Ovarian Cancer
Conditions
Brief summary
To learn if adding etigilimab to nivolumab therapy can help to control clear cell ovarian, fallopian tube, and primary peritoneal cancers that are resistant to platinum-based therapy
Detailed description
Primary Objectives: 1. To estimate the objective response rate of the combination of etigilimab and nivolumab in patients with platinum resistant clear cell ovarian cancer. 2. To evaluate the toxicity of the combination of etigilimab and nivolumab in patients with platinum resistant clear cell ovarian cancer. Secondary Objectives: 1. To determine PFS of the combination of etigilimab and nivolumab in patients with platinum resistant clear cell ovarian cancer. 2. To estimate the disease control rate of the combination of etigilimab and nivolumab in patients with platinum resistant clear cell ovarian cancer. 3. To investigate molecular and immunological changes associated with the combination of TIGIT and PD-1 inhibition; specifically to describe changes in T cell populations (including but not limited to CD3, CD8, CD4, FOXP3) and cell proliferation, as well as report changes in the proportion of macrophage phenotypes M1 and M2 (with phenotypic markers potentially including arginase1, CD11b, PDL-1, and CD206) 4. To determine feasibility of interrogating the gut microbial signatures and dietary patterns in an ovarian cancer cohort. 5. Identify components and determinants of the gut microbiome that could modulate toxicity or provide a signature of excellent or poor response to cancer immunotherapy.
Interventions
DRUGNivolumab
Given by IV (vein)
DRUGEtigilimab
Given by IV (vein)
Sponsors
M.D. Anderson Cancer Center
Mereo BioPharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria will be assessed within 28 days of starting study treatment: 1. Ability to provide signed informed consent. 2. Age ≥ 18 years at time of study entry. 3. Willingness and ability to comply with the protocol for the duration of the study including undergoing treatment, biopsy, and scheduled visits and examinations including follow up. 4. Histology showing recurrent clear cell ovarian, peritoneal, or fallopian tube cancer. 5. Platinum resistant or refractory disease as defined by progression of disease on a platinum- containing regimen or recurrence of disease within 180 days of previous platinum treatment. Have measurable disease based on modified RECIST 1.1. For the purposes of this study measurable disease is defined at least one "target lesion" that can be accurately measured in at least one dimension (longest dimension to be recorded). Each target lesion must be \>20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or \>10 mm when measured by spiral CT. The target lesion must be distinct from other tumor areas selected for pre-treatment biopsies. Pre- treatment imaging must be performed within 4 weeks of starting therapy. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Adequate normal organ and marrow function as defined below. 1. Hemoglobin ≥9.0 g/dL. 2. Absolute neutrophil count (ANC) \> 1500/mm3. 3. Platelet count ≥100 x 109/L (\>75,000/mm3). 4. Serum bilirubin ≤1.5 x ULN. This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. 5. AST (SGOT)/ALT (SGPT) ≤2.5 x ULN unless liver metastases are present, in which case it must be * 5x ULN. 6. Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Creatinine CL (mL/min) * Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL) 9. Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply: 1. Women \<50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post- menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). 2. Women ≥50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 10. Has primary central nervous system (CNS) malignancy or known unrelated/active CNS metastases and/or carcinomatous meningitis. <!-- --> 1. Subjects with previously treated, asymptomatic brain metastases may participate provided they meet the following criteria: clinically stable for at least 4 weeks and have no evidence of new or enlarging brain metastases and are off steroids 14 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study drug. 2. Subjects with asymptomatic brain metastases (ie, no neurological symptoms, no requirements for corticosteroids, and no lesion \>1.5 cm) may participate but will require regular imaging of the brain as a site of disease. 3. Subjects with CNS symptoms should undergo a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain to exclude new or progressive brain metastases. Spinal cord metastasis is acceptable. However, subjects with spinal cord compression must be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate of the Combination of Etigilimab and Nivolumab in Patients With Platinum Resistant Clear Cell Ovarian Cancer. | 39 months | Clinical benefit was defined as objective response or stable disease (SD) for greater than or equal to 4 months. Best overall response will be used for estimating Objective Response Rate, Complete Response (CR) + Partial Response (PR). |
| The Toxicity of the Combination of Etigilimab and Nivolumab in Patients With Platinum Resistant Clear Cell Ovarian Cancer. | 39 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response of the Combination of Etigilimab and Nivolumab in Patients With Platinum Resistant Clear Cell Ovarian Cancer | 39 months | Duration of Response is defined as time from first treatment to documented disease progression. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShannon Westin, MD
M.D. Anderson Cancer Center
Participant flow
Recruitment details
The total recruitment time for this study was 51 months, from October 2021 to January 2025.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 53.6 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 5 / 23 |
Outcome results
None listed