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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-005298-19 | EudraCT Number | ||
| ESR 15-10891 | Other Identifier | AstraZeneca reference number |
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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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).
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A1: Metastatic/locally advanced OC, Durva + Chemotherapy (Chemo) | Experimental | 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. |
|
| Cohort A2: Metastatic/locally advanced OC, Durva, Treme + Chemo | Experimental | 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. |
|
| Cohort B: Metastatic/locally advanced OC, Durva, Treme + Chemo | Experimental | 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. |
|
| Cohort C: Operable OC; Durva + Chemo | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Durvalumab | Drug | Anti PD-L1 antibody |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | up to 1 year |
| 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. | up to 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Histological diagnosis of oesophageal or gastrooesophageal cancer and have not received prior chemotherapy.
Anticipated lifespan greater than 4 months.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
At the time of day 1 of the study, subjects with brain metastases must be asymptomatic for at least 4 weeks and:
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.
Written informed consent obtained from the subject; subject been informed of other treatment options, and able to comply with study requirements.
Age 18 years or older.
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Mark Middleton | University of Oxford, UK | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Facility | Dundee | DD1 9SY | United Kingdom | |||
| Research Facility |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Bohnsack O, Hoos A, Ludajic K. Adaptation of the immune related response criteria: irRECIST. Ann Oncol. 2014 Sep;25(suppl 4):iv361-iv72 [Abstract 4958]. doi: 10.1093/annonc/mdu342.23. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 11, 2022 |
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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.
|
| Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy | Experimental | 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. |
|
| Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(radio)therapy | Experimental | 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. |
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| Tremelimumab | Drug | Anti CTLA-4 antibody |
|
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| Oxaliplatin | Drug | IV administered chemotherapy |
|
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| Capecitabine | Drug | orally-administered chemotherapy |
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| Radiotherapy | Radiation |
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| Paclitaxel | Drug | IV administered chemotherapy |
|
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| Carboplatin | Drug | IV administered Chemotherapy |
|
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| 5-fluorouracil (5-FU) | Drug | IV administered chemotherapy |
|
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| Leucovorin | Drug | chemo-protective agent |
|
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| Docetaxel | Drug | IV administered chemotherapy |
|
|
| Up to 23 weeks |
| 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. | Up to 3 years |
| 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. | Up to 3 years |
| 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. | up to 12 months |
| 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. | Up to 7months |
| Nottingham |
| NG5 1PB |
| United Kingdom |
| Research Facility | Oxford | OX3 9DU | United Kingdom |
| Research Facility | Southampton | SO16 6YD | United Kingdom |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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 |
| FG005 | 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 |
|
| COMPLETED | All subjects who completed protocol specified treatment. For Cohorts C and D/D2 this includes subjects who completed pre-surgery treatment. |
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| NOT COMPLETED |
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|
All subjects who received at least one dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | 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 |
| BG005 | 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 |
| BG006 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | All subjects who received at least one dose of study treatment. | Posted | Count of Participants | Participants | up to 1 year |
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| 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. | All subjects who received at least one dose of study treatment and had a baseline and at least one post-baseline disease assessment. | Posted | Count of Participants | Participants | up to 1 year |
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| 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. | 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. | Posted | Count of Participants | Participants | Up to 23 weeks |
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| 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. | 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. | Posted | Median | 95% Confidence Interval | months | Up to 3 years |
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| 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. | All subjects who received at least one dose of study treatment. | Posted | Median | 95% Confidence Interval | months | Up to 3 years |
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| 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. | All subjects with Operable OC in Cohorts C, C-FLOT and D/D2 who received at least one dose of study treatment. | Posted | Number | 95% Confidence Interval | percent of participants | up to 12 months |
| |||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Count of Participants | Participants | Up to 7months |
|
All AEs occurring between the signing of informed consent and the off-study date (i.e., through 110 days after the last dose of study treatment, up 18 months) were documented, regardless of a causal relationship to study drug. AEs that occur or worsen in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). All cause mortality included all deaths which were reported up to 3 years.
AE documentation included onset/resolution dates, severity using NCI CTCAE (version 4.03), seriousness, relationship to study drug, study drug action taken, treatment and outcome. Preferred terms were counted once per subject at the maximum reported grade.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 9 | 12 | 7 | 12 | 12 | 12 |
| EG001 | 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 | 5 | 4 | 5 | 5 | 5 |
| EG002 | 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 | 16 | 21 | 12 | 21 | 21 | 21 |
| EG003 | 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 | 5 | 11 | 7 | 11 | 11 | 11 |
| EG004 | 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 | 2 | 9 | 6 | 9 | 9 | 9 |
| EG005 | 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 | 6 | 15 | 10 | 15 | 15 | 15 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Orchitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Herpes simplex | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Liver abscess | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Neutropenic sepsis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.1) | Systematic Assessment |
| |
| Encephalitis autoimmune | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Postoperative wound complication | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
| |
| Electrolyte imbalance | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Oesophagectomy | Surgical and medical procedures | MedDRA (18.1) | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Jejunostomy refashioning | Surgical and medical procedures | MedDRA (18.1) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Blepharospasm | Eye disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal distention | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Epigastric discomfort | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Eructation | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Lip pruritus | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Malabsorption | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Oesophageal ulcer | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Retching | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Oesophageal fistula | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Sensitivity of teeth | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Steatorrhoea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Tongue coated | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Early satiety | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Feeling cold | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Infusion site reaction | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Temperature intolerance | General disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Balanitis candida | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Nail infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Medical device site infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Oesophageal candidiasis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Vulvovaginal candidiasis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
| |
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
| |
| Wound complication | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
| |
| Dumping syndrome | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
| |
| Postoperative wound complication | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
| |
| Wound haemorrhage | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Blood thyroid stimulating hormone decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Blood iron decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Blood magnesium decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Jaw disorder | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Myopathy | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.1) | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.1) | Systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dysaesthesia | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dizziness postural | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Encephalitis autoimmune | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Muscle contractions involuntary | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Head discomfort | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Poor quality sleep | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Laryngospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dermatitis psoriasiform | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pruritus generalized | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Pigmentation disorder | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Systemic lupus erythematosus rash | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
| |
| Oropharyngeal candidiasis | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan Skipper | Ludwig Institute for Cancer Research | 212-450-1539 | jskipper@lcr.org |
| Aug 16, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D004938 | Esophageal Neoplasms |
| C562730 | Adenocarcinoma Of Esophagus |
| D000077277 | Esophageal Squamous Cell Carcinoma |
| C563326 | Diabetes Mellitus, Insulin-Dependent, 12 |
| C565324 | Parkinson Disease 4, Autosomal Dominant Lewy Body |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D018307 | Neoplasms, Squamous Cell |
Not provided
Not provided
| ID | Term |
|---|---|
| C000613593 | durvalumab |
| C520704 | tremelimumab |
| D000077150 | Oxaliplatin |
| D000069287 | Capecitabine |
| D011878 | Radiotherapy |
| D011827 | Radiation |
| D017239 | Paclitaxel |
| D016190 | Carboplatin |
| D005472 | Fluorouracil |
| D002955 | Leucovorin |
| D000077143 | Docetaxel |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D013812 | Therapeutics |
| D055585 | Physical Phenomena |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Dose-limiting toxicities (DLTs) during the entire study |
|
|
| Discontinued due to a TEAE |
|
|
| DLTs within the 10-week DLT evaluation period |
|
|
| OG001 | 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 |
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
|
|
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 |
| OG002 | 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 |
|
|
| OG001 | 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 |
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
|
|
| OG002 | 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 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
|
|
| OG002 | 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 |
|
|
| 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 |
| OG002 | 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 |
|
|