A Study of Disitamab Vedotin Alone or 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]

Trial duration

10 Jun 2024 → ongoing

Decision date (initial)

2024-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Seagen Inc.

External identifiers

EU CT number

2022-500030-28-01

ClinicalTrials.gov

NCT04879329

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Safety, Efficacy

To evaluate the efficacy as measured by cORR assessed by BICR for disitamab vedotin monotherapy in previously treated participants 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 participants with LA/mUC that expresses HER2

Secondary objectives 8

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

Conditions and MedDRA coding

Urothelial carcinoma

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical trials/trial data and results/data requests. URL: https://www.pfizer.com/science/clinical trials/trial data and results/data requests

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Expected survival ≥12 weeks
2. Locally-advanced unresectable or metastatic (American Joint Commission on Cancer Stages TNM Stage IIIB–IV [Amin 2017]) UC with histopathological confirmation, including UC originating from the renal pelvis, ureters, bladder, or urethra. Mixed-cell type tumors are eligible as long as urothelial (transitional cell) carcinoma is the predominant cell type.
3. Prior therapy: a.Participantsmust have received only 1 or 2 lines of prior systemic therapy for LA/mUC, including 1 line of platinum-containing chemotherapy. i.Neoadjuvant or adjuvant systemic therapy, with progression within 12 months of completing final dose of therapy, is considered as one line of prior therapy. ii.Maintenance avelumab therapy delivered following first-line platinum therapy is not considered a separate line of therapy. iii.Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second-line treatment is allowed.
4. Radiographically documented disease progression during or after the most recent line of therapy for LA/mUC
5. At least one measurable lesion by investigator assessment based on RECIST version 1.1.
6. Participants must be willing and able to provide archived (formalin-fixed paraffin-embedded tumor tissue blocks (or alternatively freshly sectioned slides; see laboratory manual for details and Section 7.1.3). This must be obtained prior to study treatment initiation and will be sent to a sponsor-designated central laboratory for biomarker analysis. If archival tissue is not available, then a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days prior to the Cycle 1 Day 1. Biopsy must provide adequate tissue for HER2 testing.
7. HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the provided tumor tissue sample of muscle-invasive or metastatic UC.
8. Participants must have an ECOG performance status of 0 or 1.

Exclusion criteria 9

1. Known hypersensitivity to disitamab vedotin or any of their components
2. Received antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) or participated in another clinical study within 2 weeks prior to the start of the study (defined as Cycle 1 Day 1 for Cohorts A and B)
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. Received live or live-attenuated vaccines within 4 weeks prior to study treatment initiation or plan on receiving such vaccines during the course of study treatment
8. Participants with acute, chronic or symptomatic infections, including: A. Ongoing symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. B. History of human immunodeficiency virus infection. C. History of hepatitis B virus (HBV) infection (defined as positive for HBV surface antigen) or known active hepatitis C virus (HCV) infection (defined as HCV RNA [qualitative] is detected).
9. Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interpretation of outcomes, including active opportunistic infections or advanced (severe) infections, or uncontrolled diabetes.

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 8

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. Incidence of ADA and NABs against disitamab vedotin

Investigational products

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

Test 1

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

Seagen Trial Information Support

Public contact point

Organisation

Seagen Inc.

Contact name

Seagen Trial Information Support

Third parties 17

Locations

4 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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