| Eligibility |
Inclusion Criteria:
- Ability to provide signed informed consent
- Age >= 18 years at time of study entry
- 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
- Histology showing recurrent clear cell ovarian, peritoneal, or fallopian tube cancer
- 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 Response Evaluation Criteria in Solid Tumors
(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.
Pretreatment imaging must be performed within 4 weeks of starting therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Hemoglobin >= 9.0 g/dL (within 28 days of starting study treatment)
- Absolute neutrophil count (ANC) > 1500/mm^3 (within 28 days of starting study
treatment)
- Platelet count >=100 x 10^9/L (> 75,000/mm^3) (within 28 days of starting study
treatment)
- Serum bilirubin =< 1.5 x upper limit of normal (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 (within 28 days of starting study
treatment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =<
2.5 x ULN unless liver metastases are present, in which case it must be =< 5 x ULN
(within 28 days of starting study treatment)
- 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 (within 28 days of starting study
treatment)
- 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
amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
- Women < 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the postmenopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy)
- Women >= 50 years of age would be considered post-menopausal if they have been
amenorrheic 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)
Exclusion Criteria:
- Participation in another clinical study with an investigational product during the
last 28 days
- Prior treatment with CD137 agonists, anti-TIGIT antibody, anti-CTLA-4 or anti-PDL1/PD1
antibodies
- 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
- Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine
therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies) =< 28 days prior to the first dose of study drug. If sufficient wash-out
time has not occurred due to the schedule or pharmacokinetic (PK) properties of an
agent, a longer wash-out period will be required, as agreed by study sponsors and the
investigator
- Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria
for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria
- Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis
after consultation with the primary investigator
- 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
- Any concurrent chemotherapy, investigational produce (IP), biologic, or hormonal
therapy for cancer treatment
- 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
- History of allogenic organ transplantation
- 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
criterion
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only
after consultation with the primary investigator
- Patients with celiac disease controlled by diet alone
- 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 adverse events (AEs) or compromise the ability of the patient to
give written informed consent
- Any medical, social, or psychological condition that would interfere with evaluation
of study treatment or interpretation of patient safety or study results
- Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and tuberculosis [TB] testing
in line with local practice), hepatitis B (known positive hepatitis B virus [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 ribonucleic acid (RNA)
- History of another primary malignancy except for the following histories.
- 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
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
- Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- 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
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) >= 470 ms
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of trial therapies. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- 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
- 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
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients
- Unresolved partial or complete small or large bowel obstruction
- 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
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