Durvalumab and Tremelimumab in Treating Patients With Rec... | NCT03373760

ID	Type	Description	Link
NCI-2016-01597	Registry Identifier	CTRP (Clinical Trial Reporting Program)
S1400F
S1400F	Other Identifier	SWOG
S1400F	Other Identifier	CTEP
U10CA180888	U.S. NIH Grant/Contract		View source

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the objective response rate (confirmed and unconfirmed, complete and partial) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 among patients treated with durvalumab (MEDI4736) plus tremelimumab.

SECONDARY OBJECTIVES:

I. To estimate the duration of response (DoR) among patients who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by RECIST 1.1.

II. To estimate the duration of response (DoR) per immune-related response criteria among patients who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by RECIST 1.1.

III. To evaluate overall survival (OS) among patients treated with durvalumab (MEDI4736) plus tremelimumab.

IV. To evaluate investigator-assessed progression-free survival (IA-PFS) among patients treated with durvalumab (MEDI4736) plus tremelimumab.

V. To evaluate IA-PFS assessed by immune-related response criteria (irRC-IA-PFS) among patients treated with durvalumab (MEDI4736) plus tremelimumab.

VI. To evaluate the frequency and severity of toxicities associated with durvalumab (MEDI4736) plus tremelimumab.

TERTIARY OBJECTIVES:

I. To explore the association of potential predictive markers identified in S1400A, with response and progression-free survival (PFS).

II. To explore the association of PD-L1 expression status with response and PFS.

III. To contribute to an ongoing serum and tumor bank in S1400.

OUTLINE:

Patients receive tremelimumab intravenously (IV) over 60 minutes on day 1 for courses 1-4 and durvalumab IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years, and then at the end of year 3.

Label	Type	Description	Intervention Names
Treatment (tremelimumab, durvalumab)	Experimental	Patients receive tremelimumab IV over 60 minutes on day 1 for courses 1-4 and durvalumab IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: Durvalumab Other: Laboratory Biomarker Analysis Biological: Tremelimumab

Name	Type	Description	Arm Group Labels	Other Names
Durvalumab	Biological	Given IV	Treatment (tremelimumab, durvalumab)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Objective Response Rate	Percentage of participants with confirmed or unconfirmed, complete or partial response to treatment with MEDI4736 (durvalumab) plus tremelimumab per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Complete Response (CR): Complete disappearance of all target and non-target lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to < 1.0 cm. All disease must be assessed using the same technique as baseline. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline.	From date of registration to progression or treatment discontinuation, up to 2 years and 5.5 months.

Secondary Outcomes

Measure	Description	Time Frame
Duration of Response (DoR) Among Patients Who Achieve a Complete Response (CR) or Partial Response (PR) (Confirmed and Unconfirmed) by RECIST 1.1.	Time from date of first documentation of response (CR or PR) to date of first documentation of progression assessed by local review or symptomatic deterioration, or death from any cause among patients who achieve a response. Patients last known to be alive without report of progression are censored at date of last disease assessment. For patients with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan will be used as the date of progression. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed and an absolute increase of at least 0.5 cm; Unequivocal progression of non-measurable disease in the opinion of the treating physician (explanation must be provided); Appearance of any new lesion/site; Death due to disease without prior documentation of progression and without symptomatic deterioration

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients must have been assigned to S1400F
Patients must have progressed during or after prior platinum-based chemotherapy; patients whose only prior platinum-based chemotherapy regimen was for stage I-III disease (i.e. patient has not received any platinum-based chemotherapy for stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy; patients must have experienced disease progression during or after prior anti-PD-1 or anti-PD-L1 antibody monotherapy as their most recent line of treatment; prior PD-1/PD-L1 combination therapy is not permitted
Prior exposure to CTLA-4 inhibitors (ipilimumab and tremelimumab) is not permitted; prior exposure to the following is allowed: attenuated vaccines, anti-EGFR agents, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
Patients must not have received nitrosoureas or mitomycin-C within 42 days prior to sub-study registration
Patients must not have any prior documented autoimmune or inflammatory disease (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome) within 3 years prior to sub-study registration; patients with vitiligo, immune-mediated alopecia, Grave?s disease, or psoriasis requiring systemic treatment within the past 2 years are not eligible; patients with hypothyroidism (e.g. post Hashimoto syndrome) who are stable on hormone replacement therapy are eligible
Patients must not have any history of primary immunodeficiency
Patients must not have received any immunosuppressive medication within 28 days prior to sub-study registration and must not be planning to receive these medications while on protocol therapy; systemic corticosteroids must be stopped at least 24 hours prior to sub-study registration; however, intranasal and inhaled corticosteroids are allowed at any time before and during protocol therapy
Patients must not have experienced a grade 3 or worse immune-related adverse event (irAE) (except asymptomatic nonbullous/nonexfoliative rash) or any unresolved irAE grade 2, nor have experienced a toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1 immunotherapy
Patients must not have any history of organ transplant that requires use of immunosuppressives
Patients must not have any known allergy or reaction to any component of the durvalumab (MEDI4736) and/or tremelimumab formulation
Patients must not have clinical signs or symptoms of active tuberculosis infection
Patients must not have received a live attenuated vaccination within 28 days prior to sub-study registration
Patients must not have known human immunodeficiency virus (HIV), or a known positive test for hepatitis B virus surface antigen (HBV sAg), or hepatitis C virus ribonucleic acid (HCV antibody) indicating current acute or chronic infection; patients with a positive hepatitis C antibody with a negative viral load are allowed
Patients must have a thyroid-stimulating hormone (TSH) with reflex free T3/free T4 (if TSH is out of normal range) and electrocardiogram (EKG) obtained within 7 days prior to sub-study registration
Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens

Name	Affiliation	Role
Vassiliki Papadimitrakopoulou	SWOG Cancer Research Network	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham Cancer Center		Birmingham	Alabama	35233	United States
Anchorage Associates in Radiation Medicine

PubMed Identifier	Type	Citation	Retractions
34429332	Derived	Leighl NB, Redman MW, Rizvi N, Hirsch FR, Mack PC, Schwartz LH, Wade JL, Irvin WJ, Reddy SC, Crawford J, Bradley JD, Stinchcombe TE, Ramalingam SS, Miao J, Minichiello K, Herbst RS, Papadimitrakopoulou VA, Kelly K, Gandara DR. Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760). J Immunother Cancer. 2021 Aug;9(8):e002973. doi: 10.1136/jitc-2021-002973.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Treatment (Tremelimumab, Durvalumab)	Patients receive tremelimumab IV over 60 minutes on day 1 for courses 1-4 and durvalumab IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Durvalumab: Given IV Laboratory Biomarker Analysis: Correlative studies Tremelimumab: Given IV

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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	Oct 21, 2019

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00067.6(49.7 to 89.8) BG00167.8(46.6 to 84.0) BG00267.7(46.6 to 89.8)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00010 BG00112 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Race : White

Title	Measurements
	BG00024 BG00126 BG002

Number of prior lines of therapy for stage IV disease

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<2	BG0009 BG00112 BG002

Progression-free survival on prior anti-PD- ( L)1 therapy

Median

Full Range

months

Title

Denominators

Categories

Title	Measurements
	BG0003.0(1.4 to 5.5) BG00110.0(5.6 to 30.4) BG002

Best response to prior anti-PD- ( L)1 therapy

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Complete response	BG0000 BG0013 BG002

Performance status

Participants were graded according to the Zubrod Performance Status Scale. 0 - Fully active, able to carry out 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, e.g. light housework, office work.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
0	BG0007 BG001

Smoking status

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Current smoker	BG00010 BG00110 BG002

Weight loss ≥10% in the 6 months prior to baseline

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG0002 BG0012 BG002

PD-L1 expression (TPS (%))

PD-L1 expression was assessed by immunohistochemistry on tumor samples using 22C3 pharmDx assay (Agilent Technologies, Santa Clara, California, USA).

PD-L1: programmed death ligand 1, TPS: Tumor Proportion Score.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<1%	BG00010 BG001

Tumor mutational burden

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<10 mt/Mb	BG0008 BG00111 BG002

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

Objective Response Rate

Percentage of participants with confirmed or unconfirmed, complete or partial response to treatment with MEDI4736 (durvalumab) plus tremelimumab per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).

Complete Response (CR): Complete disappearance of all target and non-target lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to < 1.0 cm. All disease must be assessed using the same technique as baseline.

Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline.

Eligible and evaluable participants

Posted

Number

95% Confidence Interval

percentage of participants

From date of registration to progression or treatment discontinuation, up to 2 years and 5.5 months.

ID	Title	Description
OG000	Primary PD-(L)1 Resistance Cohort	Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.
OG001	Acquired PD-(L)1 Resistance Cohort	Prior response to immune checkpoint inhibitor monotherapy included 24 weeks or more of disease control (complete response, partial response, or stable disease) after initiation of single agent anti-PD-1/PD-L1 therapy that had subsequently progressed after 24 weeks.

Units	Counts
Participants	OG00028 OG00130

Title

Denominators

Categories

Title	Measurements
	OG0007(0 to 17) OG0010(NA to NA)There were 0 responses in the acquired resistance cohort so 95% confidence interval is not applicable here.

Secondary

Duration of Response (DoR) Among Patients Who Achieve a Complete Response (CR) or Partial Response (PR) (Confirmed and Unconfirmed) by RECIST 1.1.

Time from date of first documentation of response (CR or PR) to date of first documentation of progression assessed by local review or symptomatic deterioration, or death from any cause among patients who achieve a response. Patients last known to be alive without report of progression are censored at date of last disease assessment. For patients with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan will be used as the date of progression.

Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed and an absolute increase of at least 0.5 cm; Unequivocal progression of non-measurable disease in the opinion of the treating physician (explanation must be provided); Appearance of any new lesion/site; Death due to disease without prior documentation of progression and without symptomatic deterioration

Eligible and evaluable participants.

Posted

Number

months

From date of registration to maximum of 2 years and 5.5 months or death.

ID	Title	Description
OG000	Treatment (Tremelimumab, Durvalumab)	Patients receive tremelimumab IV over 60 minutes on day 1 for courses 1-4 and durvalumab IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Durvalumab: Given IV Laboratory Biomarker Analysis: Correlative studies Tremelimumab: Given IV

Secondary

Duration of Response (DoR) Per Immune-related Response Criteria Among Patients Who Achieve a Complete Response (CR) or Partial Response (PR) (Confirmed and Unconfirmed) by RECIST 1.1

Time from date of first documentation of response (CR or PR) to date of first documentation of irRC-progression assessed by local review or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of irRC-progression are censored at date of last disease assessment. For patients with a missing scan (or consecutive missing scans) whose subsequent scan(s) determine irRC-progression, the date of irRCprogression will be the expected date of the first missing scan (as defined by the disease assessment schedule) or the date of the first scan documenting potential irRC-progression, whichever is earliest.

Data were not collected for this outcome.

Posted

From date of registration to maximum of 2 years and 5.5 months or death

ID	Title	Description
OG000	Treatment (Tremelimumab, Durvalumab)	Patients receive tremelimumab IV over 60 minutes on day 1 for courses 1-4 and durvalumab IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Durvalumab: Given IV Laboratory Biomarker Analysis: Correlative studies Tremelimumab: Given IV

Units	Counts
Participants

Secondary

Overall Survival (OS) Among Patients Treated With MEDI4736 (Durvalumab) Plus Tremelimumab

Time from date of sub-study registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Eligible and evaluable participants

Posted

Median

95% Confidence Interval

months

Date of registration to maximum of 2 years and 5.5 months or death.

ID	Title	Description
OG000	Primary PD-(L)1 Resistance Cohort	Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.
OG001	Acquired PD-(L)1 Resistance Cohort	Prior response to immune checkpoint inhibitor monotherapy included 24 weeks or more of disease control (complete response, partial response, or stable disease) after initiation of single agent anti-PD-1/PD-L1 therapy that had subsequently progressed after 24 weeks.

Units	Counts
Participants

Secondary

Investigator-assessed Progression-free Survival (IA-PFS) Among Patients Treated With MEDI4736 (Durvalumab) Plus Tremelimumab.

Time from date of sub-study registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last disease assessment. For patients with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan (as defined by the disease assessment schedule) was used as the date of progression.

Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed and an absolute increase of at least 0.5 cm; Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided); Appearance of any new lesion/site; Death due to disease without prior documentation of progression and without symptomatic deterioration.

Eligible and evaluable participants

Posted

Median

95% Confidence Interval

months

From date of registration to maximum 2 years and 5.5 months or death.

ID	Title	Description
OG000	Primary PD-(L)1 Resistance Cohort	Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.
OG001	Acquired PD-(L)1 Resistance Cohort

Secondary

Investigator-assessed Progression-free Survival (IA-PFS) Assessed by Immune-related Response Criteria (irRC-IA-PFS) Among Patients Treated With MEDI4736 (Durvalumab) Plus Tremelimumab

irRC-progression is defined by progression per RECIST 1.1 except that progression determined by appearance of new lesions or by a 20% increase in the sum of diameters must be confirmed by a second consecutive determination of progression at least 28 days from the date of initial documentation of progression.

Data were not collected for this outcome.

Posted

Date of registration to maximum of 2 years and 5.5 months or death

ID	Title	Description
OG000	Treatment (Tremelimumab, Durvalumab)	Patients receive tremelimumab IV over 60 minutes on day 1 for courses 1-4 and durvalumab IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Durvalumab: Given IV Laboratory Biomarker Analysis: Correlative studies Tremelimumab: Given IV

Secondary

Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Only adverse events that are possibly, probably or definitely related to study drug are reported. CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for reporting serious adverse events (SAEs).

Participants who received at least one dose of protocol treatment

Posted

Number

Participants

Duration of treatment and follow up until death or 2 years and 5.5 months post registration

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	Participants receive tremelimumab and durvalumab on day 1 of each 28-day cycle for four cycles. Starting at cycle 5, participants receive durvalumab on day 1 of each cycle until disease progression or unacceptable toxicity. Tremelimumab: Given IV Durvalumab: Given IV

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 affected58 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 affected58 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0001 affected58 at risk
Atrial flutter	Cardiac disorders	Systematic Assessment	EG0001 affected58 at risk
Cardiac arrest	Cardiac disorders	Systematic Assessment	EG0001 affected58 at risk
Heart failure	Cardiac disorders	Systematic Assessment	EG0001 affected58 at risk
Colitis	Gastrointestinal disorders	Systematic Assessment	EG0002 affected58 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0009 affected58 at risk
Esophageal obstruction	Gastrointestinal disorders	Systematic Assessment	EG0001 affected58 at risk
Esophagitis	Gastrointestinal disorders	Systematic Assessment	EG0001 affected58 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0002 affected58 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0003 affected58 at risk
Chills	General disorders	Systematic Assessment	EG0001 affected58 at risk
Death NOS	General disorders	Systematic Assessment	EG0003 affected58 at risk
Fatigue	General disorders	Systematic Assessment	EG0001 affected58 at risk
Lung infection	Infections and infestations	Systematic Assessment	EG0004 affected58 at risk
Skin infection	Infections and infestations	Systematic Assessment	EG0001 affected58 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected58 at risk
Hip fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected58 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0002 affected58 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0002 affected58 at risk
Blood bilirubin increased	Investigations	Systematic Assessment	EG0001 affected58 at risk
Creatinine increased	Investigations	Systematic Assessment	EG0003 affected58 at risk
Electrocardiogram QT corrected interval prolonged	Investigations	Systematic Assessment	EG0001 affected58 at risk
Fibrinogen decreased	Investigations	Systematic Assessment	EG0001 affected58 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG0002 affected58 at risk
Neutrophil count decreased	Investigations	Systematic Assessment	EG0001 affected58 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0002 affected58 at risk
Serum amylase increased	Investigations	Systematic Assessment	EG0001 affected58 at risk
White blood cell decreased	Investigations	Systematic Assessment	EG0001 affected58 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG0003 affected58 at risk
Dehydration	Metabolism and nutrition disorders	Systematic Assessment	EG0003 affected58 at risk
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected58 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected58 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected58 at risk
Neoplasms benign, malignant and unspecified - Other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0005 affected58 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0002 affected58 at risk
Encephalopathy	Nervous system disorders	Systematic Assessment	EG0001 affected58 at risk
Peripheral sensory neuropathy	Nervous system disorders	Systematic Assessment	EG0002 affected58 at risk
Syncope	Nervous system disorders	Systematic Assessment	EG0001 affected58 at risk
Confusion	Psychiatric disorders	Systematic Assessment	EG0001 affected58 at risk
Hematuria	Renal and urinary disorders	Systematic Assessment	EG0001 affected58 at risk
Bronchopulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected58 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected58 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0007 affected58 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 affected58 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected58 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 affected58 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected58 at risk
Resp, thoracic and mediastinal disorders - Other	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected58 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected58 at risk
Bullous dermatitis	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected58 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 affected58 at risk
Skin and subcutaneous tissue disorders - Other	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected58 at risk
Hematoma	Vascular disorders	Systematic Assessment	EG0001 affected58 at risk
Thromboembolic event	Vascular disorders	Systematic Assessment	EG0001 affected58 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG00024 affected58 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0003 affected58 at risk
Endocrine disorders-Other	Endocrine disorders	Systematic Assessment	EG0003 affected58 at risk
Hypothyroidism	Endocrine disorders	Systematic Assessment	EG0005 affected58 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0005 affected58 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0007 affected58 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG00012 affected58 at risk
Dysphagia	Gastrointestinal disorders	Systematic Assessment	EG0005 affected58 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00016 affected58 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG00010 affected58 at risk
Chills	General disorders	Systematic Assessment	EG0006 affected58 at risk
Edema limbs	General disorders	Systematic Assessment	EG0004 affected58 at risk
Fatigue	General disorders	Systematic Assessment	EG00024 affected58 at risk
Fever	General disorders	Systematic Assessment	EG0005 affected58 at risk
Non-cardiac chest pain	General disorders	Systematic Assessment	EG0004 affected58 at risk
Pain	General disorders	Systematic Assessment	EG0007 affected58 at risk
Bronchial infection	Infections and infestations	Systematic Assessment	EG0003 affected58 at risk
Infections and infestations-Other	Infections and infestations	Systematic Assessment	EG0003 affected58 at risk
Lung infection	Infections and infestations	Systematic Assessment	EG0003 affected58 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0004 affected58 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0005 affected58 at risk
Alkaline phosphatase increased	Investigations	Systematic Assessment	EG0009 affected58 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0006 affected58 at risk
Creatinine increased	Investigations	Systematic Assessment	EG0007 affected58 at risk
Investigations-Other	Investigations	Systematic Assessment	EG0006 affected58 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG00015 affected58 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0004 affected58 at risk
Weight loss	Investigations	Systematic Assessment	EG00013 affected58 at risk
White blood cell decreased	Investigations	Systematic Assessment	EG0003 affected58 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG00016 affected58 at risk
Dehydration	Metabolism and nutrition disorders	Systematic Assessment	EG0007 affected58 at risk
Hypercalcemia	Metabolism and nutrition disorders	Systematic Assessment	EG0008 affected58 at risk
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG00012 affected58 at risk
Hyperkalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0004 affected58 at risk
Hypernatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0004 affected58 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	Systematic Assessment	EG00020 affected58 at risk
Hypocalcemia	Metabolism and nutrition disorders	Systematic Assessment	EG0004 affected58 at risk
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG00012 affected58 at risk
Hypomagnesemia	Metabolism and nutrition disorders	Systematic Assessment	EG0007 affected58 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG00018 affected58 at risk
Hypophosphatemia	Metabolism and nutrition disorders	Systematic Assessment	EG0003 affected58 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0003 affected58 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0004 affected58 at risk
Bone pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0004 affected58 at risk
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0007 affected58 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0004 affected58 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0005 affected58 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0003 affected58 at risk
Dysgeusia	Nervous system disorders	Systematic Assessment	EG0004 affected58 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0004 affected58 at risk
Peripheral sensory neuropathy	Nervous system disorders	Systematic Assessment	EG0004 affected58 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0003 affected58 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0003 affected58 at risk
Insomnia	Psychiatric disorders	Systematic Assessment	EG0004 affected58 at risk
Urinary incontinence	Renal and urinary disorders	Systematic Assessment	EG0003 affected58 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00014 affected58 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00025 affected58 at risk
Hoarseness	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 affected58 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 affected58 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0004 affected58 at risk
Resp, thoracic and mediastinal disorders - Other	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 affected58 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0003 affected58 at risk
Dry skin	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0003 affected58 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00014 affected58 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0005 affected58 at risk
Hypertension	Vascular disorders	Systematic Assessment	EG0005 affected58 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0004 affected58 at risk

ID	Term
C000613593	durvalumab
D007074	Immunoglobulin G
D004220	Disulfides
C520704	tremelimumab

ID	Term
D007132	Immunoglobulin Isotypes
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D013440	Sulfides
D000838	Anions
D007477	Ions
D004573	Electrolytes
D007287	Inorganic Chemicals
D006862	Hydrogen Sulfide
D013457	Sulfur Compounds
D009930	Organic Chemicals

ID	Title	Description
BG000	Primary PD-(L)1 Resistance Cohort	Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.
BG001	Acquired PD-(L)1 Resistance Cohort	Prior response to immune checkpoint inhibitor monotherapy included 24 weeks or more of disease control (complete response, partial response, or stable disease) after initiation of single agent anti-PD-1/PD-L1 therapy that had subsequently progressed after 24 weeks.
BG002	Total	Total of all reporting groups