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Phase I Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Japanese Patients with Advanced Malignancies associated with Nectin-4 Expression

Phase I Study of BT8009 in Japanese Patients with Advanced Malignancies associated with Nectin-4 Expression

Leslie DeMars

BicycleTx Limited

Blocks A & B, Portway Building, Granta Park, Great Abington, Cambridge CB21 6GS, United Kingdom

clinicalstudies@bicycletx.com

Hara Yo

CMIC Co.,Ltd.

1-1-1, Shibaura, Minato-ku, Tokyo 105-0023 Japan

+81-80-9552-5257

ClinicalTrialInformation@cmic.co.jp

Not Recruiting

Aug. 14, 2024

Interventional

non-randomized controlled trial

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Eastern Cooperative Oncology Group (ECOG) of 0 or 1
2. Measurable disease as defined by RECIST v1.1
3. Life expectancy >-12 weeks after the start of BT8009 treatment.
4. Must have exhausted all standard treatment options, including appropriate targeted therapies; patients for which no standard therapy is considered appropriate or to provide clinical benefit, as assessed by the Investigator. Patient must have recurred after or been refractory to most recent prior therapy.
5. Patients with advanced, histologically confirmed the following solid tumor:
a. urothelial (transitional cell) carcinoma; or
b. pancreatic, breast, NSCLC, gastric, esophageal, head and neck, or ovarian tumors

1. Current treatment with strong inhibitors or strong inducers of CYP3A or inhibitors of P- gp including herbal- or food-based.
2. Known hypersensitivity to any of the ingredients of the investigational product(s), including MMAE.
3. Active keratitis or corneal ulcerations.
4. Grade >-2 peripheral neuropathy.
5. Uncontrolled diabetes, defined as hemoglobin A1C (HbA1c) >-8%
6. Patients who are pregnant (including those who have been determined to be possibly pregnant based on e.g. a physician's interview) and/or lactating (not allowed to be enrolled even after discontinuation of breastfeeding)
7. Patients with uncontrolled hypertension (systolic blood pressure [BP] Systolic BP >-140 mm Hg or diastolic BP >-90 mm Hg) prior to first dose of BT8009
8. Prior Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN) on any MMAE-conjugated drug
9. Active interstitial lung disease or pneumonitis, or a history of interstitial lung disease or pneumonitis requiring treatment with steroids or other immunosuppressive medications

Exclusion Criteria Specific to Part B: Combination with pembrolizumab
10. Prior intolerance or known hypersensitivity to immune checkpoint inhibitor
11. Prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonist or CTLA-4 inhibitors
a. Prior treatment with a PD-1, PD-L1 or PD-L2 inhibitor is permitted

Both

Advanced solid tumor malignancies

In Part A, (BT8009 monotherapy) participants will receive either 5 mg/m2 (Arm 1) once weekly (i.e., on Days 1, 8, and 15,) or 6 mg/m2 (Arm 2) on Days 1 and 8 of a 21-day cycle.
In Part B (BT8009 + Pembrolizumab) participants will receive either 5 mg/m2 (Arm 1) once weekly (i.e., on Days 1, 8, and 15,) or 6 mg/m2 (Arm 2) on Days 1 and 8 of a 21-day cycle and pembrolizumab every 3 weeks on Day 1.
Treatment duration is until radiographic progression, intolerability, or other reasons for withdrawal occurs. Patients may receive pembrolizumab for up to 2 years.

- Adverse Events as characterized by type, frequency, severity (as graded by CTCAE version 5.0), seriousness, and relationship to BT8009 and/or pembrolizumab.
- Laboratory abnormalities as characterized by type, frequency, severity (as graded by CTCAE version 5.0).
- Number of drug-related Adverse Events during safety evaluation period.
- PK parameters of BT8009 and MMAE as monotherapy and in combination with pembrolizumab, such as maximum concentration (Cmax), area under the curve (AUC), and half-life (t1/2).

+81-3-3542-2511

July. 24, 2024

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