A Study of Durvalumab With or Without Tremelimumab in Endometrial Cancer

NCT03015129 | Completed Phase 2 Results DMC

• 1 other identifier: 16-1491
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 7

Brief Summary

This study will test the safety and efficacy of the experimental drug called durvalumab with or without another experimental drug called tremelimumab in endometrial cancer. Radiologic tumor assessment will be repeated every 8 weeks +/- 7 days for the first 48 weeks and then every 12 weeks +/- 7 days until PD. For patients who remain progression free 2 years post completion of protocol directed treatment, every 6 months +/- 1 month. irRECIST assessments will only be completed for patients continuing treatment beyond PD.

Conditions

Endometrial Cancer; Endometrial Carcinosarcoma; Endometrial Carcinoma; Endometrial Cancer Recurrent; Endometrial Carcinoma, Recurrent

Keywords

Durvalumab; MEDI4736; Tremelimumab; anti-PD-L1 Antibody; anti-CTLA-4 antibody; 16-1491

Outcome Measures

Primary Outcomes (1)

• Treatment Efficacy Determined by Measuring the Overall Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

  Up to 72 months

Study Arms (2)

Durvalubmab

EXPERIMENTAL

Patients will receive intravenous infusion of durvalumab 1500mg Fixed Dose every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.

Drug: Durvalumab

Durvalubmab + Tremelimumab

EXPERIMENTAL

Patients will receive 1500mg Flat Dose durvalubmab via intravenous infusion every 4 weeks for up to 4 cycles and 75mg tremelimumab via intravenous infusion every 4 weeks for up to 4 cycles, and then continue 1500mg Fixed Dose durvalumab every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

Durvalubmab; Durvalubmab + Tremelimumab

Tremelimumab DRUG

Durvalubmab + Tremelimumab

Eligibility Criteria

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

You may qualify if:

• Subjects must have recurrent or persistent endometrial carcinoma (including: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma) or endometrial carcinosarcoma). Histologic documentation of diagnosis of carcinoma is required. MSI-high patients will be identified based on immunohistochemistry or MSI testing of archival tumor specimens by department of pathology or via known mutations found in mismatch repair genes via the Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) assay through MSKCC IRB# 12-245.
• All patients must have measurable disease. Measurable disease is defined by RECIST (version 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.
• Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Age ≥ 18 years and life expectancy of ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Resolution of (non-laboratory) adverse effects of recent surgery, radiotherapy, or chemotherapy to Grade ≤1 prior to first study treatment (with the exception of alopecia or neuropathy).
• Patients must have had one prior platinum-based chemotherapeutic regimen for management of endometrial carcinoma or carcinosarcoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen.
• Patients are allowed to receive, but are not required to receive, three additional cytotoxic regimen for management of recurrent or persistent disease. Hormonal therapies will not count toward the prior regimen limit.
• Adequate normal organ and marrow function defined by the following laboratory results obtained within 14 days prior to first treatment:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (\> 1500 per mm\^3)
• Platelet ≥ 100 x 10\^9/L (\>100,000 per mm\^3)
• Hemoglobin ≥ 9.0 g/dL
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (Unless Gilbert's Syndrome,for which Bilirubin ≤ 3 x institutional upper limit of normal (ULN) without concurrent clinically significant liver disease)
• AST (SGOT)/ALT (SGPT) ≤ 3 x institutional upper limit of normal unless (ULN) unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site); Previous enrollment in the present study.
• Participation in another clinical study with receipt of an investigational product during the last 4 weeks
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or any anti-CTLA4, including tremelimumab.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease (eg, cervical cancer in situ)
• Adequately treated stage 1 breast cancer.
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) \< 21 days prior to the first dose of study drug. Receipt of the last dose of hormonal therapy within \< 7 days prior to the first dose of study drug.
• Any prior radiation therapy must be discontinued at least four weeks prior to registration.
• At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy) There is no delay in treatment for minor procedures (e.g., central venous access catheter placement).
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs)
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or durvalumab and tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone for nausea or steroids as CT scan contrast premedication) may be enrolled.
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> Grade 1
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (2)

• Di Dio C, Bogani G, Di Donato V, Cuccu I, Muzii L, Musacchio L, Scambia G, Lorusso D. The role of immunotherapy in advanced and recurrent MMR deficient and proficient endometrial carcinoma. Gynecol Oncol. 2023 Feb;169:27-33. doi: 10.1016/j.ygyno.2022.11.031. Epub 2022 Dec 6.

  PMID: 36493574 DERIVED

• Antill Y, Kok PS, Robledo K, Yip S, Cummins M, Smith D, Spurdle A, Barnes E, Lee YC, Friedlander M, Baron-Hay S, Shannon C, Coward J, Beale P, Goss G, Meniawy T, Lombard J, Andrews J, Stockler MR, Mileshkin L; Australia New Zealand Gynaecological Oncology Group (ANZGOG). Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial. J Immunother Cancer. 2021 Jun;9(6):e002255. doi: 10.1136/jitc-2020-002255.

  PMID: 34103352 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Endometrial Neoplasms; Recurrence

Interventions

durvalumab; tremelimumab

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Vicky Makker, MD
• Organization: Memorial Sloan Kettering Cancer Center

makkerv@mskcc.org

646-888-4224

Study Officials

• Vicky Makker, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 9, 2017
• Study Start: January 1, 2017
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: February 6, 2024
• Results First Posted: February 6, 2024

Record last verified: 2023-01

Locations

US (7)