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

Study Identifier:
BT8009-100
CT.gov Identifier:
NCT04561362
EudraCT Identifier:
2020-002719-23
EU Trial (CTIS) Number:
2023-509781-37-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

To evaluate BT8009 in patients with advanced solid tumors.

To evaluate Safety, Pharmacokinetics, and Preliminary Clinical Activity of 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.

To evaluate safety and tolerability of chosen RP2D of BT8009 in patients with renal insufficiency.

To evaluate safety and tolerability of weekly and every other week BT8009 administration, alone and in combination with q4w nivolumab.

Determination of both a realistic phase 2 dose and a sequence will also be key to further exploration of safety and efficacy signals, along with an early examination of the role of baseline mmunohistochemistry-ascertained levels of tumor Nectin-4.

Radiologic tumor assessments for response per RECIST will be taken every two months.

To assess the impact of renal impairment on the PK of BT8009 and MMAE

Patients were grouped by renal functions based on creatinine clearance at C1D1 and exposures (AUC0-inf [ng*h/mL] and Cmax [ng/mL]) from C1D1 for BT8009 and MMAE were generated using non-compartmental analyses and dose-normalized.

To evaluate BT8009 ± pembrolizumab in pts with advanced solid tumors associated with Nectin-4 expression.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Bladder
  • Breast Cancers
  • Gene Mutations
  • Biomarkers
  • Non-Small Cell Lung Cancer
  • Ovarian
  • Solid Tumor
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Part A-1 -BT8009 Monotherapy Dose Escalation
    • Read More
  • Drug: Experimental: Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation
  • Drug: Drug: Pembrolizumab
  • Drug: Other Names:
  • Drug: Experimental: Cohort B-2- BT8009 Monotherapy Dose Expansion
  • Drug: Experimental: Cohort B-3- BT8009 Monotherapy Dose Expansion
  • Drug: Experimental: Cohort B-4- BT8009 Monotherapy Dose Expansion
  • Drug: Experimental: Cohort B-5- BT8009 Monotherapy Dose Expansion
  • Drug: Experimental: Cohort B-6- BT8009 Monotherapy Dose Expansion
  • Drug: Experimental: Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion
  • Drug: Experimental: Part D - BT8009 Monotherapy Supplementary PK
  • Drug: Experimental: Part B-8 - BT8009 Monotherapy Dose Expansion
  • Drug: Experimental: Part B-9 - BT8009 Monotherapy Dose Expansion
  • Drug: BT8009 monotherapy was administered weekly (2.5, 5, 7.5 mg/m2) or every other week (7.5, 10 mg/m2) of a 28-day cycle, or on days 1 and 8 of a 21-day cycle (7.5 mg/m2).
  • Drug: Patients will receiving BT8009 monotherapy. Intravenous doses were administered ranging from 2.5-10 mg/m2 (weekly, bi-weekly, or on Days 1 and 8 of a 21-day cycle) . Intensive PK sampling was collected following C1D1 dosing.
  • Drug: ASCO 2024:
  • Drug: All pts who received the RP2D of 5 mg/m2 BT8009 monotherapy QW across dose escalation and expansion phases were included for analysis.
  • Drug: ASCO 2025
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    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 B-8: Locally advanced (unresectable) or metastatic, histologically confirmed breast cancer, either TNBC or hormone receptor (HR) positive and HER-2 negative according to ASCO/CAP guidelines and up to 3 prior lines of therapy for advanced (unresectable) or metastatic disease. Cohort B-9: Histologically confirmed advanced/metastatic squamous or non-squamous NSCLC, negative for oncogenic driver mutations (EGFR, KRAS, ALK, BRAF, MET, ERRB2). 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. Part D supplementary PK: Patients must have histologically confirmed urothelial (transitional cell) carcinoma (patients with squamous differentiation or mixed cell types are eligible); ovarian; triple-negative breast; or non-small cell lung cancer that have been previously treated with a locally approved therapy.
    Exclusion criteria
    • 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
    • Parts B-8 and B-9: Prior treatment with an ADC containing an MMAE (vedotin) payload.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Bernard Doger de Speville
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Bladder
    Breast Cancers
    Gene Mutations
    Biomarkers
    Non-Small Cell Lung Cancer
    Ovarian
    Solid Tumor