A Study of Disitamab Vedotin in Previously Treated Solid Tumors That Express 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

19 Sep 2024 → ongoing

Decision date (initial)

2024-06-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-504445-31-00

ClinicalTrials.gov

NCT06003231

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic, Efficacy, Therapy

To evaluate the antitumor activity of disitamab vedotin in participants with previously treated, locally-advanced unresectable or metastatic (LA/m) HER2 expressing solid tumors

Secondary objectives 4

1. To evaluate the safety and tolerability profile of disitamab vedotin
2. To assess antitumor activity of disitamab vedotin per investigator assessment by other clinically relevant measures
3. To evaluate the pharmacokinetics (PK) of disitamab vedotin
4. To evaluate the immunogenicity of disitamab vedotin

Conditions and MedDRA coding

Carcinoma, Head and Neck

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Cohort 1: HNC •Must have pathologically-documented carcinoma of the head and neck with primary tumor site arising from the oral cavity, salivary gland, oropharynx, hypopharynx, and larynx; tumors arising from the nasopharynx are excluded. •Unresectable locally recurrent or metastatic stage disease •Prior therapies: -Participants must have disease progression after treatment with a platinum-based therapy or other first line treatment regimen
2. Cohort 2: NSCLC •Pathologically documented NSCLC •Unresectable locally-advanced or metastatic stage disease •Prior therapies: -Must have progressed during or after a platinum-based therapy or, within 6 months of platinum-based adjuvant, neoadjuvant, or concomitant chemoradiotherapy for early or locally-advanced stage disease -Must have received prior anti-PD(L)1 therapy, unless contraindicated - Participants with known AGAs must have received appropriate targeted therapy, where available -No more than 2 prior lines of cytotoxic chemotherapy for advanced disease
3. Cohort 3: Ovarian Cancer •Pathologically documented epithelial cancers of ovarian, fallopian tube, or peritoneal origin •Unresectable locally-advanced or metastatic stage disease •Prior therapies -Must have platinum resistant disease (6 months or less between the completion of platinum-based treatment and identification of recurrence) -Must not have received more than 4 lines of prior cytotoxic chemotherapies for advanced disease -May have received prior anti-PD(L)1 therapy
4. Cohort 4: Endometrial Cancer •Must have pathologically documented adenocarcinoma of the endometrium •Must have unresectable locally-advanced or metastatic stage disease. •Prior therapies: -Must have relapsed/progressed after at least one prior platinum-based chemotherapy for recurrent, metastatic or primary unresectable disease -Must not have received more than 3 lines of prior cytotoxic chemotherapies for advanced disease -May have received prior anti-PD(L)1 therapy
5. HER2 expression of 1+, 2+, or 3+, as determined by local IHC testing on a fresh or archival tumor tissue. Note: Subjects with HER2 mutations are eligible.
6. Measurable disease per RECIST v1.1 criteria as assessed by the investigator.
7. Able to provide formalin-fixed, paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides).
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Exclusion criteria 4

1. Prior treatment with an MMAE-containing agent
2. Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin
3. History of another invasive malignancy within 2 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy
4. Active untreated CNS or leptomeningeal metastasis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by the investigator.

Secondary endpoints 9

1. Type, incidence, severity, seriousness, and relatedness of adverse events (AEs) including AEs of special interest (AESIs).
2. Type, incidence, and severity of laboratory abnormalities as well as significant changes from baseline
3. Frequency of treatment interruptions, dose reductions and treatment discontinuations due to AEs.
4. Confirmed disease control rate (DCR) per RECIST v1.1 as assessed by the investigator
5. Duration of response (DOR) per RECIST v1.1 as assessed by the investigator
6. Progression free survival (PFS) per RECIST v1.1 as assessed by the investigator
7. Overall survival (OS)
8. Select PK parameters of disitamab vedotin, total antibody (TAb) and unconjugated MMAE
9. Incidence of antidrug antibodies (ADA) 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

Irina Stratila

Third parties 16

Locations

4 EU/EEA countries · 18 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 28 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