A Study of Disitamab Vedotin in Previously Treated Solid Tumors That Express HER2

Sponsor

Seagen Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06003231

Collaborator

(none)

190

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This clinical trial is studying advanced or metastatic solid tumors. Once a solid tumor has grown very large in one spot or has spread to other places in the body, it is called advanced or metastatic cancer. Participants in this study must have head and neck squamous cell cancer, non-small cell lung cancer, endometrial cancer, or ovarian cancer. Participants must have tumors that have a marker called HER2.

This clinical trial uses an experimental drug called disitamab vedotin (DV). DV is a type of antibody-drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. In this study, all participants will get DV once every 2 weeks.

This study is being done to see if DV works to treat different types of solid tumors that express HER2. It will also test how safe the drug is for participants. This trial will also study what side effects happen when participants get the drug. A side effect is anything a drug does to your body besides treating the disease.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Squamous Cell of Head and Neck Carcinoma, Non-Small-Cell Lung Ovarian Neoplasms Endometrial Neoplasms	Drug: disitamab vedotin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

190 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Basket Study of Disitamab Vedotin in Adult Subjects With Previously Treated, Locally-Advanced Unresectable or Metastatic Solid Tumors That Express HER2

Anticipated Study Start Date :

Nov 30, 2023

Anticipated Primary Completion Date :

May 31, 2026

Anticipated Study Completion Date :

May 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Disitamab vedotin monotherapy Disitamab vedotin monotherapy	Drug: disitamab vedotin Given into the vein (IV, intravenous) every 2 weeks Other Names: RC48, RC48-ADC

Arm

Intervention/Treatment

Experimental: Disitamab vedotin monotherapy

Disitamab vedotin monotherapy

Drug: disitamab vedotin

Given into the vein (IV, intravenous) every 2 weeks

Other Names:

RC48, RC48-ADC

Outcome Measures

Primary Outcome Measures

Confirmed Objective Response Rate (ORR) per Response Evaluation in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment [Approximately 3 years]
The proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator

Secondary Outcome Measures

Number of participants with adverse events (AEs) [Through 30-37 days after the last dose of DV; approximately 5 years]
Any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention
Number of participants with laboratories abnormalities [Through 30-37 days after the last dose of DV; approximately 5 years]
Number of participants with dose alterations due to AEs [Approximately 5 years]
Confirmed Disease Control Rate (DCR) per RECIST v1.1 by investigator assessment [Approximately 5 years]
The proportion of participants with stable disease (SD) or confirmed CR or PR according to RECIST v1.1
Duration of Response (DOR) per RECIST v1.1 by investigator assessment [Approximately 5 years]
The time from start of the first documentation of objective tumor response of CR or PR (that is subsequently confirmed) to the first documentation of progressive disease (PD) per RECIST v1.1, or to death due to any cause
Duration of Progression Free Survival (PFS) per RECIST v1.1 by investigator assessment [Approximately 5 years]
The time from the start of study treatment to the first documentation of disease progression per RECIST v1.1 or death due to any cause
Overall Survival (OS) [Approximately 5 years]
The time from the start of study treatment to the date of death due to any cause
Pharmacokinetic (PK) parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast) [Approximately 1 month]
Analyzed through cycle 2.
PK parameter - Maximum concentration (Cmax) [Through 30-37 days after the last dose of DV; approximately 5 years]
Analyzed through end of treatment.
PK parameter - Trough concentration (Ctrough) [Through 30-37 days after the last dose of DV; approximately 5 years]
Analyzed through end of treatment.
Incidence of antidrug antibodies (ADAs) [Through 30-37 days after the last dose of DV; approximately 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Cohort 1: HNSCC
Pathologically-documented squamous cell carcinoma of the head and neck with primary tumor site arising from the oral cavity, oropharynx, hypopharynx, and larynx
Unresectable locally recurrent or metastatic stage disease
Prior therapies:
Participants must have disease progression after treatment with a platinum-based therapy
No more than 1 line of cytotoxic chemotherapy for advanced disease
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
No more than 2 prior lines of cytotoxic chemotherapy for advanced disease
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
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
HER2 expression of 1+, 2+, or 3+, as determined by local IHC testing on a fresh or archival tumor tissue
Measurable disease per RECIST v1.1 criteria as assessed by the investigator
Able to provide formalin-fixed, paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides)
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

Exclusion Criteria:

Prior treatment with an MMAE-containing agent.
Previous treatment with HER2-directed ADCs
Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin.
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.
Active untreated CNS or leptomeningeal metastasis