Fallopian Tube Cancer, Platinum-resistant Ovarian Cancer, Primary Peritoneal Cancer
Conditions
Keywords
PROC, EOC, ALKS 4230, IL-2, Ovarian Cancer, KEYNOTE-C71, Platinum Resistant, Epithelian Ovarian Cancer, Nemvaleukin alfa, Pembrolizumab, ARTISTRY-7, ART-7, paclitaxel, pegylated liposoma doxorubicin, PLD, topotecan, gemzar, gemcitabine
Brief summary
This is a Phase 3, multicenter, open-label, randomized study of nemvaleukin in combination with pembrolizumab versus protocol-specific Investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Detailed description
Patients 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: Nemvaleukin monotherapy Arm 4: Investigator's choice chemotherapy include one of the following: pegylated liposomal doxorubicin (PLD), paclitaxel, topotecan, or gemcitabine.
Interventions
BIOLOGICALNemvaleukin and Pembrolizumab Combination
Nemvaleukin: 6 µg/kg/day; Days 1 through 5 of 21-day cycles; IV infusion over 30 minutes and Pembrolizumab: 200 mg; Day 1 of 21-day cycles; IV infusion over 30 minutes
BIOLOGICALPembrolizumab
Pembrolizumab: 200 mg; Day 1 of 21-day cycles; IV infusion over 30 minutes
BIOLOGICALNemvaleukin
Nemvaleukin: 6 µg/kg/day; Days 1 through 5 of 21-day cycles; IV infusion over 30 minutes
DRUGPegylated Liposomal Doxorubicin (PLD)
40 mg/m2; Day 1 of 28-day cycles; IV infusion; 1 mg/min (Cycle 1); 60 min infusion (Cycles 2+)
DRUGPaclitaxel
80 mg/m2; Days 1, 8, 15, and 22 of 28-day cycles; IV infusion over 60 min
DRUGTopotecan
4 mg/m2; Days 1, 8, and 15 of 28-day cycles; or 1.25 mg/m2, Days 1 through 5 of 21-day cycles; IV infusion over 30 min
DRUGGemcitabine
1,000 mg/m2; Days 1 and 8 of 21-day cycles; IV infusion over 30 min
Sponsors
Merck Sharp & Dohme LLC
Mural Oncology, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is female and ≥18 years of age. * Patient has histologically confirmed diagnosis of EOC (ie, high-grade serous, endometrioid of any grade, clear cell), fallopian tube cancer, or primary peritoneal cancer. * 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. * 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. * Patient has at least one measurable lesion that qualifies as a target lesion based on RECISTv1.1. * Patient is willing to undergo a pre-treatment tumor biopsy or provide qualifying archival tumor tissue.
Exclusion criteria
* 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). * Patient has histologically confirmed diagnosis of EOC with mucinous or carcinosarcoma subtype. * Patient has nonepithelial tumor (eg, germline or stromal cell tumor) or ovarian tumor with low malignant potential (ie, borderline or low-grade serous tumor). * Patient requires fluid drainage (eg, paracentesis, thoracentesis, pericardiocentesis) of ≥500 mL within 4 weeks of first dose of study drug. * 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. * Patient has prior exposure to any anti-PD1/PD-L1 therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From the first dose of study drug up to 24 months | Estimates based on Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) as Assessed by Investigator | From the first dose of study drug up to 20 months | Response is based on RECIST v1.1 criteria. |
| Duration of Response (DOR) as Assessed by Investigator | From the first dose of study drug up to 20 months | Response is based on RECIST v1.1 criteria. |
| Time to Response (TTR) as Assessed by Investigator | From the first dose of study drug up to 20 months | Response is based on RECIST v1.1 criteria. |
| Objective Response Rate (ORR) as Assessed by Investigator | From the first dose of study drug up to 20 months | Response is based on RECIST v1.1 criteria. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to 90 days after last dose (up to 23 months) | — |
| Progression-free Survival (PFS) as Assessed by Investigator | From the first dose of study drug up to 20 months | — |
| Percentage of Participants With Cancer Antigen (CA)-125 Response as Defined by the Gynecologic Cancer Inter Group (GCIG) | From the first dose of study drug up to 20 months | A Cancer Antigen-125 response is defined as at least a 50% reduction in CA-125 levels from baseline, and the response must be confirmed and maintained for at least 28 days as per the GCIG. |
Countries
Australia, Austria, Belgium, Canada, Czechia, France, Germany, Italy, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted globally from 10 Jan 2022 to 08 May 2025.
Pre-assignment details
Participants with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer were enrolled into 1 of 4 arms to receive nemvaleukin alfa (ALKS 4230) either as monotherapy or in combination with pembrolizumab or in investigator's choice chemotherapy. Study was terminated due to business and strategic decision.
Participants by arm
| Arm | Count |
|---|---|
| Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg Participants received Nemvaleukin 6 mcg/kg/day IV infusion over 30 minutes on Days 1 through 5 of 21-day cycles and Pembrolizumab 200 mg IV infusion over 30 minutes on Day 1 of 21-day cycles. | 184 |
| Pembrolizumab 200 mg Participants received Pembrolizumab 200 mg IV infusion over 30 minutes on Day 1 of 21-day cycles. | 27 |
| Nemvaleukin 6 mcg/kg Participants received Nemvaleukin 6 mcg/kg/day IV infusion over 30 minutes on Days 1 through 5 of 21-day cycles. | 55 |
| Investigator's Choice Chemotherapy Investigator's choice chemotherapy includes one of the following: pegylated liposomal doxorubicin (PLD), paclitaxel, topotecan, or gemcitabine. The Investigator pre-selected the Investigator's choice treatment before the randomization of each participant.
Pegylated Liposomal Doxorubicin (PLD): 40 mg/m\^2; Day 1 of 28-day cycles; IV infusion; 1 mg/min (Cycle 1); 60 min infusion (Cycles 2+).
Paclitaxel: 80 mg/m\^2; Days 1, 8, 15, and 22 of 28-day cycles; IV infusion over 60 min.
Topotecan: 4 mg/m\^2; Days 1, 8, and 15 of 28-day cycles; or 1.25 mg/m2, Days 1 through 5 of 21-day cycles; IV infusion over 30 min.
Gemcitabine: 1,000 mg/m\^2; Days 1 and 8 of 21-day cycles; IV infusion over 30 min. | 190 |
| Total | 456 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 97 | 14 | 31 | 101 |
| Overall Study | Lost to Follow-up | 1 | 2 | 2 | 2 |
| Overall Study | Study terminated by sponsor | 65 | 7 | 13 | 61 |
| Overall Study | Withdrawal by Subject | 21 | 4 | 9 | 26 |
Baseline characteristics
| Characteristic | Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg | Pembrolizumab 200 mg | Nemvaleukin 6 mcg/kg | Investigator's Choice Chemotherapy | Total |
|---|---|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 8.83 | 61.6 years STANDARD_DEVIATION 12.97 | 61.5 years STANDARD_DEVIATION 9.17 | 61.3 years STANDARD_DEVIATION 9.99 | 61.8 years STANDARD_DEVIATION 9.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 0 Participants | 2 Participants | 11 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 165 Participants | 27 Participants | 52 Participants | 175 Participants | 419 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 0 Participants | 1 Participants | 4 Participants | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 42 Participants | 5 Participants | 3 Participants | 33 Participants | 83 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 24 Participants | 1 Participants | 1 Participants | 13 Participants | 39 Participants |
| Race (NIH/OMB) White | 113 Participants | 20 Participants | 51 Participants | 142 Participants | 326 Participants |
| Sex: Female, Male Female | 184 Participants | 27 Participants | 55 Participants | 190 Participants | 456 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 104 / 184 | 15 / 27 | 34 / 55 | 105 / 190 |
| other Total, other adverse events | 177 / 184 | 23 / 27 | 51 / 55 | 171 / 190 |
| serious Total, serious adverse events | 74 / 184 | 8 / 27 | 17 / 55 | 51 / 190 |
Outcome results
Primary
Overall Survival (OS)
Estimates based on Kaplan-Meier method.
Time frame: From the first dose of study drug up to 24 months
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg | Overall Survival (OS) | 10.1 months |
| Pembrolizumab 200 mg | Overall Survival (OS) | 10.1 months |
| Nemvaleukin 6 mcg/kg | Overall Survival (OS) | 10.7 months |
| Investigator's Choice Chemotherapy | Overall Survival (OS) | 9.8 months |
Secondary
Disease Control Rate (DCR) as Assessed by Investigator
Response is based on RECIST v1.1 criteria.
Time frame: From the first dose of study drug up to 20 months
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg | Disease Control Rate (DCR) as Assessed by Investigator | 34.2 percentage of participants |
| Pembrolizumab 200 mg | Disease Control Rate (DCR) as Assessed by Investigator | 25.9 percentage of participants |
| Nemvaleukin 6 mcg/kg | Disease Control Rate (DCR) as Assessed by Investigator | 36.4 percentage of participants |
| Investigator's Choice Chemotherapy | Disease Control Rate (DCR) as Assessed by Investigator | 52.1 percentage of participants |
Secondary
Duration of Response (DOR) as Assessed by Investigator
Response is based on RECIST v1.1 criteria.
Time frame: From the first dose of study drug up to 20 months
Population: ITT population. Here N refers to number of participants with response and were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg | Duration of Response (DOR) as Assessed by Investigator | 5.9 months |
| Investigator's Choice Chemotherapy | Duration of Response (DOR) as Assessed by Investigator | 5.4 months |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug up to 90 days after last dose (up to 23 months)
Population: Safety Set population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 177 Participants |
| Pembrolizumab 200 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 23 Participants |
| Nemvaleukin 6 mcg/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 51 Participants |
| Investigator's Choice Chemotherapy | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 171 Participants |
Secondary
Objective Response Rate (ORR) as Assessed by Investigator
Response is based on RECIST v1.1 criteria.
Time frame: From the first dose of study drug up to 20 months
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg | Objective Response Rate (ORR) as Assessed by Investigator | 9.2 percentage of participants |
| Pembrolizumab 200 mg | Objective Response Rate (ORR) as Assessed by Investigator | 0.0 percentage of participants |
| Nemvaleukin 6 mcg/kg | Objective Response Rate (ORR) as Assessed by Investigator | 0.0 percentage of participants |
| Investigator's Choice Chemotherapy | Objective Response Rate (ORR) as Assessed by Investigator | 11.1 percentage of participants |
Secondary
Percentage of Participants With Cancer Antigen (CA)-125 Response as Defined by the Gynecologic Cancer Inter Group (GCIG)
A Cancer Antigen-125 response is defined as at least a 50% reduction in CA-125 levels from baseline, and the response must be confirmed and maintained for at least 28 days as per the GCIG.
Time frame: From the first dose of study drug up to 20 months
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg | Percentage of Participants With Cancer Antigen (CA)-125 Response as Defined by the Gynecologic Cancer Inter Group (GCIG) | 4.3 percentage of participants |
| Pembrolizumab 200 mg | Percentage of Participants With Cancer Antigen (CA)-125 Response as Defined by the Gynecologic Cancer Inter Group (GCIG) | 0.0 percentage of participants |
| Nemvaleukin 6 mcg/kg | Percentage of Participants With Cancer Antigen (CA)-125 Response as Defined by the Gynecologic Cancer Inter Group (GCIG) | 0.0 percentage of participants |
| Investigator's Choice Chemotherapy | Percentage of Participants With Cancer Antigen (CA)-125 Response as Defined by the Gynecologic Cancer Inter Group (GCIG) | 13.2 percentage of participants |
Secondary
Progression-free Survival (PFS) as Assessed by Investigator
Time frame: From the first dose of study drug up to 20 months
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg | Progression-free Survival (PFS) as Assessed by Investigator | 1.5 months |
| Pembrolizumab 200 mg | Progression-free Survival (PFS) as Assessed by Investigator | 1.5 months |
| Nemvaleukin 6 mcg/kg | Progression-free Survival (PFS) as Assessed by Investigator | 1.5 months |
| Investigator's Choice Chemotherapy | Progression-free Survival (PFS) as Assessed by Investigator | 2.9 months |
Secondary
Time to Response (TTR) as Assessed by Investigator
Response is based on RECIST v1.1 criteria.
Time frame: From the first dose of study drug up to 20 months
Population: ITT population. Here N refers to number of participants with response and were analyzed for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nemvaleukin 6 mcg/kg and Pembrolizumab 200 mg | Time to Response (TTR) as Assessed by Investigator | 2.83 months |
| Investigator's Choice Chemotherapy | Time to Response (TTR) as Assessed by Investigator | 1.64 months |