High-grade Serous Ovarian Carcinoma, Ovarian Carcinoma
Conditions
Brief summary
The primary objective is to evaluate in participants with high-grade serous ovarian cancer (HGSOC), whether the reduction from baseline in circulating tumor deoxyribonucleic acid (ctDNA) at Cycle 3 (ΔctDNA) is larger in participants receiving MK-4830 + pembrolizumab in combination with standard of care (SOC) therapy than in those receiving pembrolizumab + SOC therapy.
Interventions
BIOLOGICALPembrolizumab
200 mg by IV infusion on Day 1 of each 21-day cycle
DRUGPaclitaxel
175 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle
DRUGCarboplatin
AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle
BIOLOGICALAvastin
According to local practice and at the choice of the investigator.
BIOLOGICALMK-4830
800 mg by IV infusion on Day 1 of each 21-day cycle
DRUGDocetaxel
75 mg/m\^2 by IV infusion on Day 1 of each 21-day cycle
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Has histologically-confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV HGSOC, primary peritoneal cancer, or fallopian tube cancer. * Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant and adjuvant setting. * Is a candidate for interval debulking surgery. * Is able to provide archival tissue or newly obtained core, incisional, or excisional biopsy of a tumor lesion. * Has adequate organ functions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA) | Baseline and Week 7 | Blood samples were collected to determine levels of ctDNA. The fold change in the mean mutant/tumor molecules per mL (MTM/mL) at Cycle 3 from baseline is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Association of Change From Baseline in ctDNA With pCR | Baseline and Week 12 | Blood samples were collected to determine levels of ctDNA. pCR was defined as all surgical specimens collected during the interval debulking surgery microscopically negative for residual tumor. pCR rate was defined as percentage of participants with pCR. Per protocol, the association of change from baseline in ctDNA with pCR in participants with surgery and pCR was reported. |
| Participants With Surgery and Chemotherapy Response Score (CRS): Change From Baseline in ctDNA | Baseline and Week 12 | Blood samples were collected to determine levels of ctDNA. CRS is a 3-tiered scoring system (CRS1-3) based on the pathological analysis of surgically removed omental masses. CRS was defined as CRS1 (minimal or no tumor response, mainly viable tumor), CRS2 (appreciable tumor response amidst viable tumor that is readily identifiable and regularly distributed), and CRS3 (complete or near-complete response, characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size); higher values indicate greater response. Per protocol, change from baseline in ctDNA in participants with surgery and CRS was reported. |
| Association of Change From Baseline in ctDNA With CRS3 | Baseline and Week 12 | Blood samples were collected to determine levels of ctDNA. CRS is a 3-tiered scoring system (CRS1-3) based on the pathological analysis of surgically removed omental masses. CRS was defined as CRS1 (minimal or no tumor response, mainly viable tumor), CRS2 (appreciable tumor response amidst viable tumor that is readily identifiable and regularly distributed), and CRS3 (complete or near-complete response, characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size); higher values indicate greater response. CRS3 rate was defined as percentage of participants with CRS3. Per protocol, the association of change from baseline in ctDNA with CRS3 in participants with surgery and CRS was reported. |
| Participants With Surgery and Pathological Complete Response (pCR): Change From Baseline in ctDNA | Baseline and Week 12 | Blood samples were collected to determine levels of ctDNA. pCR was defined as all surgical specimens collected during the interval debulking surgery microscopically negative for residual tumor. Per protocol, change from baseline in ctDNA in participants with surgery and pCR was reported. |
| CRS3 Rate | Up to approximately 12 weeks | CRS is a 3-tiered scoring system (CRS1-3) based on the pathological analysis of surgically removed omental masses. CRS was defined as CRS1 (minimal or no tumor response, mainly viable tumor), CRS2 (appreciable tumor response amidst viable tumor that is readily identifiable and regularly distributed), and CRS3 (complete or near-complete response, characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size); higher values indicate greater response. CRS3 rate was defined as percentage of participants with CRS3. Per protocol, CRS3 rate as assessed by local pathologist was reported. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 26 months | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). The number of participants who experienced one or more AEs was reported. |
| Number of Participants Who Discontinued Study Intervention Due to an AE | Up to approximately 28 weeks | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). The number of participants who discontinued study intervention due to an AE was reported. |
| pCR Rate | Up to approximately 12 weeks | pCR rate was defined as the percentage of participants with all surgical specimens collected during the interval debulking surgery that were microscopically negative for residual tumor. The pCR rate as assessed by local pathologist was reported. |
Countries
Belgium, Canada, Chile, Israel, Italy, Poland, Singapore, South Korea, Spain, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 Before surgery participants received pembrolizumab, paclitaxel (or docetaxel), carboplatin, and MK-4830 by intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks \[Q3W\]) for 3 cycles. After surgery participants received pembrolizumab, paclitaxel (or docetaxel), and carboplatin (with avastin \[or biosimilar\] at the investigator's discretion and per institutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. | 80 |
| Pembrolizumab + SOC Before surgery participants received pembrolizumab, paclitaxel (or docetaxel), and carboplatin by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. After surgery participants received pembrolizumab, paclitaxel (or docetaxel), and carboplatin (with avastin \[or biosimilar\] at the investigator's discretion and per institutional guidelines) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. | 80 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 5 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 52 | 53 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Pembrolizumab + Standard of Care (SOC) + MK-4830 | Pembrolizumab + SOC | Total |
|---|---|---|---|
| Age, Continuous | 60.1 Years STANDARD_DEVIATION 9.5 | 61.5 Years STANDARD_DEVIATION 10.2 | 60.8 Years STANDARD_DEVIATION 9.9 |
| Detectable Baseline Circulating Tumor Deoxyribonucleic Acid (ctDNA) | 214.4 MTM/mL STANDARD_DEVIATION 421.9 | 233.9 MTM/mL STANDARD_DEVIATION 393.2 | 224.5 MTM/mL STANDARD_DEVIATION 405.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 10 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants | 68 Participants | 131 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 24 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 66 Participants | 54 Participants | 120 Participants |
| Sex: Female, Male Female | 80 Participants | 80 Participants | 160 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 80 | 5 / 80 |
| other Total, other adverse events | 75 / 79 | 79 / 80 |
| serious Total, serious adverse events | 28 / 79 | 33 / 80 |
Outcome results
Primary
Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA)
Blood samples were collected to determine levels of ctDNA. The fold change in the mean mutant/tumor molecules per mL (MTM/mL) at Cycle 3 from baseline is presented.
Time frame: Baseline and Week 7
Population: All randomized participants who received at least one dose of study intervention, had detectable ctDNA at baseline, and had assessed ctDNA at Cycle 3.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 | Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA) | 0.08 Fold change | Standard Deviation 0.24 |
| Pembrolizumab + SOC | Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA) | 0.04 Fold change | Standard Deviation 0.1 |
Secondary
Association of Change From Baseline in ctDNA With CRS3
Blood samples were collected to determine levels of ctDNA. CRS is a 3-tiered scoring system (CRS1-3) based on the pathological analysis of surgically removed omental masses. CRS was defined as CRS1 (minimal or no tumor response, mainly viable tumor), CRS2 (appreciable tumor response amidst viable tumor that is readily identifiable and regularly distributed), and CRS3 (complete or near-complete response, characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size); higher values indicate greater response. CRS3 rate was defined as percentage of participants with CRS3. Per protocol, the association of change from baseline in ctDNA with CRS3 in participants with surgery and CRS was reported.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least one dose of study intervention, had surgery, and had CRS and ctDNA data available for assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 | Association of Change From Baseline in ctDNA With CRS3 | 45.7 Percentage of Participants |
| Pembrolizumab + SOC | Association of Change From Baseline in ctDNA With CRS3 | 23.1 Percentage of Participants |
Secondary
Association of Change From Baseline in ctDNA With pCR
Blood samples were collected to determine levels of ctDNA. pCR was defined as all surgical specimens collected during the interval debulking surgery microscopically negative for residual tumor. pCR rate was defined as percentage of participants with pCR. Per protocol, the association of change from baseline in ctDNA with pCR in participants with surgery and pCR was reported.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least one dose of study intervention, had surgery, and had pCR and ctDNA data available for assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 | Association of Change From Baseline in ctDNA With pCR | 12.8 Percentage of Participants |
| Pembrolizumab + SOC | Association of Change From Baseline in ctDNA With pCR | 11.3 Percentage of Participants |
Secondary
CRS3 Rate
CRS is a 3-tiered scoring system (CRS1-3) based on the pathological analysis of surgically removed omental masses. CRS was defined as CRS1 (minimal or no tumor response, mainly viable tumor), CRS2 (appreciable tumor response amidst viable tumor that is readily identifiable and regularly distributed), and CRS3 (complete or near-complete response, characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size); higher values indicate greater response. CRS3 rate was defined as percentage of participants with CRS3. Per protocol, CRS3 rate as assessed by local pathologist was reported.
Time frame: Up to approximately 12 weeks
Population: All randomized participants who received at least one dose of study intervention, received surgery, and had CRS data available for assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 | CRS3 Rate | 43.6 Percentage of Participants |
| Pembrolizumab + SOC | CRS3 Rate | 23.0 Percentage of Participants |
95% CI: [3.5, 37]
Secondary
Number of Participants Who Discontinued Study Intervention Due to an AE
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). The number of participants who discontinued study intervention due to an AE was reported.
Time frame: Up to approximately 28 weeks
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 | Number of Participants Who Discontinued Study Intervention Due to an AE | 13 Participants |
| Pembrolizumab + SOC | Number of Participants Who Discontinued Study Intervention Due to an AE | 15 Participants |
Secondary
Number of Participants Who Experienced an Adverse Event (AE)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). The number of participants who experienced one or more AEs was reported.
Time frame: Up to approximately 26 months
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 | Number of Participants Who Experienced an Adverse Event (AE) | 77 Participants |
| Pembrolizumab + SOC | Number of Participants Who Experienced an Adverse Event (AE) | 80 Participants |
Secondary
Participants With Surgery and Chemotherapy Response Score (CRS): Change From Baseline in ctDNA
Blood samples were collected to determine levels of ctDNA. CRS is a 3-tiered scoring system (CRS1-3) based on the pathological analysis of surgically removed omental masses. CRS was defined as CRS1 (minimal or no tumor response, mainly viable tumor), CRS2 (appreciable tumor response amidst viable tumor that is readily identifiable and regularly distributed), and CRS3 (complete or near-complete response, characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size); higher values indicate greater response. Per protocol, change from baseline in ctDNA in participants with surgery and CRS was reported.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least one dose of study intervention, had surgery, and had CRS and ctDNA data available for assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 | Participants With Surgery and Chemotherapy Response Score (CRS): Change From Baseline in ctDNA | 0.09 Fold Change | Standard Deviation 0.28 |
| Pembrolizumab + SOC | Participants With Surgery and Chemotherapy Response Score (CRS): Change From Baseline in ctDNA | 0.04 Fold Change | Standard Deviation 0.1 |
Secondary
Participants With Surgery and Pathological Complete Response (pCR): Change From Baseline in ctDNA
Blood samples were collected to determine levels of ctDNA. pCR was defined as all surgical specimens collected during the interval debulking surgery microscopically negative for residual tumor. Per protocol, change from baseline in ctDNA in participants with surgery and pCR was reported.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least one dose of study intervention, had surgery, and had pCR and ctDNA data available for assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 | Participants With Surgery and Pathological Complete Response (pCR): Change From Baseline in ctDNA | 0.05 Fold Change | Standard Deviation 0.13 |
| Pembrolizumab + SOC | Participants With Surgery and Pathological Complete Response (pCR): Change From Baseline in ctDNA | 0.04 Fold Change | Standard Deviation 0.1 |
Secondary
pCR Rate
pCR rate was defined as the percentage of participants with all surgical specimens collected during the interval debulking surgery that were microscopically negative for residual tumor. The pCR rate as assessed by local pathologist was reported.
Time frame: Up to approximately 12 weeks
Population: All randomized participants who received at least one dose of study intervention, received surgery, and had pCR data available for assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + Standard of Care (SOC) + MK-4830 | pCR Rate | 10.3 Percentage of Participants |
| Pembrolizumab + SOC | pCR Rate | 9.2 Percentage of Participants |
95% CI: [-10, 12.9]