Trial Outcomes & Findings for A Study of Daratumumab in Combination With Atezolizumab Compared With Atezolizumab Alone in Participants With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer (NCT NCT03023423)

Last Updated: 2019-11-20

Results Overview

ORR was defined as the percentage of participants with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Criteria for CR: Disappearance of all target lesions; all lymph nodes must be of non-pathological in size (less than \[\<\]10 millimeter \[mm\] short axis; normalization of tumor marker level. Criteria for PR: greater than or equal to (\>=)30 percent (%) decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Overall Response (OR) = CR + PR. The outcome measure (OM) was planned to be reported for participants based on their initial assignment to Randomized Phase: Atezolizumab'.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

100 participants

Primary outcome timeframe

Up to 1.5 years

Results posted on

2019-11-20

Participant Flow

A total of 100 participants were enrolled in the study (7 in phase 1b \[safety run-in phase\], and 93 in Phase 2 \[randomized phase\]). Among them, 99 participants (7 in phase 1b \[safety run-in phase\], and 92 in phase 2 \[randomized phase\]) were randomized as 1 participant was randomized after the clinical cutoff date (17-May-2018).

Participant milestones

Participant milestones
Measure	Safety Run-in Phase: Daratumumab + Atezolizumab Participants received daratumumab (Dara) 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab (Atezo) IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezolizumab Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.
Overall Study STARTED	7	46	46
Overall Study Treated	7	44	44
Overall Study Crossover From Atezo to Dara + Atezo	0	8	0
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	7	46	46

Reasons for withdrawal

Reasons for withdrawal
Measure	Safety Run-in Phase: Daratumumab + Atezolizumab Participants received daratumumab (Dara) 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab (Atezo) IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezolizumab Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.
Overall Study Death	5	12	20
Overall Study Other	0	2	2
Overall Study Ongoing	2	32	24

Baseline Characteristics

A Study of Daratumumab in Combination With Atezolizumab Compared With Atezolizumab Alone in Participants With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Safety Run-in Phase: Daratumumab + Atezolizumab n=7 Participants Participants received daratumumab (Dara) 16 milligram per kilogram (mg/kg) intravenously (IV) weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab (Atezo) IV at a dose of 1200 milligram (mg) on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezolizumab n=46 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=46 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Total n=99 Participants Total of all reporting groups
Age, Continuous	61 years STANDARD_DEVIATION 9.73 • n=99 Participants	61.7 years STANDARD_DEVIATION 10.05 • n=107 Participants	63.2 years STANDARD_DEVIATION 10.76 • n=206 Participants	62.3 years STANDARD_DEVIATION 10.29 • n=7 Participants
Sex: Female, Male Female	3 Participants n=99 Participants	18 Participants n=107 Participants	8 Participants n=206 Participants	29 Participants n=7 Participants
Sex: Female, Male Male	4 Participants n=99 Participants	28 Participants n=107 Participants	38 Participants n=206 Participants	70 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=99 Participants	36 Participants n=107 Participants	40 Participants n=206 Participants	83 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	9 Participants n=107 Participants	6 Participants n=206 Participants	15 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) White	7 Participants n=99 Participants	35 Participants n=107 Participants	41 Participants n=206 Participants	83 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	11 Participants n=107 Participants	5 Participants n=206 Participants	16 Participants n=7 Participants
Race/Ethnicity, Customized Other	0 Participants n=99 Participants	11 Participants n=107 Participants	6 Participants n=206 Participants	17 Participants n=7 Participants
Race/Ethnicity, Customized White Non-Hispanic	7 Participants n=99 Participants	35 Participants n=107 Participants	40 Participants n=206 Participants	82 Participants n=7 Participants
Region of Enrollment FRANCE	0 Participants n=99 Participants	10 Participants n=107 Participants	6 Participants n=206 Participants	16 Participants n=7 Participants
Region of Enrollment HUNGARY	0 Participants n=99 Participants	8 Participants n=107 Participants	7 Participants n=206 Participants	15 Participants n=7 Participants
Region of Enrollment SPAIN	3 Participants n=99 Participants	19 Participants n=107 Participants	27 Participants n=206 Participants	49 Participants n=7 Participants
Region of Enrollment UNITED STATES	4 Participants n=99 Participants	9 Participants n=107 Participants	6 Participants n=206 Participants	19 Participants n=7 Participants
Time from initial diagnosis	10.3 months STANDARD_DEVIATION 9.29 • n=99 Participants	18.8 months STANDARD_DEVIATION 20.89 • n=107 Participants	17.6 months STANDARD_DEVIATION 14.17 • n=206 Participants	17.6 months STANDARD_DEVIATION 17.37 • n=7 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG Score 0	3 Participants n=99 Participants	19 Participants n=107 Participants	12 Participants n=206 Participants	34 Participants n=7 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG Score 1	4 Participants n=99 Participants	27 Participants n=107 Participants	33 Participants n=206 Participants	64 Participants n=7 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG Score 2	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants

PRIMARY outcome

Timeframe: Up to 1.5 years

Population: Intent-to-treat (ITT) analysis set included all participants who had entered the Randomized phase of the study.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=46 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=46 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Percentage of Participants With Overall Response Rate (ORR)	13.0 Percentage of participants Interval 4.9 to 26.3	4.3 Percentage of participants Interval 0.5 to 14.8	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years

Population: Safety analysis set included all participants who had received at least 1 administration of any study medication.

An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. Crossover participants were counted twice (in 'Randomized Phase: Atezo arm' and in 'Randomized Phase: Atezo Crossed Over to Dara + Atezo') for safety analysis. For cross-over participants, AEs after initiation of cross-over treatment were summarized separately in the crossover arm, however, AEs occurred before crossover treatment were included in 'Randomized Phase: Atezolizumab arm'.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=7 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=44 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=44 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo n=8 Participants Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Number of Participants With Adverse Events	7 Participants	42 Participants	44 Participants	8 Participants

SECONDARY outcome

Timeframe: Up to 1.5 years

Population: ITT analysis set included all participants who had entered the Randomized phase of the study. Here, N (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Duration of response was defined as duration from date of initial documentation of disease response to date of first objectively documented evidence of recurrence or progressive disease (PD) or death, whichever occurred first. PD: Sum of diameters increased by \>=20% and \>=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for "unequivocal progression" based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease \[SD\]/PR). Participants without measurable disease: for "unequivocal progression" of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=6 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=2 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Duration of Response (DoR)	5.8 Months Interval 2.2 to 5.8	2.9 Months Here NA signifies that the lower and upper limit of 95% Confidence Interval (CI) were not estimable due to lesser number of participants with events.	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years

Population: ITT analysis set included all participants who had entered the Randomized phase of the study.

Clinical benefit rate was defined as percentage of participants who achieved disease control (CR, PR, or SD). RECIST 1.1 Criteria for CR: Disappearance of all target lesions; all lymph nodes of non-pathological in size (\<10 mm short axis); normalization of tumor marker level. Criteria for PR: \>=30 % decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. Criteria for SD: \<30% decrease in sum of diameters of all target lesions compared with baseline and \<20% increase compared with nadir, in absence of new lesions or unequivocal progression of nontarget lesions. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=46 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=46 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Clinical Benefit Rate	43.5 Percentage of Participants Interval 28.9 to 58.9	52.2 Percentage of Participants Interval 36.9 to 67.1	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years

Population: ITT analysis set included all participants who had entered the Randomized phase of the study.

PFS was defined as the duration from the date of randomization until the first documented disease progression (PD) or death, whichever occurred first. PD: Sum of diameters increased by \>=20% and \>=5 millimeter (mm) from nadir (including baseline if it was smallest sum). Participants with measurable disease: for "unequivocal progression" based on non-target disease, overall level of substantial worsening that merits discontinuation of therapy (if target disease was stable disease \[SD\]/PR). Participants without measurable disease: for "unequivocal progression" of non-target disease, increase in overall tumor burden comparable to increase required for PD of measurable disease. Appearance of 1/ more new lesions or unequivocal progression of non-target lesion was also considered as PD. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=46 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=46 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Progression-Free Survival (PFS)	1.48 Months Interval 1.38 to 2.76	1.68 Months Interval 1.41 to 2.79	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years

Population: ITT analysis set included all participants who had entered the Randomized phase of the study.

Overall Survival was defined as the duration from the date of randomization to the date of participant's death due to any cause. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=46 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=46 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Overall Survival (OS)	NA Months Interval 7.43 to Here NA signifies that the median and upper limit of 95% CI were not estimable due to lesser number of events.	7.13 Months Interval 3.52 to Here NA signifies that the upper limit of 95% CI was not estimable due to lesser number of events.	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 (C1D1):predose and postdose; C2D1 and C3D1:predose; C3D15: predose and postdose; C4D1: predose and postdose; C8D1: predose and postdose; C12D1: predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years)

Population: Pharmacokinetic (PK)-evaluable analysis set included all participants who had received at least 1 dose of daratumumab or atezolizumab and had at least 1 postinfusion sample collected. Here 'n' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure at a given time point.

Daratumumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=7 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=43 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Daratumumab Serum Concentration Cycle 1 Day 1 Predose	0.00 Microgram per milliliter (mcg/mL) Standard Deviation 0.000	0.00 Microgram per milliliter (mcg/mL) Standard Deviation 0.000	—	—
Daratumumab Serum Concentration Cycle 1 Day 1 Postdose	417.13 Microgram per milliliter (mcg/mL) Standard Deviation 141.626	296.12 Microgram per milliliter (mcg/mL) Standard Deviation 85.660	—	—
Daratumumab Serum Concentration Cycle 2 Day 1 Predose	393.95 Microgram per milliliter (mcg/mL) Standard Deviation 139.480	278.42 Microgram per milliliter (mcg/mL) Standard Deviation 89.340	—	—
Daratumumab Serum Concentration Cycle 3 Day 1 Predose	740.17 Microgram per milliliter (mcg/mL) Standard Deviation 99.515	487.65 Microgram per milliliter (mcg/mL) Standard Deviation 124.935	—	—
Daratumumab Serum Concentration Cycle 3 Day 15 Predose	843.22 Microgram per milliliter (mcg/mL) Standard Deviation 156.792	552.79 Microgram per milliliter (mcg/mL) Standard Deviation 180.549	—	—
Daratumumab Serum Concentration Cycle 3 Day 15 Postdose	1088.73 Microgram per milliliter (mcg/mL) Standard Deviation 282.349	827.72 Microgram per milliliter (mcg/mL) Standard Deviation 266.085	—	—
Daratumumab Serum Concentration Cycle 4 Day 1 Predose	899.90 Microgram per milliliter (mcg/mL) Standard Deviation 123.305	574.81 Microgram per milliliter (mcg/mL) Standard Deviation 181.193	—	—
Daratumumab Serum Concentration Cycle 4 Day 1 Postdose	1416.40 Microgram per milliliter (mcg/mL) Standard Deviation 353.415	856.30 Microgram per milliliter (mcg/mL) Standard Deviation 244.698	—	—
Daratumumab Serum Concentration Cycle 8 Day 1 Predose	254.87 Microgram per milliliter (mcg/mL) Standard Deviation NA Here NA signifies that Standard Deviation could not be calculated for a single participant.	288.84 Microgram per milliliter (mcg/mL) Standard Deviation 177.187	—	—
Daratumumab Serum Concentration Cycle 8 Day 1 Postdose	824.64 Microgram per milliliter (mcg/mL) Standard Deviation NA Here NA signifies that Standard Deviation could not be calculated for a single participant.	617.21 Microgram per milliliter (mcg/mL) Standard Deviation 239.962	—	—
Daratumumab Serum Concentration Cycle 12 Day 1 Predose	—	260.21 Microgram per milliliter (mcg/mL) Standard Deviation 17.163	—	—
Daratumumab Serum Concentration End of Treatment	405.14 Microgram per milliliter (mcg/mL) Standard Deviation 242.189	187.75 Microgram per milliliter (mcg/mL) Standard Deviation 110.531	—	—
Daratumumab Serum Concentration Post Last Dose	41.84 Microgram per milliliter (mcg/mL) Standard Deviation 23.082	112.63 Microgram per milliliter (mcg/mL) Standard Deviation 115.727	—	—

SECONDARY outcome

Timeframe: C1D1:predose and postdose; C1D2:predose and postdose; C2D1, C3D1:predose; C3D15:predose and postdose; C4D1:predose and postdose; C8D1:predose and postdose; C12D1:predose; end of treatment (37 days after last dose); and post last dose (up to 1.5 years)

Population: PK-evaluable analysis set: all participants who received at least 1 dose of daratumumab/atezolizumab and had at least 1 postinfusion sample collected. Here N (number of participants analyzed): participants evaluable for this outcome measure, and n (number of participants analyzed): participants evaluable for this outcome measure at given timepoint.

Atezolizumab serum concentrations were reported. Each cycle was of 21-days. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=7 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=39 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=39 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Atezolizumab Serum Concentration Post Last Dose	33.10 Microgram per milliliter (mcg/mL) Standard Deviation NA Here NA signifies that the standard deviation could not be calculated for a single participant.	13.17 Microgram per milliliter (mcg/mL) Standard Deviation 8.386	115.10 Microgram per milliliter (mcg/mL) Standard Deviation 146.937	—
Atezolizumab Serum Concentration Cycle 1 Day 1 Predose	—	0.00 Microgram per milliliter (mcg/mL) Standard Deviation 0.000	0.00 Microgram per milliliter (mcg/mL) Standard Deviation 0.000	—
Atezolizumab Serum Concentration Cycle 1 Day 1 Postdose	—	396.51 Microgram per milliliter (mcg/mL) Standard Deviation 103.196	440.00 Microgram per milliliter (mcg/mL) Standard Deviation 93.145	—
Atezolizumab Serum Concentration Cycle 1 Day 2 Predose	0.00 Microgram per milliliter (mcg/mL) Standard Deviation 0.000	—	0.00 Microgram per milliliter (mcg/mL) Standard Deviation 0.000	—
Atezolizumab Serum Concentration Cycle 1 Day 2 Postdose	362.14 Microgram per milliliter (mcg/mL) Standard Deviation 43.434	—	343.82 Microgram per milliliter (mcg/mL) Standard Deviation 135.476	—
Atezolizumab Serum Concentration Cycle 2 Day 1 Predose	91.16 Microgram per milliliter (mcg/mL) Standard Deviation 15.305	78.85 Microgram per milliliter (mcg/mL) Standard Deviation 30.575	81.90 Microgram per milliliter (mcg/mL) Standard Deviation 20.021	—
Atezolizumab Serum Concentration Cycle 3 Day 1 Predose	176.50 Microgram per milliliter (mcg/mL) Standard Deviation 33.234	117.61 Microgram per milliliter (mcg/mL) Standard Deviation 33.227	123.51 Microgram per milliliter (mcg/mL) Standard Deviation 31.882	—
Atezolizumab Serum Concentration Cycle 4 Day 1 Predose	166.50 Microgram per milliliter (mcg/mL) Standard Deviation 37.477	145.64 Microgram per milliliter (mcg/mL) Standard Deviation 37.323	157.79 Microgram per milliliter (mcg/mL) Standard Deviation 37.819	—
Atezolizumab Serum Concentration Cycle 4 Day 1 Postdose	612.25 Microgram per milliliter (mcg/mL) Standard Deviation 81.578	539.24 Microgram per milliliter (mcg/mL) Standard Deviation 116.291	482.33 Microgram per milliliter (mcg/mL) Standard Deviation 139.879	—
Atezolizumab Serum Concentration Cycle 8 Day 1 Predose	—	158.23 Microgram per milliliter (mcg/mL) Standard Deviation 77.778	—	—
Atezolizumab Serum Concentration Cycle 8 Day 1 Postdose	—	527.50 Microgram per milliliter (mcg/mL) Standard Deviation 213.492	515.25 Microgram per milliliter (mcg/mL) Standard Deviation 214.177	—
Atezolizumab Serum Concentration Cycle 12 Day 1 Predose	—	183.00 Microgram per milliliter (mcg/mL) Standard Deviation NA Here NA signifies that the standard deviation could not be calculated for a single participant.	248.00 Microgram per milliliter (mcg/mL) Standard Deviation NA Here NA signifies that the standard deviation could not be calculated for a single participant.	—
Atezolizumab Serum Concentration End of Treatment	136.43 Microgram per milliliter (mcg/mL) Standard Deviation 73.002	129.55 Microgram per milliliter (mcg/mL) Standard Deviation 79.720	141.62 Microgram per milliliter (mcg/mL) Standard Deviation 71.756	—

SECONDARY outcome

Timeframe: Up to 1.5 years

Population: The immunogenicity-evaluable analysis set included all participants who received at least 1 dose of atezolizumab or daratumumab and had appropriate samples for detection of antibodies to atezolizumab or daratumumab. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Number of participants with antibodies to daratumumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=7 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=37 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Number of Participants With Anti-Daratumumab Antibodies	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years

Number of participants with antibodies to atezolizumab (tested using a validated immunoassay method) were reported. The OM was planned to be reported for participants based on their initial assignment to 'Randomized Phase: Atezolizumab'.

Outcome measures

Outcome measures
Measure	Randomized Phase: Atezolizumab n=7 Participants Participants received atezolizumab IV at a dose of 1200 milligram (mg) on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=39 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Daratumumab + Atezolizumab n=38 Participants Participants received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol-defined treatment discontinuation criteria.	Randomized Phase: Atezo Crossed Over to Dara + Atezo Participants who crossed over from Atezolizumab arm (Randomized Phase) to Daratumumab + Atezolizumab arm (Randomized Phase) received daratumumab 16 mg/kg IV weekly on Days 1, 8, and 15 for first 3 cycles and then on Day 1 of each 21-day cycle thereafter along with atezolizumab IV at a dose of 1200 mg on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter until disease progression, unacceptable toxicity or other protocol defined treatment discontinuation criteria.
Number of Participants With Anti-Atezolizumab Antibodies	0 Participants	6 Participants	5 Participants	—

Adverse Events

Safety Run-in Phase: Daratumumab + Atezolizumab

Serious events: 4 serious events

Other events: 7 other events

Deaths: 5 deaths

Randomized Phase: Atezolizumab

Serious events: 15 serious events

Other events: 41 other events

Deaths: 9 deaths

Randomized Phase: Daratumumab + Atezolizumab

Serious events: 21 serious events

Other events: 41 other events

Deaths: 20 deaths

Randomized Phase: Atezo Crossed Over to Dara + Atezo

Serious events: 3 serious events

Other events: 8 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Executive Medical Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER