Avelumab in Patients With MSS, MSI-H and POLE-mutated Recurrent or Persistent Endometrial Cancer and of Avelumab/Talazoparib and Avelumab/Axitinib in Patients With MSS Recurrent or Persistent Endometrial Cancer

NCT02912572 | Active Not Recruiting Phase 2 Results DMC

• 1 other identifier: 16-322
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is evaluating a drug called Avelumab alone and in combination with Talazoparib or Axitinib as a possible treatment for recurrent or metastatic endometrial cancer.

Conditions

Metastatic Endometrial Cancer

Keywords

Endometrial Cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate

  The objective response rate was determined by the frequency of patients who had objective tumor response, determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI, where objective response represents either a confirmed complete response (CR; disappearance of all target lesions) or a confirmed partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters); objective response = CR + PR.

  Up to 39 months

• Progression-Free Survival at 6 Months

  Progression-free survival at 6 months was determined by the frequency of patients who survived progression-free for at least 6 months after initiating study treatment by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), where disease progression represents at least a 20% increase in the sum of diameters of target lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.

  6 months

Secondary Outcomes (3)

• Progression-Free Survival

  Interval from start of treatment to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurs first.

• Overall Survival

  Participants are followed for survival status from registration through up to 3 years after removal from study intervention

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  Adverse event data was collected for all participants through 30 days after last intervention

Study Arms (4)

Pole Mutated Endometrial Cancer

EXPERIMENTAL

Participants with Pole mutated endometrial cancer Avelumab will be administered intravenously twice per cycle

Drug: Avelumab

MSS Endometrial Cancer

EXPERIMENTAL

Participants with MSS mutated endometrial cancer Avelumab will be administered intravenously twice per cycle

Drug: Avelumab

MSS Avelumab/Talazoparib Combination Arm

EXPERIMENTAL

Participants with MSS mutated endometrial cancer Avelumab will be administered intravenously twice per cycle Talazoparib will be administered one time per day by mouth

Drug: Avelumab; Drug: Talazoparib

MSS Avelumab/Axitinib Combination Arm

EXPERIMENTAL

Participants with MSS mutated endometrial cancer Avelumab will be administered intravenously twice per cycle Axitinib will be administered twice per day by mouth

Drug: Avelumab; Drug: Axitinib

Interventions

Avelumab DRUG

Avelumab will be administered intravenously twice per cycle Each Cycle lasts 28 days Premedication Antihistamine and Paracetamol will be administered prior to treatment

MSS Avelumab/Axitinib Combination Arm; MSS Avelumab/Talazoparib Combination Arm; MSS Endometrial Cancer; Pole Mutated Endometrial Cancer

Talazoparib DRUG

Talazoparib will be taken one time per day by mouth Each Cycle lasts 28 days

MSS Avelumab/Talazoparib Combination Arm

Axitinib DRUG

Axitinib will be taken twice per day by mouth Each Cycle lasts 28 days

MSS Avelumab/Axitinib Combination Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be classified into one of the following cohorts of recurrent or persistent endometrial cancer of any histology:
• The MSI/POLE cohort includes endometrial cancers that are:
• MSI-H as determined by immunohistochemical complete loss of expression (absence of nuclear immunoreactivity) of at least one of the mismatch repair genes MSH2, MSH6, MLH1 and PMS2. This test is now done routinely for every newly diagnosed endometrial cancer patient in most centers in the US.
• And/OR:
• POLE-mutated, i.e. endometrial cancers known to harbor mutations in the exonuclease domain (amino acid residues 268-471) of polymerase e (POLE) as determined by targeted sequencing or other next generation sequencing assay. Any Clinical Laboratory Improvement Amendments (CLIA)-approved genomic test documenting mutations in the exonuclease domain of POLE gene (amino acid residues 268-471) in the tumor will be accepted as proof of presence of POLE mutations and will lead to classification into this patient cohort.
• The MSS cohorts include:
• Endometrial cancers that are MSS as determined by normal immunohistochemical nuclear expression of all the mismatch repair genes MSH2, MSH6, MLH1 and PMS2. Tumors which have not been sequenced for POLE mutations (i.e. their POLE mutations status is unknown) but are MSS, will be included in this cohort.
• All patients must have measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be \>= 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or \>= 20 mm when measured by chest x-ray. Lymph nodes must be \> 15 mm in short axis when measured by CT or MRI.
• Prior Therapy:
• There is no upper limit of prior therapies but patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy. Any platinum based chemotherapy (single agent platinum or any platinum doublet) administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen. Furthermore, patients who have only received chemotherapy in the adjuvant setting will be eligible for the study.
• Prior hormonal therapy is allowed.
• Patients must NOT have received any class of drugs targeted to the PD-1/PD-L1 pathway.
• Patients must NOT have received any prior PARP inhibitor therapy (for patients being considered for the avelumab/talazoparib cohort only).
• Patients must NOT have received prior axitinib (for patients being considered for the avelumab/axitinib cohort only).
• Age of 18 or greater years. Because insufficient dosing or adverse event data are currently available on the use of Avelumab, talazoparib, and/or axitinib in participants \< 18 years of age, children are excluded from the study. Endometrial cancer is very rare in the pediatric population.

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participants who are receiving any other investigational agents.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to avelumab or any component in its formulations, or compounds of similar chemical or biologic composition to avelumab. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• Participants with a history of treatment with an anti-PD-1, anti-PD-L1, anti-CTLA-4 or other investigational agents that target immune checkpoint inhibitors.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness, which may compromise the efficacy of immunostimulatory therapy.
• Positive test for HBV surface antigen
• Positive Hepatitis C antibody and positive confirmatory HCV RNA test. The confirmatory HCV RNA test is not required if the HCV antibody is negative. If Hepatitis C antibody is positive, the confirmatory HCV RNA test should be done and if it is negative, then participants are eligible.
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
• Active infection requiring systemic therapy.
• Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection);
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Prior organ transplantation including allogeneic stem-cell transplantation.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Pfizer: collaborator

Study Sites (4)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Konstantinopoulos PA, Gockley AA, Xiong N, Krasner C, Horowitz N, Campos S, Wright AA, Liu JF, Shea M, Yeku O, Castro C, Polak M, Lee EK, Sawyer H, Bowes B, Moroney J, Cheng SC, Tayob N, Bouberhan S, Spriggs D, Penson RT, Fleming GF, Nucci MR, Matulonis UA. Evaluation of Treatment With Talazoparib and Avelumab in Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer. JAMA Oncol. 2022 Sep 1;8(9):1317-1322. doi: 10.1001/jamaoncol.2022.2181.

  PMID: 35900726 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

avelumab; talazoparib; Axitinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Panagiotis Konstantinopoulos
• Organization: Dana-Farber Cancer Institute

Panagiotis_Konstantinopoulos@dfci.harvard.edu

617-632-5269

Study Officials

• Panagiotis Konstantinopoulos, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 20, 2016
• First Posted: September 23, 2016
• Study Start: November 14, 2016
• Primary Completion: November 15, 2023
• Study Completion (Estimated): November 1, 2026
• Last Updated: July 10, 2025
• Results First Posted: July 5, 2024

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)