A Study of Felmetatug Vedotin/SGN-B7H4V in Advanced Solid Tumors
- Conditions
- Ovarian NeoplasmsPeritoneal NeoplasmsFallopian Tube NeoplasmsTriple Negative Breast NeoplasmsHER2 Negative Breast NeoplasmsHormone Receptor Positive Breast NeoplasmsEndometrial NeoplasmsCarcinoma, Non-Small-Cell LungCholangiocarcinomaGallbladder Carcinoma
- Interventions
- Registration Number
- NCT05194072
- Lead Sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Brief Summary
The purpose of the study is to test the safety of the medicine called Felmetatug Vedotin alone and with pembrolizumab in participants with solid tumors. It will also look at the side effects of this medicine. A side effect is anything a medicine does to the body besides treating the disease.
This study is seeking for participants who either have cancer:
* that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable),
* has spread through the body (metastatic), or have some cancer left over after surgery.
This study will have five parts.
* Parts A and B of the study will find out how much Felmetatug Vedotin should be given to participants.
* Part C will use the amount found in Parts A and B to find out how safe Felmetatug Vedotin is and if it works to treat solid tumor cancers.
* Part D will find out if and how much Felmetatug Vedotin can be given with pembrolizumab.
* Part E will use the amount found in Part D to find out how safe Felmetatug Vedotin with pembrolizumab is and if it works to treat triple negative breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 236
For Parts A, B, and C:
-
Participants must have one of the following histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumor types:
- High-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
- HER2-negative, HR positive breast cancer
- Triple-negative breast cancer (TNBC)
- Endometrial carcinoma
- Non-small cell lung cancer (Squamous cell carcinoma [SqCC], Adenocarcinoma [AC])
- Cholangiocarcinoma or gallbladder carcinoma
- Adenoid cystic carcinoma (ACC) For Part D: Participants must have histologically or cytologically confirmed locally advanced unresectable or metastatic TNBC.
For Part E:
-
Cohort E1: Participants must have histologically or cytologically confirmed locally advanced unresectable or metastatic TNBC and must have CPS≥10 by local testing
-
Cohort E2: Participants must have histologically or cytologically confirmed locally advanced unresectable or metastatic TNBC and must have CPS<10 by local testing
-
Cohort E3: Participants must have triple negative breast cancer with residual disease following neoadjuvant therapy and definitive surgery
- Parts A and B: Participants must have disease that is relapsed or refractory or be intolerant to SOC therapies, and, in the judgement of the investigator, should have no appropriate SOC therapeutic option
- Part C: Participants must have disease that is relapsed or refractory or be intolerant to SOC therapies.
- Part D and E1/E2: Participants must have had no prior treatment for locally advanced unresectable or metastatic TNBC
- Part E3: Participants must have completed at least 6 cycles of neoadjuvant therapy for locally advanced unresectable or metastatic TNBC
- Tumor tissue is required for enrollment.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Measurable disease per RECIST version 1.1 at baseline (not applicable for E3 participants).
-
History of another malignancy within 3 years before the first dose of study drug. Any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
-
Known active central nervous system metastases. Participants with previously treated brain metastases may participate provided they:
- are clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment
- have no new or enlarging brain metastases
- and are off corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to the first dose of study treatment.
-
Carcinomatous meningitis
-
Previous receipt of an MMAE-containing agent or an agent targeting B7-H4
-
Pre-existing neuropathy ≥ Grade 2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
-
Corneal disease or injury requiring treatment or active monitoring
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Felmetatug Vedotin (Parts A, B, and C) Felmetatug Vedotin Felmetatug Vedotin monotherapy Felmetatug Vedotin and Pembrolizumab (Parts D and E) Felmetatug Vedotin Felmetatug Vedotin in combination with Pembrolizumab. Felmetatug Vedotin and Pembrolizumab (Parts D and E) Pembrolizumab Felmetatug Vedotin in combination with Pembrolizumab.
- Primary Outcome Measures
Name Time Method Number of participants with adverse events (AEs) Through 30 days after last study treatment, up to approximately 5 years Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Number of participants with laboratory abnormalities Through 30-37 days after last study treatment, up to approximately 5 years Number of participants with dose limiting toxicities (DLTs) Up to 28 days Number of participants with dose limiting toxicities (DLTs) and overall safety by dose level Through 30-37 days after last study treatment; up to approximately 5 years
- Secondary Outcome Measures
Name Time Method Confirmed objective response rate (ORR) by investigator assessment Up to approximately 5 years The proportion of participants with complete response (CR) or partial response (PR) which is subsequently confirmed as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by investigator.
Complete response rate (CRR) Up to approximately 5 years The proportion of participants achieving a CR as determined by the investigator per RECIST Version 1.1.
Duration of response (DOR) Up to approximately 5 years The time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression or to death due to any cause.
Progression-free survival (PFS) Up to approximately 5 years The time from the start of any study treatment to first documentation of disease progression or to death due to any cause.
Invasive disease-free survival (iDFS) Up to approximately 5 years The time from the start of any study treatment until the date of first occurrence of one of the following events: ipsilateral invasive breast tumor (local) recurrence, regional invasive breast cancer recurrence (axilla, regional lymph nodes, chest wall, and skin of ipsilateral breast), or distant (metastatic) recurrence; contralateral invasive breast cancer; second primary non-breast invasive cancer (other than squamous of basal cell skin cancer); or death from any cause.
Pharmacokinetic (PK) parameter - Area under the curve (AUC) Through 30-37 days after last study treatment; up to approximately 3 years To be summarized using descriptive statistics.
PK parameter - Maximum concentration (Cmax) Through 30-37 days after last study treatment, up to approximately 3 years To be summarized using descriptive statistics.
PK parameter - Time to maximum concentration (Tmax) Through 30-37 days after last study treatment, up to approximately 3 years To be summarized using descriptive statistics.
PK parameter - Apparent terminal half-life (t1/2) Through 30-37 days after last study treatment, up to approximately 3 years To be summarized using descriptive statistics.
PK parameter - Trough concentration (Ctrough) Through 30-37 days after last study treatment, up to approximately 3 years To be summarized using descriptive statistics.
Incidence of antidrug antibodies (ADAs) Through 30-37 days after last study treatment, up to approximately 3 years To be summarized using descriptive statistics.
Trial Locations
- Locations (29)
UCHealth Sue Anschutz-Rodgers Eye Center
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
🇺🇸Aurora, Colorado, United States
Presbyterian/St Lukes Medical Center
🇺🇸Denver, Colorado, United States
AdventHealth Celebration Infusion Center
🇺🇸Celebration, Florida, United States
AdventHealth Medical Group Oncology Research at Celebration
🇺🇸Celebration, Florida, United States
Florida Cancer Specialists
🇺🇸Orlando, Florida, United States
Sarah Cannon Research Institute at Florida Cancer Specialists
🇺🇸Orlando, Florida, United States
Northwestern Medical Group
🇺🇸Chicago, Illinois, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Community Health Network, Inc.
🇺🇸Indianapolis, Indiana, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Sarah Cannon Research Institute - Pharmacy
🇺🇸Nashville, Tennessee, United States
The University of Texas M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
The University of Texas MD Anderson Cancer Center Investigational Pharmacy Services
🇺🇸Houston, Texas, United States
South Texas Accelerated Research Therapeutics, LLC
🇺🇸San Antonio, Texas, United States
START Mountain Region
🇺🇸West Valley City, Utah, United States
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Hamato-Onkologische Phase 1 Unit der Charite/Charite Research Organisation
🇩🇪Berlin, Germany
Istituto Europeo di Oncologia
🇮🇹Milan, Lombardia, Italy
START Madrid-Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
South Texas Accelerated Research Therapeutics Midwest
🇺🇸Grand Rapids, Michigan, United States
SCRI Oncology Partners
🇺🇸Nashville, Texas, United States
South Texas Accelerated Research Therapeutics Mountain Region
🇺🇸West Valley City, Utah, United States
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain