Trial Outcomes & Findings for Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Resectable Non-Small Cell Lung Cancer (NCT NCT03794544)

Last Updated: 2022-02-24

Results Overview

Major pathological response rate is defined as percentage of participants with \<=10% residual viable tumor cells in the resected specimen.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

84 participants

Primary outcome timeframe

Day 1 through Day 42

Results posted on

2022-02-24

Participant Flow

The trial was interrupted due to COVID-19 pandemic from 13Apr2020 to 07May2020.

Participant milestones

Participant milestones
Measure	Durvalumab 1500 mg + Monalizumab 750 mg Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
Overall Study STARTED	20	16	27	21
Overall Study Treated	20	16	26	21
Overall Study COMPLETED	19	15	26	18
Overall Study NOT COMPLETED	1	1	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Durvalumab 1500 mg + Monalizumab 750 mg Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
Overall Study Withdrawal by Subject	0	0	1	1
Overall Study Death	0	1	0	0
Overall Study Lost to Follow-up	1	0	0	1
Overall Study Other	0	0	0	1

Baseline Characteristics

Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Resectable Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab 1500 mg n=27 Participants Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg n=21 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Monalizumab 750 mg n=20 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg n=16 Participants Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Total n=84 Participants Total of all reporting groups
Age, Continuous	67.1 Years STANDARD_DEVIATION 9.0 • n=5 Participants	65.5 Years STANDARD_DEVIATION 7.5 • n=7 Participants	65.1 Years STANDARD_DEVIATION 6.3 • n=5 Participants	72.9 Years STANDARD_DEVIATION 7.9 • n=4 Participants	67.3 Years STANDARD_DEVIATION 8.2 • n=21 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	34 Participants n=21 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	10 Participants n=4 Participants	50 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	14 Participants n=4 Participants	81 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	20 Participants n=7 Participants	19 Participants n=5 Participants	13 Participants n=4 Participants	75 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 42

Population: The ITT population included participants who were randomized and were analyzed according to their randomized treatment group.

Major pathological response rate is defined as percentage of participants with \<=10% residual viable tumor cells in the resected specimen.

Outcome measures

Outcome measures
Measure	Durvalumab 1500 mg n=27 Participants Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg n=21 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Monalizumab 750 mg n=20 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg n=16 Participants Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
Major Pathological Response Rate	11.1 Percentage of participants Interval 2.4 to 29.2	19.0 Percentage of participants Interval 5.4 to 41.9	30.0 Percentage of participants Interval 11.9 to 54.3	31.3 Percentage of participants Interval 11.0 to 58.7

SECONDARY outcome

Timeframe: Day 1 through Day 42

Population: The ITT population included participants who were randomized and were analyzed according to their randomized treatment group.

The pCR rate is defined as percentage of participants with no residual viable tumor cells in the resected specimen.

Outcome measures

Outcome measures
Measure	Durvalumab 1500 mg n=27 Participants Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg n=21 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Monalizumab 750 mg n=20 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg n=16 Participants Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
Pathological Complete Response (pCR) Rate	3.7 Percentage of participants Interval 0.1 to 19.0	9.5 Percentage of participants Interval 1.2 to 30.4	10.0 Percentage of participants Interval 1.2 to 31.7	12.5 Percentage of participants Interval 1.6 to 38.3

SECONDARY outcome

Timeframe: Day 29 to Day 42 after Week 1 Day 1

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

Feasibility to surgery is defined as the percentage of participants who underwent the planned surgery within Days 29 to 42 after Week 1 Day 1.

Outcome measures

Outcome measures
Measure	Durvalumab 1500 mg n=26 Participants Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg n=21 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Monalizumab 750 mg n=20 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg n=16 Participants Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
Feasibility to Surgery	84.6 Percentage of participants Interval 0.1 to 19.0	81.0 Percentage of participants Interval 1.2 to 30.4	90.0 Percentage of participants Interval 1.2 to 31.7	93.8 Percentage of participants Interval 1.6 to 38.3

SECONDARY outcome

Timeframe: From Day 1 through Day 105

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

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

Outcome measures

Outcome measures
Measure	Durvalumab 1500 mg n=26 Participants Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg n=21 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Monalizumab 750 mg n=20 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg n=16 Participants Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TEAEs	18 Participants	19 Participants	15 Participants	13 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TESAEs	3 Participants	2 Participants	1 Participants	5 Participants

SECONDARY outcome

Timeframe: From Day 1 through Day 105

Population: As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received. 'Number Analyzed' denotes the participants analyzed for the specified laboratory parameters.

Participants with Grade 3 or Grade 4 clinical laboratory toxicities are reported. Laboratory tests included hematology, coagulation, chemistry, and urinalysis.

Outcome measures

Outcome measures
Measure	Durvalumab 1500 mg n=26 Participants Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg n=21 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Monalizumab 750 mg n=20 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg n=16 Participants Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities Alanine aminotransferase increased	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities Gamma glutamyl transferase increased	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities Lipase increased	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities Hyponatremia	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Grade 3 or Grade 4 Clinical Laboratory Toxicities Lymphocyte count decreased	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From Day 1 through Day 105

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

Participants with abnormal vital sign reported as TEAEs are reported.

Outcome measures

Outcome measures
Measure	Durvalumab 1500 mg n=26 Participants Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg n=21 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Monalizumab 750 mg n=20 Participants Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg n=16 Participants Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
Number of Participants With Abnormal Vital Signs Reported as TEAEs Palpitations	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Pyrexia	1 Participants	2 Participants	1 Participants	0 Participants

Adverse Events

Durvalumab 1500 mg

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Durvalumab 1500 mg + Oleclumab 3000 mg

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Durvalumab 1500 mg + Monalizumab 750 mg

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Durvalumab 1500 mg + Danvatirsen 200 mg

Serious events: 5 serious events

Other events: 13 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Durvalumab 1500 mg n=26 participants at risk Participants received durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W; on Week 1 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Oleclumab 3000 mg n=21 participants at risk Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and oleclumab 3000 mg IV every 2 weeks (Q2W; on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Monalizumab 750 mg n=20 participants at risk Participants received durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and monalizumab 750 mg IV Q2W (on Week 1 Day 1 and Week 3 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).	Durvalumab 1500 mg + Danvatirsen 200 mg n=16 participants at risk Participants received danvatirsen 200 mg IV on Days 1, 3, and 5 of Week 0 (7-day danvatirsen lead-in period), followed by durvalumab 1500 mg IV Q4W (on Week 1 Day 1) and danvatirsen 200 mg IV every week (on Week 1 Day 1, Week 2 Day 1, Week 3 Day 1, and Week 4 Day 1) until disease progression, unacceptable toxicity, or other reason of treatment discontinuation over a 28-day treatment period. Surgical resection was planned between Day 29 and Day 42. After surgical resection, participants were followed up to Day 105 (starting from Week 1 Day 1).
Cardiac disorders Pericarditis	3.8% 1/26 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/16 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Infections and infestations Covid-19	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	6.2% 1/16 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Infections and infestations Pneumonia	3.8% 1/26 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	4.8% 1/21 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	6.2% 1/16 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Infections and infestations Wound infection	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	6.2% 1/16 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Injury, poisoning and procedural complications Bronchial anastomosis complication	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	6.2% 1/16 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	6.2% 1/16 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	4.8% 1/21 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/16 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Immune-mediated arthritis	3.8% 1/26 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/16 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Renal and urinary disorders Renal infarct	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	6.2% 1/16 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	6.2% 1/16 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	6.2% 1/16 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/21 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	5.0% 1/20 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/16 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary air leakage	0.00% 0/26 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	4.8% 1/21 • Number of events 1 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/20 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.	0.00% 0/16 • From Day 1 through Day 105 As-treated population was considered for collecting AEs data. As-treated population included all participants who received any study drug and analyzed according to the treatment they actually received.

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Publication restrictions are in place

Restriction type: OTHER