Trial Title:
EON: A Single-arm Phase II Study of Etigilimab (OMP-313M32) in Combination With Checkpoint Inhibition (Nivolumab) in Patients With Platinum-resistant, Recurrent Epithelial Ovarian Cancer
NCT ID:
NCT05715216
Condition:
Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Nivolumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Given by IV (vein)
Arm group label:
Etigilimab plus Nivolumab
Other name:
BMS-936558
Other name:
Opdivo
Intervention type:
Drug
Intervention name:
Etigilimab
Description:
Given by IV (vein)
Arm group label:
Etigilimab plus Nivolumab
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.
Criteria for eligibility:
Criteria:
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.
Exclusion Criteria:
Exclusion criteria will be assessed within 28 days of starting study treatment and is
listed below.
1. Participation in another clinical study with an investigational product during the
last 28 days.
2. Prior treatment with CD137 agonists, anti-TIGIT antibody, anti-CTLA-4 or
anti-PDL1/PD1 antibodies.
3. Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study.
4. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization,
monoclonal antibodies) ≤28 days or 5 half-lives, whichever is shorter, prior to the
first dose of study drug. If sufficient wash-out time has not occurred due to the
schedule or PK properties of an agent, a longer wash-out period will be required, as
agreed by study sponsors and the investigator.
5. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria.
1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis
after consultation with the primary investigator.
2. Patients with irreversible toxicity not reasonably expected to be exacerbated
by treatment with investigational therapy may be included only after
consultation with the primary investigator.
6. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
7. Major surgical procedure (as defined by the Investigator) within 28 days prior to
the first dose of IP. Note:
Local surgery of isolated lesions for palliative intent is acceptable.
8. History of allogenic organ transplantation.
9. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to
this criteria.
a. Patients with vitiligo or alopecia. b. Patients with hypothyroidism (e.g.,
following Hashimoto syndrome) stable on hormone replacement.
c. Any chronic skin condition that does not require systemic therapy. d. Patients
without active disease in the last 5 years may be included but only after
consultation with the primary investigator. e. Patients with celiac disease
controlled by diet alone.
10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially
increase risk of incurring AEs or compromise the ability of the patient to give
written informed consent.
11. Any medical, social, or psychological condition that would interfere with evaluation
of study treatment or interpretation of patient safety or study results.
12. Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is
negative for HCV RNA.
13. History of another primary malignancy except for the following histories.
1. Malignancy treated with curative intent and with no known active disease ≥5
years before the first dose of IP and of low potential risk for recurrence.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
14. History of leptomeningeal carcinomatosis.
15. Brain metastases or spinal cord compression. Patients with suspected brain
metastases at screening should have a MRI (preferred) or CT each preferably with
intravenous (IV) contrast of the brain prior to study entry.
16. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms.
17. Current or prior use of immunosuppressive medication within 14 days before the first
dose of trial therapies. Listed below are the exceptions to this criterion.
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent.
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication).
18. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and
up to 90 days after the last dose of IP.
19. Female patients who are pregnant or breastfeeding or of reproductive potential who
are not willing to employ effective birth control from screening to 180 days after
the last dose of Nivolumab/Etigilimab combination therapy.
20. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
21. Unresolved partial or complete small or large bowel obstruction.
22. Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions and
requirements.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shannon Westin, MD
Phone:
713-794-4314
Email:
swestin@mdanderson.org
Investigator:
Last name:
Shannon Westin, MD
Email:
Principal Investigator
Start date:
March 24, 2023
Completion date:
April 30, 2025
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Mereo BioPharma
Agency class:
Industry
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05715216
http://www.mdanderson.org
