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

Study Overview
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Brief Summary
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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.

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

Conditions
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Carcinoma, Squamous Cell of Head and Neck, Carcinoma, Non-Small-Cell Lung, Ovarian Neoplasms, Endometrial Neoplasms

Intervention / Treatment
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* Drug: disitamab vedotin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Disitamab vedotin monotherapy<br>Disitamab vedotin monotherapy | Drug: disitamab vedotin<br>* Given into the vein (IV, intravenous) every 2 weeks<br>* Other names: RC48, RC48-ADC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Objective Response Rate (ORR) per Response Evaluation in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment | 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 | Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | 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 | Through 30-37 days after the last dose of DV; approximately 5 years | 
| 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 | The proportion of participants with stable disease (SD) or confirmed CR or PR according to RECIST v1.1 | Approximately 5 years | 
| Duration of Response (DOR) per RECIST v1.1 by investigator assessment | 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 | Approximately 5 years | 
| Duration of Progression Free Survival (PFS) per RECIST v1.1 by investigator assessment | 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 | Approximately 5 years | 
| Overall Survival (OS) | The time from the start of study treatment to the date of death due to any cause | Approximately 5 years | 
| Pharmacokinetic (PK) parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast) | Analyzed through cycle 2. | Approximately 1 month | 
| PK parameter - Maximum concentration (Cmax) | Analyzed through end of treatment. | Through 30-37 days after the last dose of DV; approximately 5 years | 
| PK parameter - Trough concentration (Ctrough) | Analyzed through end of treatment. | Through 30-37 days after the last dose of DV; approximately 5 years | 
| Incidence of antidrug antibodies (ADAs) |  | Through 30-37 days after the last dose of DV; approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HNSCC, NSCLC, Ovarian Cancer, Endometrial Cancer