Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Rare Diseases

Recurrence

Adenocarcinoma

Esophageal Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Durvalumab

Immunoglobulins

Tremelimumab

Interferon-gamma

Antineoplastic Agents, Immunological

Immunologic Factors

Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma will receive intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).

Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).

Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma will receive IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature will receive IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, participants will receive MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

MEDI4736 will be administered by IV infusion in combination with tremelimumab.

MEDI4736 + tremelimumab

MEDI4736 will be administered by IV infusion.

MEDI4736

Tremelimumab will be administered by IV infusion.

MEDI4736+tremelimumab

MedImmune, LLC MedImmune, LLC

This is a randomized, multicenter, open-label, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, PK, pharmacodynamics, and immunogenicity of MEDI4736 in combination with tremelimumab, MEDI4736 monotherapy or tremelimumab monotherapy in participants with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma.

A Phase 1b/2 Study of MEDI4736 With Tremelimumab, MEDI4736 or Tremelimumab Monotherapy in Gastric or GEJ Adenocarcinoma

A Phase 1b/2 Study of MEDI4736 in Combination With Tremelimumab, MEDI4736 Monotherapy, and Tremelimumab Monotherapy in Subjects With Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

A DLT was defined as any Grade 3 or higher toxicity that occurs during the DLT evaluation period (From first dose of Study drug \[Day 1\] through 28 days after the administration of MEDI4736 and tremelimumab). The DLTs are: any Grade 4 immune-related adverse event (irAE), any Grade \>=3 non-irAE, \>= Grade 3 colitis, Grade 3 or 4 noninfectious pneumonitis irrespective of duration, Grade 2 pneumonitis, liver transaminase elevation \> 8 × upper limit of normal (ULN) or total bilirubin \> 5 × ULN. Immune-related AEs are defined as AEs of an immune nature (ie, inflammatory) in the absence of a clear alternative etiology.

Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urine.

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal findings in the vital signs parameters (temperature, blood pressure \[BP\], pulse rate \[or pulse oximetry at screening\], and respiratory rate). Abnormal physical examinations are defined as any abnormal impact on measurements of height and weight.

Number of participants with abnormal electrocardiograms (ECGs) reported as TEAEs are reported. Abnormal ECGs are defined as any abnormal findings in heart rate, PR, RR, QRS and QT intervals from the primary lead of the digital 12-lead ECG.

The ECOG scale of performance status describes the level of functioning of participants in terms of their ability to care for themselves, daily activity, and physical ability. ECOG Performance Status Scorings are: 0= fully active, able to carry on all pre-disease performance without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (for example, light house work, office work); 2= ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5= dead. The baseline performance status of participants is presented.

OR: best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per RECIST v1.1. BOR: best response (CR, PR, stable disease \[SD\], progressive disease \[PD\], and not evaluable) among all overall responses recorded from date of randomization for Arm A, B, C participants or date of first dose of study drug for Arms D, E participants until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy.

The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS-6.

OR: best overall response (BOR) of confirmed complete response (CR) or partial response (PR) per RECIST v1.1. BOR: best response (CR, PR, stable disease \[SD\], progressive disease \[PD\], and not evaluable) among all overall responses recorded from date of randomization of participants or date of first dose of study drug until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy.

The DSD was defined as the time from the date of first dose of study treatment for Phase 1b until the first date of documented PD (per RECIST v1.1), or death due to any cause, whichever occurred first. PD is at least a 20% increase in sum of diameters of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method was used to evaluate DSD.

Best percentage change from baseline of the SLD of target lesions per RECIST v1.1 was derived as the biggest decease or the smallest increase from baseline on the SLD among all post-baseline disease assessment including unscheduled assessments. Best percent change is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction.

The disease control rate at 16 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 110 days, following the date of first dose of study drug. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.

The disease control rate at 24 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 166 days, following the date of first dose of study drug. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.

The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Phase 1b participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS.

The disease control rate at 16 weeks was defined as the percentage of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 110 days, following the date of randomization for Arm A, B, and C participants and the date of first dose of study drug for Arm D and E participants. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.

The disease control rate at 24 weeks was defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or had SD with duration of SD for a minimum duration of 166 days, following the date of randomization for Arm A, B, and C participants and the date of first dose of study drug for Arm D and E participants. The DC was defined as a BOR of confirmed CR, confirmed PR or SD per RECIST v1.1. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study.

The DoR was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression according to RECIST v1.1 that occurred subsequently after response or death due to any cause, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline. Kaplan Meier method was used to evaluate DoR.

TTR: time from date of randomization of participants for Arm A, B, and C or date of first dose of study drug for Arm D and Arm E until first documented OR per RECIST v1.1. OR: BOR of confirmed CR or PR per RECIST v1.1. BOR: best response (CR, PR, SD, PD, and not evaluable) among all overall responses recorded from date of randomization/date of first dose of study drug until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in SOD of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD; PD: at least 20% increase in SOD of target lesions from smallest sum (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method used to evaluate TTR.

The DSD was defined as the time from the date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until the first date of documented PD (per RECIST v1.1), or death due to any cause, whichever occurred first. PD is at least a 20% increase in sum of diameters of target lesions from smallest sum on study (at least 5 mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy. Kaplan Meier method was used to evaluate DSD.

The PFS was defined as the time from the date of randomization for Arm A, B, and C participants or the date of first dose of study treatment for Arm D and E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS.

The PFS-9 is the 9-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 9 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, C participants or the date of first dose of study drug for Arm D and E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS.

The OS was defined as the time from date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until death due to any cause. OS was censored at last known alive date. Kaplan Meier method was used to evaluate OS. Kaplan Meier method was used to evaluate OS.

The OS was defined as the time from date of randomization for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants until 12 months. OS was censored at last known alive date. Kaplan Meier method was used to evaluate OS. Kaplan Meier method was used to evaluate OS and 95% confidence interval.

Percentage of participants with OR with positive IFN-γ gene expression is reported. OR: BOR of confirmed CR or PR per RECIST v1.1. BOR: best response (CR, PR, SD, PD, and not evaluable) among all overall responses recorded from date of randomization for Arm A, B, C participants or date of first dose of study drug for Arms D, E participants until progression, or last evaluable disease assessment or discontinuation from the study, whichever occurred first. CR: disappearance of all target/non-target lesions; PR: at least 30% decrease in sum of diameters (SOD) of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD from smallest SOD on study; PD: at least 20% increase in SOD of target lesions from smallest sum on study (at least 5mm), appearance of one or more new lesions, substantial worsening in non-target disease, increase in tumor burden leading to discontinuation of therapy.

Percentage of participants with PFS at 6 month with positive IFN-γ gene expression is reported. The PFS-6 is the 6-month progression-free survival rate, which was the percentage of participants who were progression free and alive at 6 months. PFS was defined as the time from the date of first dose of study drug for Arm A, B, and C participants or the date of first dose of study drug for Arm D and Arm E participants to the earlier of the dates of the first objective documentation of radiographic disease progression (per RECIST v1.1) or death due to any cause. PFS was censored at the date of their last evaluable tumor assessment. Kaplan Meier method was used to evaluate PFS-6.

Percentage of participants with objective response in Phase 2 by programmed death-ligand (PD-L1) status is reported. PD-L1 is a protein that may be found on some normal cells and in higher-than-normal amounts on some types of cancer cells. It plays a role in regulating the immune response against some types of cancers and therefore, is the target for some anticancer drugs. PD-L1 status was based on the percentage of tumor cells from baseline tumor tissue samples with PD-L1 membrane staining: PD-L1 high if \>= 1% tumor cells (better response), PD-L1 low/neg if \< 1% tumor cells (low response).

MedImmune LLC

Participants in second-line therapy with gastric or gastroesophageal junction (GEJ) adenocarcinoma received intravenous (IV) infusion of 20 mg/kg MEDI4736 every 4 weeks (Q4W) for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Phase 1b-M20 mg/kg (Q4W) + T 1 mg/kg (Q4W) Fw M10 mg/kg (Q2W)

Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Phase 2 Arm A-(M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)

Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg MEDI4736 Q2W for 12 months (up to 26 doses).

Phase 2 Arm B-M10 mg/kg (Q2W)

Participants in second-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 10 mg/kg tremelimumab Q4W for 7 doses and then Q12W for 2 doses for 12 months (for a total of up to 9 doses).

Phase 2 Arm C-T10 mg/kg (Q4W)

Participants in third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Phase 2 Arm D-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)

Participants in second and third-line therapy with metastatic or recurrent gastric or GEJ adenocarcinoma and a positive IFN-γ gene expression signature received IV infusion of 20 mg/kg MEDI4736 Q4W for 4 months (up to 4 doses) in combination with IV 1 mg/kg tremelimumab Q4W for 4 months (up to 4 doses in total). Thereafter, MEDI4736 monotherapy (10 mg/kg) every 2 weeks (Q2W) to complete a total of 12 months of therapy (up to 18 additional doses).

Phase 2 Arm E-M20 mg/kg (Q4W) + T1 mg/kg Fw M10 mg/kg (Q2W)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.

Shahram Rahimian

TEAEs

TESAEs

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 1b

Dose limiting toxicity (DLT) evaluable population included all participants in the Phase 1b who received the Study drug and completed safety follow-up through the DLT evaluation period or experience a DLT during the DLT evaluation period (From first dose of Study drug \[Day 1\] through 28 days after the administration of MEDI4736 and tremelimumab).

Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1b

Anaemia

Lymphopenia

Haemoglobin decreased

Prothrombin time prolonged

Activated partial thromboplastin time prolonged

Blood alkaline phosphatase increased

Blood bilirubin increased

Gamma-glutamyltransferase increased

Transaminases increased

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 1b

Pyrexia

Weight decreased

Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 1b

Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 1b

ECOG 0

ECOG 1

Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 1b

Percentage of Participants With Objective Response (OR) in Phase 2

Progression Free Survival at 6 (PFS-6) Month in Phase 2

Percentage of Participants With Objective Response in Phase 1b

As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. DSD was analyzed for participants with SD.

Duration of Stable Disease (DSD) in Phase 1b

Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 1b

Percentage of Participants With Disease Control at 16 Weeks in Phase 1b

Percentage of Participants With Disease Control at 24 Weeks in Phase 1b

Progression Free Survival at 6 Month in Phase 1b

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Phase 2

Lymphocyte count decreased

White blood cell count decreased

International normalised ratio increased

Platelet count decreased

Blood fibrinogen decreased

Hepatic function abnormal

Alanine aminotransferase increased

Aspartate aminotransferase increased

Hyperthyroidism

Hypothyroidism

Blood thyroid stimulating hormone increased

Thyroxine free decreased

Tri-iodothyronine free decreased

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Phase 2

Atrial fibrillation

Bradycardia

Hypertension

Hypotension

Hypoxia

Respiratory distress

Sinus tachycardia

Tachycardia

Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Phase 2

Angina pectoris

Ventricular tachycardia

Cardiac failure congestive

Atrial tachycardia

Pericardial effusion

Cardiac failure

Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Phase 2

Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline in Phase 2

Percentage of Participants With Disease Control at 16 Weeks in Phase 2

Percentage of Participants With Disease Control at 24 Weeks in Phase 2

As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Participants with OR were analyzed for the specified outcome measure.

Duration of Response (DoR) in Phase 2

Time to Response (TTR) in Phase 2

Duration of Stable Disease in Phase 2

As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Participants with any reduction in tumor size were analyzed for the specified outcome measure.

Median Best Percentage Change From Baseline of the Sum of Longest Diameters (SLD) of Target Lesions in Phase 2

Progression Free Survival in Phase 2

Progression Free Survival at 9 Month (PFS-9) in Phase 2

Overall Survival (OS) in Phase 2

Overall Survival at 12 Months in Phase 2

Percentage of Participants With Objective Response With Positive Interferon Gamma (IFN-γ) Gene Expression in Phase 2

As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. Only those participants were analyzed who were at risk at 6 months.

Percentage of Participants With Progression Free Survival (PFS) at 6 Month With Positive IFN-γ Gene Expression in Phase 2

PD-L1 high

PD-L1 low/negative

Percentage of Participants With Objective Response in Phase 2 by Programmed Death-ligand (PD-L1) Status

Overall Study

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

MEDI4736 + tremelimumab combination therapy

MEDI4736 + Tremelimumab combination therapy

MEDI4736 + Tremelimumab

Standard of Care

Nassim Morsli, MD

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.

The main objectives of the study are to:

* assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in patients with squamous cell carcinoma of the head and neck (SCCHN), in terms of overall survival (OS), regardless of PDL-1 status
* assess the efficacy of MEDI4736 monotherapy versus SOC in patients with SCCHN, in terms of OS, regardless of PDL-1 status

Patients will undergo a screening assessment on their tumor tissue sample to determine PD-L1 expression per a pre-specified cut-off level. Patients with ≥25% of tumor cells with membrane staining will be considered PD-L1 positive while those with 0% to 24% of tumor cells with membrane staining will be considered PD-L1 negative. Based on the underlying PD-L1 status, patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 monotherapy, MEDI4736 + tremelimumab combination therapy, or SoC therapy. Patients who discontinue treatment in 1 treatment group may not switch to treatment in a different group.

Stratification factors include PD-L1 status, human papillomavirus status, (in patients with oropharyngeal cancer only), and smoking status.

Tumor assessments will be performed every 8 weeks until objective tumor response by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer

A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy and MEDI4736 in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

OS is defined as the time from the date of randomization until death due to any cause. OS was analyzed for the full analysis set, regardless of programmed death-ligand 1 (PD-L1) status.

OS is defined as the time from the date of randomization until death due to any cause. PD-L1 negative was defined as \<25% of tumor cells with membrane staining for PD-L1 at any intensity.

OS is defined as the time from the date of randomization until death due to any cause. PD-L1 positive was defined as ≥25% of tumor cells with membrane staining for PD-L1 at any intensity.

PFS was defined as the time from the date of randomization until the date of objective disease progression or death based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

The percentage of participants who experienced an objective response (complete response \[CR\] or partial response \[PR\]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.

Median DoR, in months, based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A complete response was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A partial response was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.

6 Months: The percentage of participants who had a best objective response of complete response (CR) or partial response (PR) in the first 6 months or had demonstrated stable disease (SD) for a minimum interval of 24 weeks following randomization.

12 Months: The percentage of participants who had a best objective response of CR or PR within 12 months or had demonstrated SD for a minimum interval of 48 weeks following randomization.

Objective response was based on investigator assessments, according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.

APF is defined as the percentage of participants who are alive and progression free at 6 months and 12 months after randomization. Estimates of progression free survival were based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). Objective disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Percentage of participants alive at 12, 18 and 24 months using a Kaplan Meier estimate.

Number of participants with confirmed objective disease progression (PD) at the time of the participant's last evaluable response evaluation criteria in solid tumors 1.1 (RECIST1.1) assessment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD-L1 negative was defined as \<25% of tumor cells with membrane staining for PD-L1 at any intensity.

The percentage of PD-L1 negative participants who experienced an objective response (complete response \[CR\] or partial response \[PR\]), based on investigator assessments according to response evaluation criteria in solid tumors 1.1 (RECIST1.1). A CR was defined as the disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. A PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. PD-L1 negative was defined as \<25% of tumor cells with membrane staining for PD-L1 at any intensity.

The EORTC QLQ-C30 consists of 30 questions that can be combined to produce functional scales (e.g. physical), symptom scales (e.g. fatigue), and a global measure of health status. Each of the scales are measured from 0 to 100. Deterioration was defined as a 10-point decrease from baseline in a functioning or global health status/ quality of life score or a 10-point increase from baseline in a symptom score.

The EORTC QLQ-H\&N35 comprises of 35 questions to assess head and neck cancer symptoms (e.g. pain, swallowing). Deterioration was defined as a 10-point increase from baseline in the symptom score.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Inclusive of AEs and serious AEs.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1b/2 Study of MEDI4736 With Tremelimumab, MEDI4736 or Tremelimumab Monotherapy in Gastric or GEJ Adenocarcinoma	NCT02340975	Gastric or Gast...	MEDI4736 + trem... MEDI4736 + trem... MEDI4736 Tremelimumab MEDI4736+tremel... MEDI4736 + trem...	18 Years - 99 Years	MedImmune LLC
Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer	NCT02369874	Recurrent or Me...	MEDI4736 MEDI4736 + Trem... Standard of Car...	18 Years - 96 Years	AstraZeneca
A Phase 1b/2 Study of MEDI4736 With Tremelimumab, MEDI4736 or Tremelimumab Monotherapy in Gastric or GEJ Adenocarcinoma	NCT02340975	Gastric or Gast...	MEDI4736 + trem... MEDI4736 + trem... MEDI4736 Tremelimumab MEDI4736+tremel... MEDI4736 + trem...	18 Years - 99 Years	MedImmune LLC

Spots Global Cancer Trial Database for medi4736 + tremelimumab