GOG 3063 Eligibility

Patient Inclusion Criteria

In order to qualify for participation in the study, patients must meet all of the following criteria. Inclusion criteria should be assessed by the Investigator and, when applicable (per Schedule of Assessments [SOA]) the assessment should occur within 7 days prior to expected C1D1.

1. Patient is female and ≥18 years of age.
2. Patient or patient’s legal representative (as applicable per regional requirements) has provided written informed consent.
3. Patient is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
4. Patient has histologically confirmed diagnosis of EOC, fallopian tube cancer, or primary peritoneal cancer (ie, high-grade serous, endometrioid of any grade, clear cell).
5. Patient has platinum-resistant/refractory disease, defined as disease progression within 180 days following the last administered dose of platinum therapy beyond first-line setting (resistant) or lack of response or disease progression while receiving the most recent platinum-based therapy (refractory). Patient must have progressed radiographically or by GCIG-defined CA-125 criteria on or after their most recent line of anticancer therapy beyond first-line setting.
a. Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression or the date progression was assessed by GCIG-defined CA-125 criteria, whichever comes first.
b. Note: Patients who have primary platinum-refractory or platinum-resistant disease (disease progression <3 months after completion of first-line platinum-based therapy) are excluded (see Exclusion Criterion 1).
6. Patient must have received at least 1 prior line of platinum-based therapy (as noted below) and no more than 5 prior lines of systemic anticancer therapy in the platinum-resistant setting. Patient must have received at least 1 line of therapy containing bevacizumab. The following guidelines apply:
a. Patients who have received only 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (complete response [CR] or partial response [PR]) and then progressed ≥3 to ≤6 months after the date of the last dose of platinum.
b. Prior PARP inhibitor is allowed if included within these limits of prior therapy. Prior PARP inhibitor is required for patients with a breast cancer gene (BRCA) mutation.
c. Adjuvant ± neoadjuvant is considered 1 line of therapy.
d. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered part of the preceding line of therapy (ie, not counted independently).
e. Therapy that changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently).
f. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance therapy.
7. Patient has at least one measurable lesion that qualifies as a target lesion based on RECIST v1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
8. Patient is willing provide a tumor tissue sample either collected from a prior biopsy or cytoreductive/debulking surgery occurring at any time since diagnosis or from a fresh biopsy (newly obtained tumor tissue) at Screening. A tumor tissue sample collected at Screening (fresh biopsy) is preferred. Collection of tumor tissue samples from both prior biopsy or cytoreductive/debulking surgery and fresh biopsy are recommended (when possible) to understand changes in the tumor microenvironment during treatment. Central testing of PD-L1 status will be required prior to randomization.
9. Patient has recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and/or surgery (ie, residual toxicity no worse than Grade 1 [Grade 2 treatment-associated peripheral neuropathy and/or any grade of alopecia are acceptable assuming all other inclusion criteria are met]).
10. Patient who has received prior systemic anti-neoplastic agent(s) must wait at least 5 half-lives or 4 weeks (whichever is shorter) following prior therapy before enrollment into the study or 4 weeks if the half-life of a given investigational agent is not known.
11. Patient has an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 and an estimated life expectancy of at least 3 months.
12. Patient has adequate hematologic reserve, as evidenced by:
a. Absolute neutrophil count (ANC) of ≥1,500/μL;
b. Absolute lymphocyte count of ≥500/μL;
c. Platelet count of ≥100,000/μL; and
d. Hemoglobin of ≥9 g/dL (patient may be transfused to this level if necessary, but transfusion must occur >1 week prior to the first dose of study drug[s] and hemoglobin maintained to an acceptable level [≥9 g/dL] prior to first dose).
Note: Administration of granulocyte colony-stimulating factor (G-CSF) or erythropoietin stimulating factor is permitted according to approved indications and scientific recommendations. Administration of long-acting G-CSF must occur >2 weeks prior to the first dose of study drug(s). Administration of short-acting G-CSF must occur >1 week prior to the first dose of study drug(s).
13. Patient has adequate hepatic function, as evidenced by aspartate transaminase (AST) and alanine transaminase (ALT) values ≤3 × the upper limit of normal (ULN) and serum total bilirubin values of ≤1.5 × ULN (≤2 × ULN for patients with known Gilbert’s syndrome). For patients with documented baseline liver metastasis, the following limits will apply: ≤5 × ULN for transaminase and ≤2 × ULN for bilirubin.
14. Patient has adequate renal function, as evidenced by a serum creatinine ≤1.5 × ULN or a calculated creatinine clearance of ≥45 mL/min by the Cockcroft-Gault Equation.
15. Patient has international normalized ratio (INR) and/or prothrombin time and activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case INR and/or prothrombin time and aPTT must be within the desired therapeutic range of intended use for such anticoagulants.
16. Patient agrees to abide by the contraceptive requirements detailed in the protocol.
17. Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or urine). (See Appendix 1 for the definition of WOCBP.)

Patient Exclusion Criteria

In order to qualify for participation in the study, patients must not meet any of the following criteria. Exclusion criteria should be assessed by the Investigator and, when applicable (per SOA) the assessment should occur within 7 days prior to expected C1D1.

1. Patient has primary platinum-refractory disease or primary platinum resistance, defined as disease progression during first-line platinum-based therapy (refractory) or disease progression <3 months after completion of first-line platinum-based therapy (resistant).
2. Patient has histologically confirmed diagnosis of EOC with mucinous or carcinosarcoma subtype.
3. Patient has nonepithelial tumor (eg, germline or stromal cell tumor) or ovarian tumor with low malignant potential (ie, borderline or low-grade serous tumor).
4. Patient requires recurrent (≥1 per month) fluid drainage (eg, paracentesis, thoracentesis, pericardiocentesis) or patient requires fluid drainage of ≥500 mL within 4 weeks of the expected date of the first dose of study drug.
5. Patient has received prior IL-2-based or IL-15-based cytokine therapy; patient has had exposure, including intralesional, to IL-12 or analogs thereof.
6. Patient has prior exposure to any antiPD-1/PD-L1 therapy.
7. Patient requires or has taken systemic corticosteroids (>10 mg of prednisone daily, or equivalent) within 14 days prior to the first dose of study drug(s); however, replacement doses, topical, ophthalmologic, and inhalational steroids are permitted.
8. Patient has taken non-steroid systemic immunomodulatory agents (eg, etanercept, adalimumab, etc) within 28 days prior to the first dose of study drug(s), or anticipates any use of these therapies during the study period.
9. Patient has undergone any major surgical procedure within 3 weeks prior to Screening. Patients who have not recovered from any previous surgery that occurred more than 3 weeks prior to Screening are also excluded.
10. Patient has undergone prior solid organ and/or non-autologous hematopoietic stem cell or bone marrow transplant.
11. Patient has received a live or live-attenuated vaccine(s) within 30 days prior to the first dose of study drug(s). Note: Coronavirus Disease 2019 (COVID-19) vaccine is allowed; see guidance on COVID-19 vaccines in Section 7.3.2).
12. Patient has had any active infection and/or a fever ≥38.5°C (≥101°F) within 7 days prior to the first dose of study drug(s) requiring systemic therapy. Antibiotics given for peri-procedural prophylaxis or given presumptively for a limited time (eg, until infection was ruled out), as well as topical or intra-ocular antibiotics, shall not be exclusionary.
13. Patient has active autoimmune disease(s) requiring systemic treatment within the past 2 years or a documented history of clinically severe autoimmune disease that has required chronic or frequent systemic steroids. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
14. Patient has underlying chronic lung disease, chronic obstructive pulmonary disease, metastatic lung disease, pleural effusions, or other lung disorders (eg, pulmonary embolism) with a baseline room air oxygen saturation of <92% at Screening and/or dyspnea (≥Grade 3) which requires oxygen therapy.
15. Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
16. Patient has any other concurrent uncontrolled illness or laboratory findings that may interfere with the planned treatment, affect patient compliance, such as recent serious trauma, or mental illness or substance use, which may interfere with the ability of the patient to cooperate and participate in the study.
17. Patient is at high risk of treatment-related complications, such as:
• Unstable, poorly controlled, or severe hypertension
• Clinically significant pericardial effusion
• New York Heart Association Class III or Class IV congestive heart failure (Appendix 2); high risk cardiovascular disease, defined as unstable angina. NOTE: If the Investigator plans to use PLD in the event the patient is randomized to Arm 4, patient has left ventricular ejection fraction (LVEF), as assessed by multiple gated acquisition scans (MUGA) or echocardiogram (ECHO), below the institutional lower limit of normal.
• Myocardial infarction, or cerebrovascular accident within 6 months of first dose of study drug(s)
• Uncontrolled diabetes mellitus that has required 2 or more hospitalizations in the last year and/or emergent management within the last 6 months
• Severe peripheral vascular disease
• A non-healing wound, ulcer, or bone fracture
18. Patient has had an active second malignancy within the previous 2 years. This criterion does not apply to patients with adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, urothelial carcinoma in situ, or ductal carcinoma in situ of the breast that has undergone full surgical resection.
19. Patient is currently breastfeeding or is planning to become pregnant or to begin breastfeeding during the study period or within 120 days after last study drug administration.
20. Patient has active or symptomatic central nervous system (CNS) metastases unless all the following have been met: such metastases have been treated by surgery and/or radiation therapy, and/or gamma knife and have remained radiographically stable (or shrinking) on 2 consecutive imaging examinations performed at least 6 weeks apart; and steroids have been tapered to a dose of 10 mg of prednisone (or equivalent) or less for at least 2 weeks prior to first dose of study drug(s); and the patient is neurologically stable. Patients with history of brain metastases or a suspicion of brain metastases must have a brain magnetic resonance imaging (MRI) at baseline.
21. Patient has known or suspected hypersensitivity to pembrolizumab or to any component(s) of pembrolizumab or nemvaleukin.
22. Patient has active uncontrolled coagulopathy.
23. Patient has QT interval corrected by the Fridericia Correction Formula values of >470 msec; patient who is known to have congenital prolonged QT syndromes; or patient who is on medications known to cause prolonged QT interval on ECG.
24. Patient is known to be positive for human immunodeficiency virus.
25. Patients with known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) are excluded; however, a patient with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) may be enrolled provided that HBV DNA is negative. Patients with known active hepatitis C (eg, hepatitis C virus [HCV] RNA [qualitative] are detected) are excluded; however, a patient with cured hepatitis C (negative HCV RNA status) may be enrolled.
26. History of bowel obstruction, history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 3 months before the first dose of study drug is administered. Clinical symptoms of bowel obstruction should be ruled out by appropriate imaging studies during the screening period and prior to randomization in the study. Patients with a functioning ostomy can be included in the study.
27. Subjects who are investigational site staff members directly involved in the conduct of the trial or their immediate family members, site staff members otherwise supervised by the Investigator, or subjects who are Alkermes or companies/vendors hired to be directly involved in the conduct of the study (immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted) unless the investigational site staff or staff at Alkermes or companies/vendors working on behalf of Alkermes are recusing themselves from the trial activities.