Cervical Cancer
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Trophoblast Cell Surface Antigen 2 (TROP2)
Brief summary
Researchers are looking for new ways to treat metastatic cervical cancer. Cervical cancer is cancer in the cervix, the lower part of the uterus (womb). Metastatic means the cancer has spread to other parts of the body. Researchers want to learn about giving the study medicine sacituzumab tirumotecan (also called sac-TMT or MK-2870) along with pembrolizumab and bevacizumab treatments. Sac-TMT is an antibody drug conjugate, which is a type of medicine that attaches to specific targets on cancer cells and delivers treatment to destroy those cells. The goals of this study are to learn: * About the safety of sac-TMT with pembrolizumab and bevacizumab, and if people tolerate them when given together, and * If people who receive sac-TMT and pembrolizumab, with or without bevacizumab, live longer overall or without their cancer getting worse as compared to those who receive standard treatment
Detailed description
This is a 2-part study. In Part 1 Safety Run-in, eligible participants will be allocated to treatment with sac-TMT + pembrolizumab + bevacizumab. In Part 2, all participants receive standard of care induction treatment. Eligible participants whose cancer does not progress then begin maintenance treatment and are randomized to receive pembrolizumab or sac-TMT + pembrolizumab. All participants in Part 2 maintenance treatment may also receive bevacizumab at the investigator's discretion.
Interventions
BIOLOGICALPembrolizumab
Intravenous (IV) Infusion
BIOLOGICALSacituzumab Tirumotecan
IV Infusion
BIOLOGICALBevacizumab
IV Infusion
DRUGPaclitaxel
IV Infusion
DRUGCisplatin
IV Infusion
DRUGCarboplatin
IV Infusion
Participants receive the following rescue medications prior to sac-TMT infusion, per approved product label: histamine-1 receptor antagonist, histamine-2 receptor antagonist, acetaminophen or equivalent, and dexamethasone or equivalent. Participants are also recommended to receive prophylactic steroid mouthwash (dexamethasone or equivalent).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Participants in Part 1 Safety Run-in are allocated to a single treatment arm. Participants in study Part 2 complete induction treatment and are then randomized to 1 of 2 maintenance treatment arms.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has a histologically confirmed diagnosis of squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of cervix * Has persistent, recurrent, or newly diagnosed metastatic cervical cancer that is not amenable to curative treatment (surgery and/or radiation) * If infected with human immunodeficiency virus (HIV), has well controlled HIV on antiretroviral therapy * If positive for hepatitis B surface antigen, has received hepatitis B virus (HBV) antiviral therapy and has undetectable HBV viral load * If has a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load * Has an Eastern Cooperative Oncology Group performance status of 0 or 1 * Has tumor programmed cell death ligand 1 expression of combined positive score ≥1 The main
Exclusion criteria
include but are not limited to the following: * Has HIV infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing * Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea) * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease * Has received prior systemic anticancer therapy other than what is specified in this protocol * Is currently receiving a strong inducer/inhibitor of cytochrome P450 3A4 that cannot be discontinued for the duration of treatment with sac-TMT * Has a diagnosis of immunodeficiency * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years * Has known active central nervous system metastases and/or carcinomatous meningitis * Has active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid) is allowed * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Has a history of stem cell/solid organ transplant * Has not adequately recovered from major surgery or has ongoing surgical complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 Safety Run-in: Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 71 months | An AE is 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. |
| Part 1 Safety Run-in: Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 68 months | An AE is 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. |
| Part 2 Maintenance Treatment: Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) | Up to approximately 48 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first, as assessed by RECIST 1.1 as evaluated by BICR. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented. |
| Part 2 Maintenance Treatment: Overall Survival (OS) | Up to approximately 60 months | OS is defined as time from randomization to death due to any cause. OS will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2 Maintenance Treatment: Progression-free Survival 2 (PFS2) as Assessed by the Investigator | Up to approximately 60 months | PFS2 is defined as the time from randomization to the documented subsequent objective disease progression after initiation of new anticancer therapy or death due to any cause, whichever occurs first. PFS2 as assessed by the investigator will be presented. |
| Part 2 Maintenance Treatment: Number of Participants Who Experience One or More AEs | Up to approximately 64 months | An AE is 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. |
| Part 2 Maintenance Treatment: Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 61 months | An AE is 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. |
| Part 2 Maintenance Treatment: Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status and Quality of Life Combined Score | Baseline and up to approximately 58 months | EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1 = Very poor to 7 = Excellent). The combined score of GHS and QoL is computed by averaging the raw scores of the 2 questions and then applying a linear transformation to standardize the average score, so that the combined score ranges from 0 to 100. A higher score indicates a better outcome. The change from baseline in the EORTC QLQ-C30 GHS and QoL combined score will be presented. |
| Part 2 Maintenance Treatment: Change from Baseline in EORTC QLQ-C30 Physical Functioning Combined Score | Baseline and up to approximately 58 months | EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1 = Not at All to 4 = Very Much). The combined score is computed by averaging the raw scores of the 5 questions and then applying a linear transformation to standardize the average score, so that the combined score ranges from 0 to 100. A higher score indicates a better outcome. The change from baseline in the EORTC QLQ-C30 physical functioning combined score will be presented. |
| Part 2 Maintenance Treatment: Change from Baseline in EORTC QLQ-C30 Role Functioning Combined Score | Baseline and up to approximately 58 months | EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1 = Not at All to 4 = Very Much). The combined score is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined score ranges from 0 to 100. A higher score indicates a better outcome. The change from baseline in the EORTC QLQ-C30 role functioning combined score will be presented. |
Countries
Argentina, Belgium, Canada, Czechia, Hungary, Israel, Italy, Japan, Poland, South Korea, Spain, Sweden, Taiwan, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed