Endometrial Neoplasms, Endometrial Cancer
Conditions
Keywords
Recurrent Endometrial Carcinoma, Endometrial Neoplasms, Advanced Endometrial Carcinoma, Advanced or Recurrent Endometrial Cancer, pMMR
Brief summary
This study is being conducted to assess whether the study medicine PF 08634404, given in combination with chemotherapy, improves outcomes compared with another medicine called pembrolizumab plus chemotherapy. Chemotherapy is a type of cancer treatment that uses medicines to destroy cancer cells or stop them from growing. Our bodies have a built-in DNA "spell-checker," called the mismatch repair (MMR) system, that fixes genetic mistakes. In most endometrial cancers, this system works normally, and these cancers are called MMR-proficient (pMMR). However, pMMR tumors are harder for the immune system to recognize and attack. When endometrial cancer has spread beyond the uterus or comes back after previous treatment, it is called advanced or recurrent endometrial cancer. This study is for adults with mismatch repair-pMMR advanced or recurrent endometrial cancer. Participants must meet key criteria, including: * Women who are 18 years or older, and not pregnant at the time of joining the study * pMMR endometrial cancer only * Measurable Stage III disease, Stage IV disease (with or without measurable disease) per FIGO staging, a system doctors use to describe how far cancer has spread in the body, or recurrent endometrial cancer * Has not received chemotherapy except for chemotherapy given after the main surgery and more than 6 months before relapse * Be in good enough health to receive study treatment. Approximately 600 adult women will be enrolled. Each participant will be randomly assigned (like a flip of the coin) to one of two treatment groups, with about half in each group. The study is open, meaning both the doctors and participants know what treatment is being given. Participants will receive their assigned treatment through intravenous infusions (medicine is given directly into a vein). The treatment will be given in cycles. Experimental Group will receive new study medicine called PF-08634404 plus chemotherapy. It will be followed by PF 08634404 alone for up to 2 years (35 cycles). Control Group will receive an approved medicine called pembrolizumab plus chemotherapy. It will be followed by pembrolizumab alone for up to 2 years (20 cycles). The study will include regular visits for: * Participants will have regular visits to the study site for treatment, health checks, and tests. * After stopping treatment, participants will come for a final visit within a month to check their health and review any reactions. * Follow-up will continue every 12 weeks by phone or in person or by reviewing health records. This helps check health and any new treatments. * Tests will be done every 9 weeks during the first 104 weeks to see how the cancer is responding. After that, tests will be done every 12 weeks.
Interventions
BIOLOGICALPF-08634404
Solution for IV infusion
BIOLOGICALPembrolizumab
Solution for IV infusion
Solution for IV infusion
Sponsors
Pfizer
GOG Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study, both the participants and the study team will know whether the participants are receiving PF-08634404 or Pembrolizumab.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women ≥18 years of age who are confirmed not pregnant at screening. * Histologically or cytologically confirmed endometrial cancer that is recurrent or advanced; carcinosarcomas are eligible but pure sarcomas are excluded. * Newly diagnosed FIGO Stage III disease with measurable disease per RECIST v1.1, newly diagnosed FIGO Stage IV disease with or without measurable disease, or recurrent disease with or without measurable disease per RECIST v1.1 for which curative treatment with surgery and/or radiotherapy is unlikely. * For participants with recurrent disease, prior adjuvant systemic anti-cancer therapy is allowed if relapse occurred more than 6 months after the last dose. * Must provide tumor tissue for prospective central assessment of MMR and p53 status. * Proficient mismatch repair (pMMR) endometrial cancer as determined by central testing. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Life expectancy of at least 12 weeks. * Adequate organ function as defined in the protocol.
Exclusion criteria
* Prior systemic therapy for first-line advanced or recurrent endometrial cancer. * Prior immunotherapy or anti-angiogenic therapy. * Deficient mismatch repair (dMMR) endometrial cancer by central testing. * Active or untreated central nervous system (CNS) metastases; participants with previously treated and clinically stable brain metastases may be eligible if not requiring steroids and without evidence of progression. * Clinically significant risk of bleeding or fistula, including a history of severe bleeding disorders. * History of another malignancy within 3 years, except for cancers with negligible risk of recurrence or death. * History of allogeneic organ or hematopoietic stem cell transplantation; active autoimmune disease requiring systemic treatment within the past 2 years; or history of immunodeficiency * Interstitial lung disease, pneumonitis, or clinically significant pulmonary disease * Uncontrolled or significant cardiovascular, metabolic, renal, hepatic, or vascular disease * Active or uncontrolled infection. * Recent major surgery or severe trauma within protocol-defined washout periods.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) using RECIST v1.1 as assessed by Blinded Independent Central Review (BICR) | Approximately 36 months | PFS by BICR is defined as the time from the date of randomization to the date of first documented disease progression per RECIST v1.1 as assessed by BICR, or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Approximately 56 months | OS is defined as the time from the date of randomization to the date of death due to any cause. |
| PFS using RECIST v1.1 as assessed by investigator | Approximately 36 months | PFS by investigator is defined as the time from the date of randomization to the date of first documented disease progression per RECIST v1.1 as assessed by investigator, or death due to any cause, whichever occurs first. PFS by investigator will be analyzed with the same methodology as for PFS by BICR. |
| Objective Response Rate (ORR) as assessed by BICR and investigator | Approximately 56 months | Proportion of participants with confirmed Complete Response (CR) or Partial Response (PR) per RECIST v1.1, assessed by BICR and by investigator |
| Duration of Response (DoR) as assessed by BICR and investigator | Approximately 56 months | Time from first documented CR or PR to disease progression or death, per RECIST v1.1, assessed by BICR and by investigator |
| Number of participants with treatment-emergent adverse events | Through end of the study and up to approximately 56 months | AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s) |
| Number of participants with laboratory abnormalities | Through end of the study and up to approximately 56 months | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. For laboratory tests without CTCAE grade definitions, results will be categorized as normal, high, low, or not done and be listed. |
| Serum concentrations of PF-08634404 | Through end of the study and up to approximately 56 months | Pre-dose and post-dose serum concentrations of PF-08634404 |
| Incidence of ADA against PF-08634404 | Through end of the study and up to approximately 56 months | Incidence of anti-drug antibodies (ADA) to PF-08634404 |
| Change from baseline in the global health status/quality of life (QoL) and physical functioning scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Baseline, up to approximately 56 months | The EORTC QLQ-C30 is a questionnaire for quantitative measure of health-related quality of life pertinent to participants with a broad range of cancers who are participating in international clinical trials. The core instrument is a 30-item questionnaire consisting of the following: * 5 Functional scales (physical, role, cognitive, emotional, social) * 3 Symptom scales (fatigue, pain, nausea, and vomiting, shortness of breath, loss of appetite, sleep disturbance, constipation, diarrhea) and financial impact of the disease * 2 Global items (global health status, overall HRQoL) All of the scales and single-item measures range in score from 0 to 100. High scale score represents a higher response level. |
| Change from baseline in the back pain/pelvis pain, GI symptoms, and urological symptoms scales of the EORTC QLQ EN24 | Baseline, up to approximately 56 months | The Endometrial Cancer Module (EORTC QLQ-EN24) is a disease-specific measure that is supplemental to the EORTC QLQ-C30 to capture patient's experiences with endometrial cancer-specific symptoms and impacts. The recall period is the past week. The 24-item questionnaire consists of the following: * Symptom scales/items (Lymphoedema, urological symptoms, gastrointestinal symptoms, poor body image, and sexual/vaginal problems, pain in back and pelvis, tingling/numbness, muscular pain, hair loss, and taste change) * Functional scales (sexual interest, sexual activity, and sexual enjoyment) Higher scores for functional scales represent high level of functioning, while higher scores for symptoms scales represent higher levels of symptoms/problems. |
| Time to definitive deterioration in the global health status/QoL and physical functioning scale of the EORTC QLQ-C30. | Approximately 56 months | The European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30), is a validated 30-item self-administered core questionnaire designed to assess HRQoL, functioning, and symptoms in all cancer patients or survivors. Time to deterioration is defined as time from baseline (defined as day 1 of cycle 1 before first application of maintenance therapy) to the date of the first clinically meaningful deterioration i.e. a decrease by ≥10 points for the functional scales and an increase by ≥ 10 points for the symptom scales or death in: * Physical functioning score * Role functioning score |
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed