Fallopian tube cancer Ovarian cancer Peritoneal cancer
Conditions
Interventions
Subjects will be centrally allocated in a randomized fashion (3:1:1:3) to
receive either:
• Arm 1: nemvaleukin and pembrolizumab combination therapy
• Arm 2: pembrolizumab monotherapy
• Arm 3: nemval
Sponsors
Alkermes Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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]).<b
Exclusion criteria
Exclusion criteria: 1. Patient has primary platinum-refractory disease or primary platinum resistance, defined as disease progression during first-line platinumbased therapy (refractory) or disease progression =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 =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 a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: • Progression-free survival (PFS) as assessed by Investigator, based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Key Secondary Endpoints: • Objective response rate (ORR) as assessed by Investigator, based on RECIST v1.1 Other Secondary Endpoints: • Overall Survival (OS) • Disease control rate (DCR), duration of response (DOR), and time to response (TTR) as assessed by Investigator, based on RECIST v1.1 • Cancer antigen (CA)-125 response as defined by the Gynecologic Cancer InterGroup (GCIG) • Safety as assessed by treatment-emergent adverse events (TEAEs), clinical laboratory parameters, vital signs, and electrocardiograms (ECGs) | — |
Countries
Netherlands
Outcome results
None listed