A Study of Disitamab Vedotin Alone and with Pembrolizumab in Urothelial Cancer That Expresses HER2

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Seagen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2022-12-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Seagen Inc.

External identifiers

EU CT number

2022-500030-28-00

ClinicalTrials.gov

NCT04879329

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacokinetic

To evaluate the efficacy as measured by cORR assessed by BICR for disitamab vedotin monotherapy in previously treated subjects with LA/mUC that expresses HER2 (HER2-positive [IHC 3+, or IHC 2+ and ISH-positive], and HER2-low [IHC 2+ and ISH-negative, or IHC 1+])

To evaluate the efficacy as measured by cORR assessed by BICR for disitamab vedotin alone and combined with pembrolizumab in treatment-naive subjects with LA/mUC that expresses HER2

Secondary objectives 10

1. To evaluate the efficacy as measured by cORR assessed by investigator for disitamab vedotin monotherapy in treatment naive subjects and in previously treated subjects with LA/mUC that expresses HER2, and for disitamab vedotin combined with pembrolizumab in treatment-naïve subjects with LA/mUC that expresses HER2
2. To evaluate the efficacy as measured by DOR for disitamab vedotin monotherapy in treatment naive subjects and in previously treated subjects with LA/mUC that expresses HER2, and for disitamab vedotin combined with pembrolizumab in treatment-naive subjects with LA/mUC that expresses HER2
3. To evaluate the efficacy as measured by PFS for disitamab vedotin monotherapy in treatment naive subjects and in previously treated subjects with LA/mUC that expresses HER2, and for disitamab vedotin combined with pembrolizumab in treatment-naive subjects with LA/mUC that expresses HER2
4. To evaluate the efficacy as measured by DCR for disitamab vedotin monotherapy in treatment naive subjects and in previously treated subjects with LA/mUC that expresses HER2, and for disitamab vedotin combined with pembrolizumab in treatment-naive subjects with LA/mUC that expresses HER2
5. To evaluate the efficacy as measured by OS for disitamab vedotin monotherapy in treatment naive subjects and in previously treated subjects with LA/mUC that expresses HER2, and for disitamab vedotin combined with pembrolizumab in treatment-naive subjects with LA/mUC that expresses HER2
6. To evaluate the safety and tolerability of disitamab vedotin monotherapy and the combination of disitamab vedotin and pembrolizumab in treatment-naive subjects (monotherapy and combination) and previously treated subjects with LA/mUC that expresses HER2 (monotherapy)
7. To investigate the PK characteristics of disitamab vedotin, free MMAE, and TAb when administered alone and in combination with pembrolizumab
8. To investigate the PK characteristics of pembrolizumab when administered in combination with disitamab vedotin
9. To evaluate the immunogenicity of disitamab vedotin when administered alone and in combination with pembrolizumab
10. To evaluate the immunogenicity of pembrolizumab when administered in combination with disitamab vedotin

Conditions and MedDRA coding

Urothelial carcinoma

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Expected survival ≥12 weeks
2. Histologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
3. Cohorts A and B: Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy Neoadjuvant or adjuvant systemic therapy, with progression within 12 months of completing last dose of therapy, is considered a line of prior therapy. Maintenance avelumab therapy delivered following first-line platinum therapy is not considered a separate line of therapy. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second-line treatment is allowed
4. Cohort C: No prior systemic therapy for LA/mUC Neoadjuvant or adjuvant therapy, including PD-(L1) inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy
5. Cohorts A and B only: Radiographically documented disease progression during or after the most recent line of therapy for LA/mUC
6. At least one measurable lesion by investigator assessment based on RECIST version 1.1.
7. Cohort C only: Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation
8. Participants must be able to provide archived tumor tissue prior to treatment initiation. If archival tissue is not available, a baseline biopsy is required within 28 days of Cycle 1 Day 1.
9. HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
10. Eastern Cooperative Oncology Group (ECOG) performance status score: Cohorts A and B: ECOG of 0 or 1 Cohort C: ECOG of 0, 1, or 2

Exclusion criteria 8

1. Known hypersensitivity to disitamab vedotin, pembrolizumab (in Cohort C), or any of their components
2. Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study
3. Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
4. Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy
5. Major surgery that has not fully recovered within 4 weeks prior to dose administration
6. Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline
7. Other malignant tumors within 3 years of study treatment, except for: Prostate cancer treated with definitive intent (surgically or with radiation therapy) ≥ 1 year prior to treatment initiation is acceptable Malignancies that can be cured after treatment
8. There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. cORR (confirmed CR and confirmed PR) per RECIST v1.1 as assessed by BICR
2. cORR per RECIST v1.1 as assessed by BICR

Secondary endpoints 10

1. cORR per RECIST v1.1, as assessed by the investigator
2. Confirmed DOR per RECIST v1.1, as assessed by BICR ● Confirmed DOR per RECIST v1.1, as assessed by the investigator
3. PFS per RECIST v1.1, as assessed by BICR ● PFS per RECIST v1.1, as assessed by the investigator
4. DCR (confirmed CR, confirmed PR, and stable disease) per RECIST v1.1, as assessed by BICR ● DCR per RECIST v1.1, as assessed by the investigator
5. OS
6. Type, incidence, relatedness, severity and seriousness of AEs ● Treatment discontinuations, dose reductions, or dose delays due to AEs ● Type, incidence and severity of laboratory abnormalities ● ECG abnormalities, including changes in QTc ● Effect on LVEF
7. PK parameters of disitamab vedotin, free MMAE, and TAb
8. PK parameters of pembrolizumab
9. Incidence of ADA against disitamab vedotin
10. Incidence of ADA to pembrolizumab

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Seagen Inc.

Sponsor organisation

Seagen Inc.

Address

21823 30th Drive Southeast

City

Bothell

Postcode

98021-3907

Country

United States

Scientific contact point

Organisation

Seagen Inc.

Contact name

Kevin Sokolowski

Public contact point

Organisation

Seagen Inc.

Contact name

Seagen Clinical Trial Information

Locations

4 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications