Trial Outcomes & Findings for Durvalumab and Tremelimumab in Treating Patients With Recurrent Stage IV Lung Cancer (NCT NCT03373760)

Last Updated: 2023-06-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

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

Results posted on

2023-06-09

Participant Flow

67 patients were initially enrolled. 7 patients were ineligible for study; 6 did not receive anti-PD-L1 monotherapy as their most recent line of treatment and 1 had inadequate documentation of measurable disease. Another 2 patients were ineligible for analysis, as 1 expired prior to receiving any treatment and 1 withdrew consent prior to treatment. In all, 58 eligible patients received protocol therapy, 28 in the primary resistance cohort and 30 in the acquired resistance cohort.

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	58
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	58

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Adverse Event	8
Overall Study Disease Progression	46
Overall Study Death	4

Baseline Characteristics

Durvalumab and Tremelimumab in Treating Patients With Recurrent Stage IV Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Primary PD-(L)1 Resistance Cohort n=28 Participants Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.	Acquired PD-(L)1 Resistance Cohort n=30 Participants 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.	Total n=58 Participants Total of all reporting groups
Age, Continuous	67.6 years n=5 Participants	67.8 years n=7 Participants	67.7 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized Race : White	24 participants n=5 Participants	26 participants n=7 Participants	50 participants n=5 Participants
Race/Ethnicity, Customized Race : Black	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Race : Native American	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Race : Not reported	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Hispanic ethnicity	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Number of prior lines of therapy for stage IV disease <2	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Number of prior lines of therapy for stage IV disease ≥2 (max 4)	19 Participants n=5 Participants	18 Participants n=7 Participants	37 Participants n=5 Participants
Progression-free survival on prior anti-PD- ( L)1 therapy	3.0 months n=5 Participants	10.0 months n=7 Participants	5.5 months n=5 Participants
Best response to prior anti-PD- ( L)1 therapy Complete response	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Best response to prior anti-PD- ( L)1 therapy Partial response	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Best response to prior anti-PD- ( L)1 therapy Stable disease	11 Participants n=5 Participants	20 Participants n=7 Participants	31 Participants n=5 Participants
Best response to prior anti-PD- ( L)1 therapy Progressive disease	15 Participants n=5 Participants	0 Participants n=7 Participants	15 Participants n=5 Participants
Performance status 0	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Performance status 1	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants
Smoking status Current smoker	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Smoking status Former smoker	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Smoking status Never smoker	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Weight loss ≥10% in the 6 months prior to baseline	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
PD-L1 expression (TPS (%)) <1%	10 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants
PD-L1 expression (TPS (%)) 1%-49%	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
PD-L1 expression (TPS (%)) 50%	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
PD-L1 expression (TPS (%)) Unknown	8 Participants n=5 Participants	16 Participants n=7 Participants	24 Participants n=5 Participants
Tumor mutational burden <10 mt/Mb	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Tumor mutational burden ≥10 mt/Mb	17 Participants n=5 Participants	17 Participants n=7 Participants	34 Participants n=5 Participants
Tumor mutational burden Not evaluable	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

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

Population: Eligible and evaluable participants

Outcome measures

Outcome measures
Measure	Primary PD-(L)1 Resistance Cohort n=28 Participants Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.	Acquired PD-(L)1 Resistance Cohort n=30 Participants 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.
Objective Response Rate	7 percentage of participants Interval 0.0 to 17.0	0 percentage of participants There were 0 responses in the acquired resistance cohort so 95% confidence interval is not applicable here.

SECONDARY outcome

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

Population: Eligible and evaluable participants.

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

Outcome measures

Outcome measures
Measure	Primary PD-(L)1 Resistance Cohort n=2 Participants Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.	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.
Duration of Response (DoR) Among Patients Who Achieve a Complete Response (CR) or Partial Response (PR) (Confirmed and Unconfirmed) by RECIST 1.1. Duration of response for the first responding patient in the primary resistance cohort	8.5 months	—
Duration of Response (DoR) Among Patients Who Achieve a Complete Response (CR) or Partial Response (PR) (Confirmed and Unconfirmed) by RECIST 1.1. Duration of response for the second responding patient in the primary resistance cohort	5.9 months	—

SECONDARY outcome

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

Population: Data were not collected for this outcome.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: Eligible and evaluable participants

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.

Outcome measures

Outcome measures
Measure	Primary PD-(L)1 Resistance Cohort n=28 Participants Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.	Acquired PD-(L)1 Resistance Cohort n=30 Participants 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.
Overall Survival (OS) Among Patients Treated With MEDI4736 (Durvalumab) Plus Tremelimumab	7.7 months Interval 4.0 to 12.0	7.6 months Interval 5.3 to 10.2

SECONDARY outcome

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

Population: Eligible and evaluable participants

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.

Outcome measures

Outcome measures
Measure	Primary PD-(L)1 Resistance Cohort n=28 Participants Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.	Acquired PD-(L)1 Resistance Cohort n=30 Participants 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.
Investigator-assessed Progression-free Survival (IA-PFS) Among Patients Treated With MEDI4736 (Durvalumab) Plus Tremelimumab.	2.0 months Interval 1.6 to 3.0	2.1 months Interval 1.6 to 3.2

SECONDARY outcome

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

Population: Data were not collected for this outcome.

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) will be used as the date of progression. 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: Participants who received at least one dose of protocol treatment

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).

Outcome measures

Outcome measures
Measure	Primary PD-(L)1 Resistance Cohort n=58 Participants Prior response to immune checkpoint inhibitor monotherapy included disease progression within 24 weeks of initiation of single agent anti-PD-1/PD-L1 therapy.	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.
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Atrial flutter	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Chills	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dyspnea	5 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Encephalopathy	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Platelet count decreased	3 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Rash maculo-papular	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Vomiting	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs White blood cell decreased	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Atrial fibrillation	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Confusion	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Creatinine increased	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Death NOS	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Dehydration	3 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Diarrhea	4 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Fatigue	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Febrile neutropenia	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Generalized muscle weakness	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hyperglycemia	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Hypoxia	2 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lung infection	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Lymphocyte count decreased	3 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Nausea	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Neutrophil count decreased	1 Participants	—
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Pneumonitis	2 Participants	—

Adverse Events

MEDI4736 + Tremelimumab

Serious events: 36 serious events

Other events: 58 other events

Deaths: 47 deaths

Serious adverse events

Serious adverse events
Measure	MEDI4736 + Tremelimumab n=58 participants at risk 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
Infections and infestations Skin infection	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Injury, poisoning and procedural complications Fall	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Injury, poisoning and procedural complications Hip fracture	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Alanine aminotransferase increased	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Aspartate aminotransferase increased	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Blood bilirubin increased	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Creatinine increased	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Electrocardiogram QT corrected interval prolonged	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Fibrinogen decreased	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Lymphocyte count decreased	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Neutrophil count decreased	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Esophagitis	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Nausea	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Vomiting	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
General disorders Chills	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
General disorders Death NOS	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
General disorders Fatigue	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Infections and infestations Lung infection	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Blood and lymphatic system disorders Anemia	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Blood and lymphatic system disorders Febrile neutropenia	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Cardiac disorders Atrial fibrillation	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Cardiac disorders Atrial flutter	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Cardiac disorders Cardiac arrest	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Cardiac disorders Heart failure	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Colitis	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Diarrhea	15.5% 9/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Esophageal obstruction	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Platelet count decreased	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Serum amylase increased	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations White blood cell decreased	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Anorexia	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Dehydration	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hypokalemia	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hyponatremia	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified - Other	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Nervous system disorders Dizziness	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Nervous system disorders Encephalopathy	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Nervous system disorders Peripheral sensory neuropathy	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Nervous system disorders Syncope	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Psychiatric disorders Confusion	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Renal and urinary disorders Hematuria	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Cough	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Dyspnea	12.1% 7/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Hypoxia	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Resp, thoracic and mediastinal disorders - Other	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Skin and subcutaneous tissue disorders Bullous dermatitis	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.4% 2/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Vascular disorders Hematoma	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Vascular disorders Thromboembolic event	1.7% 1/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.

Other adverse events

Other adverse events
Measure	MEDI4736 + Tremelimumab n=58 participants at risk 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
Blood and lymphatic system disorders Anemia	41.4% 24/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Cardiac disorders Atrial fibrillation	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Endocrine disorders Endocrine disorders-Other	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Endocrine disorders Hypothyroidism	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Abdominal pain	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Constipation	12.1% 7/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Diarrhea	20.7% 12/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Dysphagia	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Nausea	27.6% 16/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Gastrointestinal disorders Vomiting	17.2% 10/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
General disorders Chills	10.3% 6/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
General disorders Edema limbs	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
General disorders Fatigue	41.4% 24/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
General disorders Fever	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
General disorders Non-cardiac chest pain	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
General disorders Pain	12.1% 7/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Infections and infestations Bronchial infection	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Infections and infestations Infections and infestations-Other	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Infections and infestations Lung infection	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Infections and infestations Urinary tract infection	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Alanine aminotransferase increased	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Alkaline phosphatase increased	15.5% 9/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Aspartate aminotransferase increased	10.3% 6/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Creatinine increased	12.1% 7/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Investigations-Other	10.3% 6/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Lymphocyte count decreased	25.9% 15/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Platelet count decreased	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations Weight loss	22.4% 13/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Investigations White blood cell decreased	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Anorexia	27.6% 16/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Dehydration	12.1% 7/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hypercalcemia	13.8% 8/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hyperglycemia	20.7% 12/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hyperkalemia	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hypernatremia	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hypoalbuminemia	34.5% 20/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hypocalcemia	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hypokalemia	20.7% 12/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hypomagnesemia	12.1% 7/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hyponatremia	31.0% 18/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Metabolism and nutrition disorders Hypophosphatemia	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Musculoskeletal and connective tissue disorders Arthralgia	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Musculoskeletal and connective tissue disorders Back pain	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Musculoskeletal and connective tissue disorders Bone pain	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	12.1% 7/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Musculoskeletal and connective tissue disorders Myalgia	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Musculoskeletal and connective tissue disorders Pain in extremity	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Nervous system disorders Dizziness	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Nervous system disorders Dysgeusia	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Nervous system disorders Headache	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Nervous system disorders Peripheral sensory neuropathy	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Psychiatric disorders Anxiety	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Psychiatric disorders Depression	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Psychiatric disorders Insomnia	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Renal and urinary disorders Urinary incontinence	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Cough	24.1% 14/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Dyspnea	43.1% 25/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Hoarseness	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Hypoxia	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Productive cough	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Resp, thoracic and mediastinal disorders - Other	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Respiratory, thoracic and mediastinal disorders Sore throat	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Skin and subcutaneous tissue disorders Dry skin	5.2% 3/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Skin and subcutaneous tissue disorders Pruritus	24.1% 14/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Vascular disorders Hypertension	8.6% 5/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.
Vascular disorders Hypotension	6.9% 4/58 • Duration of treatment and follow-up until death or 3 years post registration CTCAE Version 4.0 was used for routine toxicity reporting and CTCAE Version 5.0 was used for Serious Adverse Event (SAE) reporting. 58 participants were assessed for AEs: 28 in the primary PD-L1 resistance cohort and 30 in the acquired PD-L1 resistance cohort.

Additional Information

Lung Committee Statistician

SWOG Statistics and Data Management Center

Phone: 2066674623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place