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Treatment for advanced cancers expressing Nectin-4

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

Phase1; Phase2 Interventional BicycleTx Limited · NCT04561362

This study is testing a new treatment called BT8009, alone and with another drug, to see if it can help people with advanced cancers that have a specific marker called Nectin-4.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment329 (estimated)
Ages18 Years and up
SexAll
SponsorBicycleTx Limited Industry-sponsored
Drugs / interventionsenfortumab, Pembrolizumab
Locations29 sites (Denver, Colorado and 28 other locations)
Trial IDNCT04561362 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of BT8009, both alone and in combination with pembrolizumab, in patients with advanced solid tumors that express Nectin-4. It is a Phase I/II, multicenter, open-label trial that includes a dose-escalation phase to determine the optimal dosing schedule and a dose expansion phase to assess clinical activity. Participants will be monitored for dose-limiting toxicities, overall response rates, safety, and pharmacokinetics. The study aims to provide new treatment options for patients who have exhausted standard therapies.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced solid tumors expressing Nectin-4 who have exhausted all standard treatment options.

Not a fit: Patients with early-stage cancers or those who have not yet received standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with advanced malignancies that express Nectin-4.

How similar studies have performed: Other studies targeting Nectin-4 have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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 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.

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
* Parts B-8 and B-9: Prior treatment with an ADC containing an MMAE (vedotin) payload.

Where this trial is running

Denver, Colorado and 28 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Urinary Bladder NeoplasmTriple Negative Breast NeoplasmsHormone Receptor Positive, HER2-negative NeoplasmsHormone Receptor Positive, HER2-low NeoplasmsBreast NeoplasmsNon-Small-Cell Lung NeoplasmsOvarian NeoplasmAdvanced Solid Tumor
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.