Study BT8009-230 in Participants With Locally Advanced or Metastatic Urothelial Cancer (Duravelo-2)

BicycleTx

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Metastatic Urothelial Cancer

Treatments: Drug: Pembrolizumab; Drug: BT8009; Drug: Avelumab; Drug: Gemcitabine + cisplatin Or carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT06225596

BT8009-230

2023-504231-41 (EudraCT Number)

U1111-1300-3791 (Other Identifier)

Details and patient eligibility

About

This is a global, multicenter, randomized, open-label study, with an adaptive design. The main objective of the study is to measure the efficacy and safety of BT8009 (zelenectide pevedotin) as monotherapy and in combination with pembrolizumab in participants with locally advanced or metastatic urothelial cancer (UC). The study includes a dose selection phase followed by an adaptive design continuation. The study is comprised of 2 cohorts. Cohort 1 will include participants who have not received any prior systemic therapy for locally advanced or metastatic UC and are eligible to receive platinum-based chemotherapy, whereas Cohort 2 will include participants who have received ≥ 1 prior systemic therapy for locally advanced or metastatic UC.

Enrollment: 956 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Life expectancy ≥ 12 weeks.

• Measurable disease as defined by RECIST v1.1.

• Histologically or cytologically confirmed locally advanced (unresectable) or metastatic UC of the renal pelvis, ureter, bladder, or urethra.

• Archival or fresh tumor tissue comprising muscle-invasive UC or locally advanced or metastatic UC should be available for submission to central laboratory.

• Negative pregnancy test for women of childbearing potential (WOCBP) (negative serum test at Screening and negative urine or serum test within 72 hours prior to the first dose).

• Cohort 1: Previously Untreated: Eligible to receive platinum-based chemotherapy (either cisplatin- or carboplatin-based chemotherapy based on Investigator decision.

• Cohort 1: Participants must not have received prior systemic therapy for locally advanced or metastatic UC with the following exceptions:

  1. Prior local intravesical chemotherapy, local surgery when full resection is not achieved, local immunotherapy, and radiotherapy are permitted if completed at least 4 weeks prior to the initiation of study treatment and all acute toxicities have resolved.
  2. Prior neoadjuvant/adjuvant chemotherapy or monomethyl auristatin E (MMAE)-based therapy with recurrence >12 months from completion of therapy.
  3. Prior neoadjuvant/adjuvant immune checkpoint inhibitor therapy with recurrence >12 months from completion of therapy.

• Cohort 2: Previously Treated: Participants must have received ≥ 1 prior systemic treatment for locally advanced or metastatic UC. This includes neoadjuvant/adjuvant platinum-based chemotherapy if recurrence occurred within 12 months of completing therapy.

• Cohort 2: Progression or recurrence of UC during or following receipt of most recent therapy.

Key Exclusion Criteria:

• Active keratitis or corneal ulcerations.
• Requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A (CYP3A) or inhibitors of P-glycoprotein (P-gp) including herbal- or food-based inhibitors.
• Any condition requiring current treatment with high dose corticosteroids (> 10 mg daily prednisone or equivalent).
• Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE.
• Has not adequately recovered from recent major surgery (excluding placement of vascular access).
• Receipt of live or attenuated vaccine within 30 days of first dose.
• Cohort 1: Previously Untreated: Prior treatment with a checkpoint inhibitor (CPI) for any other malignancy within the last 12 months.
• Cohort 2: Previously Treated: Received more than 1 prior platinum-based chemotherapy regimen for locally advanced or metastatic UC. This includes neoadjuvant/adjuvant platinum-based chemotherapy if recurrence occurred within 12 months of completing therapy.
• Cohort 2: Prior treatment with enfortumab vedotin or any other MMAE-based therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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956 participants in 6 patient groups

Cohort 1: BT8009 Arm 1

Experimental group

Description:

Participants will receive BT8009 and a standard dose of pembrolizumab.

Treatment:

Drug: BT8009

Drug: BT8009

Drug: Pembrolizumab

Drug: BT8009

Cohort 1: BT8009 Arm 2

Experimental group

Description:

Participants will receive BT8009 and a standard dose of pembrolizumab.

Treatment:

Drug: BT8009

Drug: BT8009

Drug: Pembrolizumab

Drug: BT8009

Cohort 1: Arm 3

Active Comparator group

Description:

Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance

Treatment:

Drug: Gemcitabine + cisplatin Or carboplatin

Drug: Avelumab

Cohort 2: BT8009 Arm 1

Experimental group

Description:

Participants will receive BT8009.

Treatment:

Drug: BT8009

Drug: BT8009

Drug: BT8009

Cohort 2: BT8009 Arm 2

Experimental group

Description:

Participants will receive BT8009.

Treatment:

Drug: BT8009

Drug: BT8009

Drug: BT8009

Cohort 2: Arm 3: BT8009 (Not Recruiting)

Experimental group

Description:

Participants will receive BT8009 and a standard dose of pembrolizumab.

Treatment:

Drug: BT8009

Drug: BT8009

Drug: Pembrolizumab

Drug: BT8009