Loic Verligue, MD

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: Next Oncology - Hospital Quironsalud Madrid
Madrid, 28223
Spain
Status: Recruiting Contact: Principal Investigator
Valentina Boni, MD

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