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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

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 have progressed following 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: Patients with 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 have progressed following prior therapy.

- * Cohort B-5: Patients with triple-negative breast cancer 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 progressed following prior therapy.

- * Cohort B-6: Patients with 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 have progressed following 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, ovarian, triple negative breast, or non-small cell lung cancer that have been previously treated with a locally approved therapy.
Key Exclusion Criteria (all patients):
* Clinically relevant troponin elevation

- * Uncontrolled diabetes

- * Known active or untreated CNS and/or carcinomatous meningitis

- * Grade ≥2 peripheral neuropathy

- * Active keratitis or corneal ulcerations

- * 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: Bicycle Tx Limited

Phone: 617-945-8155

Email: clinicalstudies@bicycletx.com

LOCATION