Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06157892




Registration number
NCT06157892
Ethics application status
Date submitted
27/11/2023
Date registered
6/12/2023
Date last updated
20/11/2024

Titles & IDs
Public title
A Study of Disitamab Vedotin Alone or With Other Anticancer Drugs in Solid Tumors
Scientific title
A Phase 1b/2 Open-Label Study of Disitamab Vedotin Monotherapy or in Combination With Other Anticancer Therapies in Solid Tumors
Secondary ID [1] 0 0
SGNDV-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Neoplasms 0 0
Gastroesophageal Junction Adenocarcinoma 0 0
HER2 Low Breast Neoplasms 0 0
HER2 Positive Breast Neoplasms 0 0
Stomach Neoplasms 0 0
Triple Negative Breast Neoplasms 0 0
Metastatic Breast Cancer 0 0
Metastatic Gastric Cancer 0 0
Advanced Breast Cancer 0 0
Advanced Gastric Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - disitamab vedotin
Treatment: Drugs - tucatinib

Experimental: Dose Escalation - Previously treated advanced GC/GEJC or breast cancer - disitamab vedotin + tucatinib

Experimental: Cohort A monotherapy - HER2-low 2L or 3L breast cancer - disitamab vedotin monotherapy

Experimental: Cohort A - HER2-low 2L or 3L breast cancer - disitamab vedotin + tucatinib

Experimental: Cohort B monotherapy - HER2+ 3L or higher breast cancer - disitamab vedotin monotherapy

Experimental: Cohort B - HER2+ 3L or higher breast cancer - disitamab vedotin + tucatinib

Experimental: Cohort C monotherapy - HER2-low 2L GC/GEJC - disitamab vedotin monotherapy

Experimental: Cohort C - HER2-low 2L GC/GEJC - disitamab vedotin + tucatinib


Treatment: Drugs: disitamab vedotin
Given into the vein (IV; intravenous)

Treatment: Drugs: tucatinib
300mg given twice daily by mouth (orally)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with dose limiting toxicities DLTs) in dose escalation phase
Timepoint [1] 0 0
Up to 28 days
Primary outcome [2] 0 0
Number of participants with adverse events (AEs)
Timepoint [2] 0 0
Through 30 days after the last study treatment; approximately 5 years
Primary outcome [3] 0 0
Number of participants with laboratory abnormalities
Timepoint [3] 0 0
Through 30-37 days after the last study treatment: approximately 5 years
Primary outcome [4] 0 0
Number of participants with dose alterations
Timepoint [4] 0 0
Through 30-37 days after the last study treatment: approximately 5 years
Primary outcome [5] 0 0
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment
Timepoint [5] 0 0
Approximately 3 years
Secondary outcome [1] 0 0
Duration of response (DOR) per RECIST v1.1 by investigator assessment
Timepoint [1] 0 0
Approximately 5 years
Secondary outcome [2] 0 0
Disease control rate (DCR) per RECIST v1.1 by investigator assessment
Timepoint [2] 0 0
Approximately 5 years
Secondary outcome [3] 0 0
Progression free survival (PFS) per RECIST v1.1 by investigator assessment
Timepoint [3] 0 0
Approximately 5 years
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
Approximately 5 years
Secondary outcome [5] 0 0
Pharmacokinetic (PK) parameter - Maximum concentration (Cmax)
Timepoint [5] 0 0
Through 30-37 days after the last study treatment; approximately 5 years
Secondary outcome [6] 0 0
PK parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast)
Timepoint [6] 0 0
Approximately 1 month
Secondary outcome [7] 0 0
Incidence of anti-drug antibodies (ADAs) against disitamab vedotin
Timepoint [7] 0 0
Through 30-37 days after the last study treatment; approximately 5 years

Eligibility
Key inclusion criteria
General Inclusion Criteria

* Measurable disease according to RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

Dose Escalation Phase Inclusion Criteria

* Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
* Locally-advanced, unresectable, or metastatic stage
* HER2 status IHC 1+ or higher by most recent local assessment.
* Must have experienced disease progression on or after standard of care therapies or be intolerant of standard of care therapies.

Cohort A (HER2-Low Breast Cancer) Inclusion Criteria

* Histologically or cytologically confirmed diagnosis of breast carcinoma
* Locally-advanced, unresectable, or metastatic stage
* HER2-low status determined by most recent local assessment (IHC 1+ or IHC 2+/ISH-negative)
* Prior therapies requirements

* No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC.
* Participants with known BRCA mutation must have received a PARP-inhibitor where available and not medically contraindicated
* Have progression on or after, or intolerant to, T-DXd, sacituzumab govitecan, or other topoisomerase I inhibitor therapies, if available as local standard of care therapy
* Participants with HR+ tumors must have endocrine therapy refractory disease:

* Progressed on =2 lines of endocrine therapy for LA/mBC AND had received a CDK4/6 inhibitor in the adjuvant or metastatic setting OR
* Progressed on 1 line of endocrine therapy for LA/mBC AND had a relapse while on adjuvant endocrine therapy after definitive surgery for primary tumor AND had received a CDK4/6 inhibitor in the adjuvant or advanced setting
* Participants with HR negative, HER2-low and PD-L1-positive (CPS 10 or greater) tumors must have received pembrolizumab with chemotherapy if available as local standard of care therapy.

Cohort B (HER2+ Breast Cancer) Inclusion Criteria

* Histologically or cytologically confirmed diagnosis breast carcinoma
* Locally-advanced, unresectable, or metastatic stage
* HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+)
* Participants must have:

* Received prior trastuzumab, pertuzumab and a taxane if available as local standard of care therapy.
* Have progression on or after, or intolerant to, T-DXd or other topoisomerase I inhibitor therapies
* No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC

Cohort C (HER2-Low Gastric or Gastroesophageal Junction Adenocarcinoma) Inclusion Criteria

* Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
* Locally-advanced, unresectable, or metastatic stage
* HER2-low expression defined as IHC 1+ or IHC 2+/ISH-negative determined by most recent local assessment
* Willing and able to provide archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks
* Participants must have received:

* Prior systemic therapy with platinum, fluorouracil, or taxane for locally advanced unresectable or metastatic disease
* Progression within 6 months of last dose of (neo)adjuvant cytotoxic chemotherapy is considered as 1 line of systemic therapy for LA/mGC/GEJC
* Prior anti-PD-(L)1 therapy is allowed
* No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADC) for LA/mGC/GEJC
* Must not have received prior treatment with HER2 directed therapy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin or tucatinib
* Prior therapy with ADCs with MMAE payload
* Prior therapy with tucatinib
* Active CNS and/or leptomeningeal metastasis.
* Participants who have received prior systemic anticancer treatment including investigational agents within 4 weeks prior to first dose of study treatment
* History of other invasive malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
* Unable to swallow oral tablets or capsules or any significant GI disease which would preclude the adequate oral absorption of medications

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/05/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2030
Actual
Sample size
Target
198
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Othe
Recruitment hospital [1] 0 0
Peninsula and South East Oncology - Frankston
Recruitment postcode(s) [1] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nevada
Country [9] 0 0
United States of America
State/province [9] 0 0
New Mexico
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Wisconsin
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Italy
State/province [17] 0 0
Other
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Other
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seoul
Country [20] 0 0
Spain
State/province [20] 0 0
Other
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Other

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Seagen Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
RemeGen Co., Ltd.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This clinical trial is studying solid tumor cancers. A solid tumor is one that starts in part of your body like your lungs or liver instead of your blood. Once they've grown bigger in one spot or spread to other parts of the body, they're harder to treat. This is called advanced or metastatic cancer.

Participants in this study must have breast cancer or gastric cancer. Participants must have tumors that have HER2 on them. This allows the cancer to grow more quickly or spread faster. There are few treatment options for patients with advanced or metastatic solid tumors that express HER2.

This clinical trial uses an experimental drug called disitamab vedotin (DV). Disitamab vedotin is a type of antibody drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them.

This clinical trial uses a drug called tucatinib, which has been approved to treat cancer in the United States and some other countries. This drug is sold under the brand name TUKYSA®.

This study will test how safe and how well DV, with or without tucatinib, is for participants with solid tumors. This study will also test what side effects happen when participants take these drugs. A side effect is anything a drug does to the body besides treating the disease.
Trial website
https://clinicaltrials.gov/study/NCT06157892
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Seagen Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Seagen Trial Information Support
Address 0 0
Country 0 0
Phone 0 0
866-333-7436
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06157892