A Phase 3, Multicenter, Open-Label, Randomized Study of Nemvaleukin Alfa in Combination With Pembrolizumab Versus Investigator's Choice Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARTISTRY-7)

1. Patient is female and >=18 years of age.
2. Patient or patient's legal representative is willing and able to provide
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 (i.e., high-grade
serous, endometrioid of any grade, clear cell), fallopian tube cancer, or
primary peritoneal cancer.
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 on or after
their most recent line of anticancer therapy.
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.
b. Note: Patients who have platinum-refractory or platinum-resistant disease to
frontline treatment are excluded.
6. Patient must have received at least 1 prior line of systemic anticancer
therapy in the platinum sensitive setting, 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. 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.
b. Adjuvant ± neoadjuvant is considered 1 line of therapy.
c. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered
part of the preceding line of therapy (i.e., not counted independently).
d. Therapy that changed due to toxicity in the absence of progression will be
considered part of the same line (ie, not counted independently).
e. Hormonal therapy will be counted as a separate line of therapy unless it was
given as maintenance therapy.
f. Patients having 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.
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 to undergo a pre-treatment tumor biopsy or provide
qualifying archival tumor tissue. All pretreatment tissue must have been
collected no more than 120 days prior to screening. 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 (i.e., 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 described in the protocol.
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 in Protocol for the definition of WOCBP.)

1. Patient has primary platinum-refractory disease or primary platinum
resistance, defined as disease progression during first-line platinumbased
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 (i.e., borderline or lowgrade serous
tumor).
4. Patient requires fluid drainage (eg, paracentesis, thoracentesis,
pericardiocentesis) of >=500 ml within 6 weeks of 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 antiPD1/PDL1 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
3 days prior to the first dose of study drug(s) requiring systemic therapy.
Antibiotics given for periprocedural 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 as described in
the protocol.
18. Patient has had an active second malignancy within the previous 2 years.
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
as described in the protocol.
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.
26. History of bowel obstruction (including sub-occlusive disease) related to
the underlying ovarian disease, history of abdominal fistula, gastrointestinal
perforation or intra-abdominal abscess, or evidence of recto-sigmoid
involvement or bowel involvement on computed tomography (CT) scan.