Carcinoma, Non-Small-Cell Lung, Endometrial Neoplasms, Head and Neck Neoplasms, Ovarian Neoplasms
Conditions
Keywords
NSCLC, Ovarian Cancer, Endometrial Cancer, Head and Neck Cancer
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 cancer, non-small cell lung cancer, endometrial cancer, or ovarian cancer. In the first part of the study, 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.
Interventions
DRUGdisitamab vedotin
Given into the vein (IV, intravenous) every 2 weeks
Sponsors
Seagen, a wholly owned subsidiary of Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cohort 1: Head and neck cancer (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 * Cohort 2: Non-small cell lung cancer (NSCLC) * Pathologically documented NSCLC * Unresectable locally-advanced or metastatic stage disease * Prior therapies * Must have progressed during or after a platinum-based therapy for LA/metastatic disease 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 * 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 * Participants with known BRCA mutations are permitted, but participants must have received targeted therapy with a PARP inhibitor * 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. Note: Participants with HER2 mutations are eligible. * 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. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Progression free survival (PFS) per RECIST v1.1 by investigator assessment | Approximately 5 years | PFS is defined as the time from the start of study treatment to the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurs first |
| 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 | — |
Countries
Australia, Canada, Italy, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed