Esophageal Cancer
Conditions
Keywords
Oesophageal Cancer, Oesophageal adenocarcinoma, Oesophageal squamous cell carcinoma, Immunotherapy, Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), Programmed cell death protein 1 (PD-1), Programmed death ligand 1 (PD-L1)
Brief summary
This is an open-label, Phase 1/2 study to evaluate the safety of durvalumab (MEDI4736) in combination with oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC) and with neoadjuvant chemo(radio)therapy before surgery in operable OC. The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts. The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 and A2) and an expansion Phase 2 (Cohorts B, C, C-FLOT, D/D2).
Detailed description
This is an open-label, Phase 1/2 study to evaluate the safety of immunotherapy in combination with chemo (radio) therapy with the following cohorts: * Cohorts A1, A2, and B: Oxaliplatin/capecitabine chemotherapy in metastatic/locally advanced oesophageal cancer (OC). * Cohort C: Neoadjuvant oxaliplatin/capecitabine chemotherapy before surgery in operable OC. * Cohort C-FLOT: Neoadjuvant 5-fluorouracil (5-FU), leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy before surgery in operable OC. * Cohort D/D2: Neoadjuvant paclitaxel/carboplatin chemotherapy + radiotherapy before surgery in operable OC. The immunotherapy will be given for a 4-week period before starting the standard chemo(radio)therapy, continuing durvalumab treatment once the chemotherapy starts for all cohorts except Cohort D. The study will include 2 phases, a safety run-in Phase 1 (Cohorts A1 and A2) and an expansion Phase 2 (Cohorts B including the higher dose tremelimumab cohort from Cohort A2, C, C-FLOT, and D/D2). Phase 1 will evaluate the safety of durvalumab alone (Cohort A1) administered before chemotherapy (oxaliplatin + capecitabine) in subjects with metastatic or locally advanced OC. After completion of Cohort A1, Phase 2 in Cohorts C, C-FLOT, and D/D2 will begin, and a safety review will determine whether to explore the tremelimumab + durvalumab combination (Cohort A2). Phase 2 includes the expansion into Cohorts B, C, C-FLOT, and D/D2. Once Cohort A1 is cleared, there will be concurrent enrollment into Phase 2 expansion for Cohorts C, C-FLOT and D/D2 (subjects with operable OC with neoadjuvant chemotherapy or chemoradiotherapy before surgery) and the tremelimumab dose-escalation phase for Cohort A2 (37.5 mg and 75 mg). Once Cohort A2 is completed, another safety review will determine the dose of tremelimumab to be included in the recommended combination dose (RCD) to start enrollment into the Cohort B (subjects with metastatic/locally advanced OC) expansion phase. Subjects treated at the RCD in Cohort A2 (tremelimumab 75 mg) will be included in Cohort B. Subjects in Cohorts C, C-FLOT and D/D2 will undergo surgery after completing treatment, and they will be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this is within 3 months of surgery. Subjects in Cohort C-FLOT may receive durvalumab, FLOT, or durvalumab plus FLOT at the discretion of the investigator.
Interventions
DRUGDurvalumab
Anti PD-L1 antibody
DRUGTremelimumab
Anti CTLA-4 antibody
DRUGOxaliplatin
IV administered chemotherapy
DRUGCapecitabine
orally-administered chemotherapy
RADIATIONRadiotherapy
DRUGPaclitaxel
IV administered chemotherapy
DRUGCarboplatin
IV administered Chemotherapy
DRUG5-fluorouracil (5-FU)
IV administered chemotherapy
DRUGLeucovorin
chemo-protective agent
DRUGDocetaxel
IV administered chemotherapy
Sponsors
AstraZeneca
Ludwig Institute for Cancer Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histological diagnosis of oesophageal or gastrooesophageal cancer and have not received prior chemotherapy. * Cohorts A and B - metastatic/locally advanced cancer * Cohorts C/C-FLOT and D/D2 - deemed suitable for surgery with curative intent 2. Anticipated lifespan greater than 4 months. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. At the time of day 1 of the study, subjects with brain metastases must be asymptomatic for at least 4 weeks and: * at least 8 weeks without tumour progression after any whole brain radiotherapy * at least 4 weeks since craniotomy and resection or stereotactic radiosurgery * at least 3 weeks without new brain metastases as evidenced by MRI/CT 5. Adequate normal organ and marrow function. Laboratory parameters for vital functions should be in the normal range. Laboratory abnormalities that are not clinically significant are generally permitted. 6. Written informed consent obtained from the subject; subject been informed of other treatment options, and able to comply with study requirements. 7. Age 18 years or older.
Exclusion criteria
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study. 2. Participation in another clinical study with an investigational product during the last 4 weeks. 3. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction. 4. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis). 5. History of allogeneic organ transplant. 6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C, known immunodeficiency or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. 7. Known history of previous clinical diagnosis of tuberculosis. 8. History of pneumonitis or interstitial lung disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | up to 1 year | Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 110 days after the last dose of study treatment. Treatment-emergent AEs were those that occurred or worsened after administration of the first dose of study treatment. In Cohorts A1, A2 and B, 12, 5 and 7 subjects, respectively, were monitored for dose limiting toxicities (DLTs) during the first 10 weeks of treatment (DLT evaluation period). |
| Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | up to 1 year | Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. In the other cohorts, tumor response was assessed at baseline, post-surgery and 14 days after the last dose. In Cohorts C-FLOT and D, an additional assessment was done prior to surgery and in Cohorts C and D, an additional assessment was done in Cycle 3. Per irRECIST, measurable lesions are categorized as follows: Immune-related Complete Response (irCR): Complete disappearance of all target lesions; Immune-related Partial Response (irPR): ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); Immune-related Progressive Disease (irPD): ≥ 20% increase from nadir in TMTB; Immune-related Stable Disease (irSD): not meeting above criteria; irNon-CR/Non-PD: irNon-CR/Non-PD is preferred over SD when no lesions can be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method | Up to 3 years | After completion of treatment, all subjects were followed for survival every 6 months for up to 3 years from start of treatment. OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive. Per protocol amendment 8.0, all post study follow-up for the collection of survival data was discontinued as of June 30, 2022. |
| Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Up to 23 weeks | Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. Per irRECIST, measurable lesions are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria; irNon-CR/Non-PD: irNon-CR/Non-PD is preferred over SD when no lesions can be measured. |
| Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Up to 7months | 18F- fluorodeoxyglucose (18F-FDG) PET scans were conducted at baseline and in Cycle 3 in Cohorts C and D, and after completion of therapy in Cohort C-FLOT and D2. Complete metabolic response: 18F-FDG-avid lesions revert to background of normal tissues in which they are located; Partial metabolic response: 30% or greater reduction in measurable tumors; Stable Metabolic Response: no visible change in metabolic activity of tumor; Progressive metabolic disease: increase in intensity or extent of tumor metabolic activity or new sites of activity. |
| One Year Survival Rate in Subjects With Operable OC | up to 12 months | OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive. Per protocol amendment 8.0, all post study follow-up for the collection of survival data was discontinued as of June 30, 2022. |
| Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method | Up to 3 years | Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. In the other cohorts, tumor response was assessed at baseline, post-surgery and 14 days after the last dose. In Cohorts C-FLOT and D, an additional assessment was done prior to surgery and in Cohorts C and D, an additional assessment was done in Cycle 3. In Cohorts A1, A2 and B, PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression did not occur. For Cohorts C, C-FLOT and D/D2, PFS is measured from the date of surgery. Per irRECIST, irPD was defined as a ≥ 20% increase from nadir in the TMTB. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) Durvalumab (750 mg IV every two weeks \[Q2W\]) was to be given for up to 11 doses. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Durvalumab: Anti PD-L1 antibody
Oxaliplatin: IV administered chemotherapy
Capecitabine: orally-administered chemotherapy | 12 |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (37.5 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Durvalumab: Anti PD-L1 antibody
Tremelimumab: Anti CTLA-4 antibody
Oxaliplatin: IV administered chemotherapy
Capecitabine: orally-administered chemotherapy | 5 |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo Durvalumab (750 mg IV Q2W) was to be given for up to 11 doses. One dose of tremelimumab (75 mg IV) was given on the same day as the first dose of durvalumab. Oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy was started on the day of the third dose of durvalumab and continued for 6 doses.
Durvalumab: Anti PD-L1 antibody
Tremelimumab: Anti CTLA-4 antibody
Oxaliplatin: IV administered chemotherapy
Capecitabine: orally-administered chemotherapy | 21 |
| Cohort C: Operable OC; Durva + Chemo Durvalumab (750 mg IV Q2W) was to be given for up to 5 doses. Two cycles of neoadjuvant oxaliplatin (130 mg/m\^2 IV)/capecitabine (1250 mg/m\^2/day given orally) chemotherapy were to be administered before surgery. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Durvalumab: Anti PD-L1 antibody
Oxaliplatin: IV administered chemotherapy
Capecitabine: orally-administered chemotherapy | 11 |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy Durvalumab (750 mg IV Q2W) was to be given for up to 6 doses. Two cycles of neoadjuvant 5-fluorouracil (5-FU) (2600 mg/m\^2 24-hr IV), leucovorin (200 mg/m\^2 IV), oxaliplatin (85 mg/m\^2 IV), and docetaxel (50 mg/m\^2 IV) chemotherapy (FLOT) were to be administered before surgery starting on the day of the third dose of durvalumab. Subjects were to undergo surgery 6 to 8 weeks after completing chemotherapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions), FLOT or durvalumab plus FLOT at the discretion of the Investigator once recovered from surgery, provided that this was within 3 months of surgery.
Durvalumab: Anti PD-L1 antibody
5-fluorouracil (5-FU): IV administered chemotherapy
Oxaliplatin: IV administered chemotherapy
Leucovorin: chemo-protective agent
Docetaxel: IV administered chemotherapy | 9 |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy Durvalumab (750 mg IV Q2W) was to be given for 2 doses. This was followed by five weekly doses of neoadjuvant paclitaxel (50 mg/m\^2 IV) / carboplatin (AUC 2) IV chemotherapy + radiotherapy (41.4 Gy radiotherapy given over 23 fractions) before surgery. Subjects could receive an additional dose of durvalumab after completion of chemoradiation.
In Cohort D2, subjects continued durvalumab for 3 additional doses while receiving chemoradiation. Subjects were to undergo surgery 6 to 8 weeks after completing chemo(radio)therapy or according to institutional policies for surgery; and would be eligible to resume durvalumab dosing (to a maximum of 12 infusions) once recovered from surgery, provided that this was within 3 months of surgery.
Durvalumab: Anti PD-L1 antibody
Radiotherapy
Paclitaxel: IV administered chemotherapy
Carboplatin: IV administered chemotherapy | 15 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 4 | 0 | 0 | 0 |
| Overall Study | Death | 1 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Progressive disease | 3 | 1 | 3 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Total | Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Cohort C: Operable OC; Durva + Chemo | Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.5 years | 59 years | 65 years | 56 years | 57 years | 58.0 years | 55.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 70 Participants | 14 Participants | 8 Participants | 11 Participants | 20 Participants | 5 Participants |
| Region of Enrollment United Kingdom | 12 participants | 73 participants | 15 participants | 9 participants | 11 participants | 21 participants | 5 participants |
| Sex: Female, Male Female | 2 Participants | 11 Participants | 3 Participants | 1 Participants | 0 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 10 Participants | 62 Participants | 12 Participants | 8 Participants | 11 Participants | 17 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 12 | 5 / 5 | 16 / 21 | 5 / 11 | 2 / 9 | 6 / 15 |
| other Total, other adverse events | 12 / 12 | 5 / 5 | 21 / 21 | 11 / 11 | 9 / 9 | 15 / 15 |
| serious Total, serious adverse events | 7 / 12 | 4 / 5 | 12 / 21 | 7 / 11 | 6 / 9 | 10 / 15 |
Outcome results
Primary
Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs)
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through 110 days after the last dose of study treatment. Treatment-emergent AEs were those that occurred or worsened after administration of the first dose of study treatment. In Cohorts A1, A2 and B, 12, 5 and 7 subjects, respectively, were monitored for dose limiting toxicities (DLTs) during the first 10 weeks of treatment (DLT evaluation period).
Time frame: up to 1 year
Population: All subjects who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Discontinued due to a TEAE | 0 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | DLTs within the 10-week DLT evaluation period | 0 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Dose-limiting toxicities (DLTs) during the entire study | 0 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Treatment-emergent adverse events (TEAEs) | 12 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Dose-limiting toxicities (DLTs) during the entire study | 1 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Discontinued due to a TEAE | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | DLTs within the 10-week DLT evaluation period | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Treatment-emergent adverse events (TEAEs) | 5 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | DLTs within the 10-week DLT evaluation period | 0 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Treatment-emergent adverse events (TEAEs) | 21 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Dose-limiting toxicities (DLTs) during the entire study | 2 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Discontinued due to a TEAE | 4 Participants |
| Cohort C: Operable OC; Durva + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Discontinued due to a TEAE | 0 Participants |
| Cohort C: Operable OC; Durva + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Dose-limiting toxicities (DLTs) during the entire study | 0 Participants |
| Cohort C: Operable OC; Durva + Chemo | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Treatment-emergent adverse events (TEAEs) | 11 Participants |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Dose-limiting toxicities (DLTs) during the entire study | 0 Participants |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Discontinued due to a TEAE | 0 Participants |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Treatment-emergent adverse events (TEAEs) | 9 Participants |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Treatment-emergent adverse events (TEAEs) | 15 Participants |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Dose-limiting toxicities (DLTs) during the entire study | 0 Participants |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) | Discontinued due to a TEAE | 0 Participants |
Primary
Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. In the other cohorts, tumor response was assessed at baseline, post-surgery and 14 days after the last dose. In Cohorts C-FLOT and D, an additional assessment was done prior to surgery and in Cohorts C and D, an additional assessment was done in Cycle 3. Per irRECIST, measurable lesions are categorized as follows: Immune-related Complete Response (irCR): Complete disappearance of all target lesions; Immune-related Partial Response (irPR): ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); Immune-related Progressive Disease (irPD): ≥ 20% increase from nadir in TMTB; Immune-related Stable Disease (irSD): not meeting above criteria; irNon-CR/Non-PD: irNon-CR/Non-PD is preferred over SD when no lesions can be measured.
Time frame: up to 1 year
Population: All subjects who received at least one dose of study treatment and had a baseline and at least one post-baseline disease assessment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irCR | 2 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPR | 3 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irSD | 5 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPD | 1 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irNon-CR/Non-PD | 0 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Not Evaluable | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPR | 3 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPD | 1 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Not Evaluable | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irCR | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irSD | 1 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irNon-CR/Non-PD | 0 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Not Evaluable | 0 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irNon-CR/Non-PD | 1 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPD | 5 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irSD | 4 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irCR | 0 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPR | 10 Participants |
| Cohort C: Operable OC; Durva + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPD | 1 Participants |
| Cohort C: Operable OC; Durva + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPR | 1 Participants |
| Cohort C: Operable OC; Durva + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irSD | 0 Participants |
| Cohort C: Operable OC; Durva + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Not Evaluable | 3 Participants |
| Cohort C: Operable OC; Durva + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irNon-CR/Non-PD | 1 Participants |
| Cohort C: Operable OC; Durva + Chemo | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irCR | 3 Participants |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irCR | 1 Participants |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irNon-CR/Non-PD | 0 Participants |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPR | 0 Participants |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irSD | 0 Participants |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPD | 0 Participants |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Not Evaluable | 4 Participants |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPD | 1 Participants |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irSD | 0 Participants |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irNon-CR/Non-PD | 0 Participants |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Not Evaluable | 5 Participants |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPR | 0 Participants |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irCR | 2 Participants |
Secondary
Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method
After completion of treatment, all subjects were followed for survival every 6 months for up to 3 years from start of treatment. OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive. Per protocol amendment 8.0, all post study follow-up for the collection of survival data was discontinued as of June 30, 2022.
Time frame: Up to 3 years
Population: All subjects who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method | 11.8 months |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method | 8.6 months |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method | 15.6 months |
| Cohort C: Operable OC; Durva + Chemo | Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method | NA months |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method | NA months |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method | NA months |
Secondary
Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. In the other cohorts, tumor response was assessed at baseline, post-surgery and 14 days after the last dose. In Cohorts C-FLOT and D, an additional assessment was done prior to surgery and in Cohorts C and D, an additional assessment was done in Cycle 3. In Cohorts A1, A2 and B, PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression did not occur. For Cohorts C, C-FLOT and D/D2, PFS is measured from the date of surgery. Per irRECIST, irPD was defined as a ≥ 20% increase from nadir in the TMTB.
Time frame: Up to 3 years
Population: All subjects who received at least one dose of study treatment and had a baseline and at least one post-baseline disease assessment. One subject in Cohort D progressed prior to surgery and as a result was not included in the PFS after surgery assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method | 8.7 months |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method | 5.2 months |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method | 11.9 months |
| Cohort C: Operable OC; Durva + Chemo | Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method | 25.4 months |
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method | 32.03 months |
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy | Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method | 9.59 months |
Secondary
Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), and in Cycles 1, 3, 5 and 6 in Cohorts A1, A2 and B. Per irRECIST, measurable lesions are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria; irNon-CR/Non-PD: irNon-CR/Non-PD is preferred over SD when no lesions can be measured.
Time frame: Up to 23 weeks
Population: All subjects in Cohorts A1, A2 and B who received at least one dose of study treatment and had a baseline and at least one post-baseline disease assessment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irCR | 2 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPR | 2 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irSD | 3 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPD | 1 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irNon-CR/Non-PD | 0 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Not evaluable | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Not evaluable | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irCR | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPD | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irNon-CR/Non-PD | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPR | 2 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irSD | 1 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPR | 7 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irSD | 4 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | Not evaluable | 1 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irPD | 1 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irCR | 0 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Number of Subjects With Metastatic/Locally Advanced Oesophageal Cancer (OC) Who Had a Response at Cycle 6 by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | irNon-CR/Non-PD | 1 Participants |
Secondary
One Year Survival Rate in Subjects With Operable OC
OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive. Per protocol amendment 8.0, all post study follow-up for the collection of survival data was discontinued as of June 30, 2022.
Time frame: up to 12 months
Population: All subjects with Operable OC in Cohorts C, C-FLOT and D/D2 who received at least one dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | One Year Survival Rate in Subjects With Operable OC | 100 percent of participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | One Year Survival Rate in Subjects With Operable OC | 89 percent of participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | One Year Survival Rate in Subjects With Operable OC | 86.7 percent of participants |
Secondary
Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST)
18F- fluorodeoxyglucose (18F-FDG) PET scans were conducted at baseline and in Cycle 3 in Cohorts C and D, and after completion of therapy in Cohort C-FLOT and D2. Complete metabolic response: 18F-FDG-avid lesions revert to background of normal tissues in which they are located; Partial metabolic response: 30% or greater reduction in measurable tumors; Stable Metabolic Response: no visible change in metabolic activity of tumor; Progressive metabolic disease: increase in intensity or extent of tumor metabolic activity or new sites of activity.
Time frame: Up to 7months
Population: All operable OC subjects in Cohorts C, C-FLOT and D/D2 who had a baseline PET scan and a PET scan prior to surgery.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Complete Metabolic Response | 2 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Partial Metabolic Response | 5 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Stable Disease | 1 Participants |
| Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo) | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Progressive Disease | 3 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Progressive Disease | 0 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Complete Metabolic Response | 1 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Stable Disease | 2 Participants |
| Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Partial Metabolic Response | 3 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Progressive Disease | 2 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Partial Metabolic Response | 7 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Stable Disease | 1 Participants |
| Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo | Overall Response Prior to Surgery in Operable OC (Cohorts C, C-FLOT and D/D2) Using Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) | Complete Metabolic Response | 3 Participants |