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Not yet recruitingNCT07578649Updated Sep 28, 2026

Symbiotic-GYN-18: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Chemotherapy in Adult Participants With Advanced or Recurrent MMR-proficient Endometrial Cancer

A Phase 3 interventional study of PF-08634404 and Pembrolizumab in Endometrial Neoplasms and Endometrial Cancer, sponsored by Pfizer. Not yet recruiting at 39 sites in 2 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-28.

Sponsored by Pfizer · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
600
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study 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 (with or without measurable disease) 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.
02

Conditions studied

  • Endometrial Neoplasms
  • Endometrial Cancer

Keywords

  • Recurrent Endometrial Carcinoma
  • Endometrial Neoplasms
  • Advanced Endometrial Carcinoma
  • Advanced or Recurrent Endometrial Cancer
  • pMMR
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts 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 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 1.
  • Life expectancy of at least 12 weeks.
  • Adequate organ function as defined in the protocol.

Exclusion criteria

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
600 participants (estimated)

Study arms

  • Experimental
    PF-08634404 plus Chemotherapy

    PF-08634404 plus Chemotherapy, followed by PF-08634404 maintenance therapy

    Biological: PF-08634404 · Drug: Standard of Care Chemotherapy

  • Active comparator
    Pembrolizumab plus Chemotherapy

    Pembrolizumab plus Chemotherapy, followed by Pembrolizumab maintenance therapy

    Biological: Pembrolizumab · Drug: Standard of Care Chemotherapy

Interventions

  • BiologicalPF-08634404

    Solution for IV infusion

  • BiologicalPembrolizumab

    Solution for IV infusion

    Also known as: keytruda

  • DrugStandard of Care Chemotherapy

    Solution for IV infusion

05

What researchers measure

Primary outcomes

  1. Progression-Free Survival (PFS) using RECIST v1.1 as assessed by Blinded Independent Central Review (BICR)

    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.

    Time frame: Approximately 36 months

Secondary outcomes

  1. Overall Survival (OS)

    OS is defined as the time from the date of randomization to the date of death due to any cause.

    Time frame: Approximately 56 months

  2. PFS using RECIST v1.1 as assessed by investigator

    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.

    Time frame: Approximately 36 months

  3. Objective Response Rate (ORR) as assessed by BICR and investigator

    Proportion of participants with confirmed Complete Response (CR) or Partial Response (PR) per RECIST v1.1, assessed by BICR and by investigator

    Time frame: Approximately 56 months

  4. Duration of Response (DoR) as assessed by BICR and investigator

    Time from first documented CR or PR to disease progression or death, per RECIST v1.1, assessed by BICR and by investigator

    Time frame: Approximately 56 months

  5. Number of participants with treatment-emergent adverse events

    AEs as characterized by type, frequency, intensity as graded by NCI CTCAE version 5.0, timing, seriousness, and relationship to study intervention(s)

    Time frame: Through end of the study and up to approximately 56 months

  6. Number of participants with laboratory abnormalities

    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.

    Time frame: Through end of the study and up to approximately 56 months

  7. Serum concentrations of PF-08634404

    Pre-dose and post-dose serum concentrations of PF-08634404

    Time frame: Through end of the study and up to approximately 56 months

  8. Incidence of ADA against PF-08634404

    Incidence of anti-drug antibodies (ADA) to PF-08634404

    Time frame: Through end of the study and up to approximately 56 months

  9. 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)

    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.

    Time frame: Baseline, up to approximately 56 months

  10. Change from baseline in the back pain/pelvis pain, GI symptoms, and urological symptoms scales of the EORTC QLQ EN24

    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 frame: Baseline, up to approximately 56 months

  11. Time to definitive deterioration in the global health status/QoL and physical functioning scale of the EORTC QLQ-C30.

    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

    Time frame: Approximately 56 months

06

Study locations

39 sites
  • Jupiter Medical Center/ Anderson Family Cancer Institute
    Jupiter, Florida 33458, United States
  • Minnesota Oncology Hematology, PA
    Coon Rapids, Minnesota 55433, United States
  • Minnesota Oncology Hematology, PA
    Edina, Minnesota 55435, United States
  • Minnesota Oncology Hematology, PA
    Maple Grove, Minnesota 55369, United States
  • Minnesota Oncology Hematology, PA
    Maplewood, Minnesota 55109, United States
  • Minnesota Oncology Hematology, PA
    Woodbury, Minnesota 55125, United States
  • The Center of Hope
    Reno, Nevada 89511, United States
  • Miami Valley Hospital South
    Centerville, Ohio 45459, United States
  • Northwest Cancer Specialists, P.C.
    Happy Valley, Oregon 97015, United States
  • Northwest Cancer Specialists, P.C.
    Portland, Oregon 97227, United States
  • Northwest Cancer Specialists, P.C.
    Tigard, Oregon 97223, United States
  • Sarah Cannon Research Institute- Pharmacy
    Nashville, Tennessee 37203, United States
  • SCRI Oncology Partners
    Nashville, Tennessee 37203, United States
  • Texas Oncology - West Texas
    Abilene, Texas 79606, United States
  • Texas Oncology-West Texas
    Amarillo, Texas 79124, United States
  • Texas Oncology - Central South
    Austin, Texas 78731, United States
  • Texas Oncology - Central South
    Austin, Texas 78745, United States
  • Texas Oncology - Central South
    Austin, Texas 78758, United States
  • Texas Oncology-West Texas
    El Paso, Texas 79902, United States
  • Texas Oncology - West Texas
    El Paso, Texas 79915, United States
  • Texas Oncology - West Texas
    El Paso, Texas 79938, United States
  • Texas Oncology - Central South
    Harlingen, Texas 78550, United States
  • US Oncology Investigational Products Center (IPC)
    Irving, Texas 75063, United States
  • Texas Oncology - Central South
    McAllen, Texas 78503, United States
  • Texas Oncology-West Texas
    Midland, Texas 79701, United States
  • Texas Oncology - West Texas
    Odessa, Texas 79761, United States
  • Texas Oncology - Central South
    Waco, Texas 76712, United States
  • Texas Oncology - Central South
    Weslaco, Texas 78596, United States
  • Texas Oncology-West Texas
    Wichita Falls, Texas 76310, United States
  • Virginia Oncology Associates
    Chesapeake, Virginia 23320, United States
  • Virginia Oncology Associates
    Newport News, Virginia 23606, United States
  • Virginia Oncology Associates
    Norfolk, Virginia 23502, United States
  • Virginia Oncology Associates
    Suffolk, Virginia 23435, United States
  • Virginia Oncology Associates
    Williamsburg, Virginia 23188, United States
  • Northwest Cancer Specialists, P.C.
    Vancouver, Washington 98684, United States
  • Minnesota Oncology Hematology, P.A.
    Hudson, Wisconsin 54016, United States
  • Hyogo Cancer Center
    Akashi, Hyōgo 673-8558, Japan
  • Saitama Medical University International Medical Center
    Hidaka, Saitama 350-1298, Japan
  • Cancer Institute Hospital of JFCR
    Koto-ku, Tokyo 135-8550, Japan
07

References and documents

Individual participant data

Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

08

Registry details

Key details

Study ID
NCT07578649
Lead sponsor
Pfizer
Collaborators
GOG Foundation, European Network of Gynaecological Oncological Trial Groups (ENGOT)
Responsible party
Sponsor
First posted
May 11, 2026
Start date
Oct 9, 2026 (estimated)
Primary completion
Jun 1, 2029 (estimated)
Completion
Jan 30, 2031 (estimated)
Last update
Sep 28, 2026

Study contacts

Pfizer CT.gov Call Center
Contact
ClinicalTrials.gov_Inquiries@pfizer.com
1-800-718-1021
Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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