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NCT02735239

Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer

Completed Phase 1, PHASE2 Results posted Last updated 22 March 2024
What this trial tests

Phase 1, PHASE2 trial testing Durvalumab in Esophageal Cancer in 73 participants. Completed in 16 June 2022.

Timeline
24 June 2016
Primary endpoint
16 June 2022
16 June 2022

Quick facts

Lead sponsorLudwig Institute for Cancer Research
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment73
Start date24 June 2016
Primary completion16 June 2022
Estimated completion16 June 2022
Sites4 locations across United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

Ludwig Institute for Cancer Research

Who can join

18 and older, any sex, with Esophageal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Subjects Reporting Treatment Emergent Adverse Events (TEAEs) Primary · 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, respec

Treatment-emergent adverse events (TEAEs)
GroupValue95% CI
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)12
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo5
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo21
Cohort C: Operable OC; Durva + Chemo11
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy9
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy15
Dose-limiting toxicities (DLTs) during the entire study
GroupValue95% CI
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)0
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo1
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo2
Cohort C: Operable OC; Durva + Chemo0
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy0
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy0
Discontinued due to a TEAE
GroupValue95% CI
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)0
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo0
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo4
Cohort C: Operable OC; Durva + Chemo0
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy0
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy0
DLTs within the 10-week DLT evaluation period
GroupValue95% CI
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)0
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo0
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo0
Number of Subjects With Best Overall Tumor Response by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) Primary · 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 o

GroupValue95% CI
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)2
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo0
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo0
Cohort C: Operable OC; Durva + Chemo3
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy1
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy2
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)3
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo3
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo10
Cohort C: Operable OC; Durva + Chemo1
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy0
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy0
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)5
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo1
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo4
Cohort C: Operable OC; Durva + Chemo0
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy0
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy0
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)1
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo1
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo5
Cohort C: Operable OC; Durva + Chemo1
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy0
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy1
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) Secondary · 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.

GroupValue95% CI
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)2
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo0
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo0
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)2
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo2
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo7
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)3
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo1
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo4
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)1
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo0
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo1
Median Progression-free Survival (PFS) by the Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method Secondary · 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

GroupValue95% CI
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)8.70.9 – 29.1
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo5.21.4 – NA
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo11.93.9 – 15.6
Cohort C: Operable OC; Durva + Chemo25.46.47 – NA
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy32.032.10 – NA
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy9.59NA – NA
Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method Secondary · 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.

GroupValue95% CI
Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)11.83.1 – NA
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo8.62.7 – NA
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo15.69.3 – 33.5
Cohort C: Operable OC; Durva + ChemoNA18.46 – NA
Cohort C-FLOT: Operable OC, Durva + FLOT ChemotherapyNA8.02 – NA
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)TherapyNA13.14 – NA
One Year Survival Rate in Subjects With Operable OC Secondary · 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.

GroupValue95% CI
Cohort C: Operable OC; Durva + Chemo100NA – NA
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy8943.3 – 98.4
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy86.756.4 – 96.5
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) Secondary · 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.

GroupValue95% CI
Cohort C: Operable OC; Durva + Chemo2
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy1
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy3
Cohort C: Operable OC; Durva + Chemo5
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy3
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy7
Cohort C: Operable OC; Durva + Chemo1
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy2
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy1
Cohort C: Operable OC; Durva + Chemo3
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy0
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy2

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A1: Metastatic/Locally Advanced OC, Durva + Chemotherapy (Chemo)
Serious: 7/12 (58%)
Deaths: 9/12
Cohort A2: Metastatic/Locally Advanced OC, Durva, Treme + Chemo
Serious: 4/5 (80%)
Deaths: 5/5
Cohort B: Metastatic/Locally Advanced OC, Durva, Treme + Chemo
Serious: 12/21 (57%)
Deaths: 16/21
Cohort C: Operable OC; Durva + Chemo
Serious: 7/11 (64%)
Deaths: 5/11
Cohort C-FLOT: Operable OC, Durva + FLOT Chemotherapy
Serious: 6/9 (67%)
Deaths: 2/9
Cohort D/D2: Operable OC, Durva + Neoadjuvant Chemo(Radio)Therapy
Serious: 10/15 (67%)
Deaths: 6/15

Serious adverse events (51 terms)

ReactionSystemCohort A1: Metastatic/Loca…Cohort A2: Metastatic/Loca…Cohort B: Metastatic/Local…Cohort C: Operable OC; Dur…Cohort C-FLOT: Operable OC…Cohort D/D2: Operable OC, …
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DysphagiaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
ColitisGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
HaematemesisGastrointestinal disorders
VomitingGastrointestinal disorders
Mucosal inflammationGeneral disorders
PneumoniaInfections and infestations
InfectionInfections and infestations
DehydrationMetabolism and nutrition disorders
Angina pectorisCardiac disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
OdynophagiaGastrointestinal disorders
NauseaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
EnteritisGastrointestinal disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
CholecystitisHepatobiliary disorders
BacteraemiaInfections and infestations
Lower respiratory tract infectionInfections and infestations
Other adverse events (199 terms — click to expand)

ReactionSystemCohort A1: Metastatic/Loca…Cohort A2: Metastatic/Loca…Cohort B: Metastatic/Local…Cohort C: Operable OC; Dur…Cohort C-FLOT: Operable OC…Cohort D/D2: Operable OC, …
FatigueGeneral disorders
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Lipase increasedInvestigations
Neuropathy peripheralNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
OesophagitisGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
Peripheral sensory neuropathyNervous system disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
DyspepsiaGastrointestinal disorders
DysphagiaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Lower respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Weight decreasedInvestigations
DysgeusiaNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Chest painGeneral disorders
Temperature intoleranceGeneral disorders
Oral candidiasisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Dumping syndromeInjury, poisoning and procedural complications
Amylase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
DysaesthesiaNervous system disorders
ParaesthesiaNervous system disorders
InsomniaPsychiatric disorders
HypothyroidismEndocrine disorders
Vision blurredEye disorders

Most-reported serious reactions: Malignant neoplasm progression, Dysphagia, Anaemia, Colitis, Diarrhoea, Haematemesis, Vomiting, Mucosal inflammation.

Data from ClinicalTrials.gov NCT02735239 adverse events section.

Sponsor's own description

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).

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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Trials by the same sponsor.

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Data sources for this page

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