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 (DARZALEX)

A Phase 1b/2, Open-Label, Randomized Study of Daratumumab Administered in Combination With Atezolizumab Compared With Atezolizumab Alone in Subjects With Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer

The purpose of the study is to compare the overall response rate (ORR) in non-small cell lung cancer (NSCLC) participants treated with daratumumab in combination with atezolizumab versus atezolizumab alone.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Atezolizumab; Drug: Daratumumab

Detailed Description

This randomized (study medication assigned to participants by chance), multicenter study will provide study treatment (atezolizumab alone or atezolizumab+daratumumab) to participants with previously treated advanced or metastatic NSCLC to assess the anti-tumor activity and safety. Participants who receive atezolizumab treatment with confirmed disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be eligible to crossover to treatment (atezolizumab + daratumumab) if they meet crossover eligibility criteria. It is expected that 100 participants will enroll in the study including 6 participants in the safety run in phase. Data Monitoring Committee (DMC) will review ongoing data, and may formulate recommendations on study conduct, including expansion of enrollment of some PD-L1 subgroups, resulting in greater than 96 participants. The participants in the safety run in phase will be administered the combination of daratumumab and atezolizumab to determine the safety and tolerability that will be evaluated by the Safety Evaluation Team (SET) for dose limiting toxicity before the random assignment of participants in a 1:1 ratio in 2 treatment arms. The study consists of 3 phases: Screening Phase (up to 28 days), Treatment Phase and Post-Treatment Follow-up Phase which will continue until death, lost to follow-up, withdrawal of consent, or the End of the Study [the study end is approximately 6 to 12 months after that last participant is enrolled]. Participants will undergo tumor assessments (RECIST 1.1), immunogenicity, pharmacokinetics, biomarkers and safety evaluations (adverse events, laboratory tests, electrocardiogram [ECGs], vital sign measurements, physical examinations, Eastern Cooperative Oncology Group [ECOG] performance status score) over the time.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
  • Boulogne Billancourt, France
  • Caen Cedex, France
  • Creteil, France
  • Haut-Rhin, France
  • Montpellier, France
  • Nancy, France
  • Paris, France
  • Rennes cedex 9, France
  • Rouen, France
  • Suresnes, France
  • Vandoeuvre les Nancy, France
• Hungary
  • Budapest, Hungary
  • Szekesfehervar, Hungary
  • Tatabanya, Hungary
• Poland
  • Lodz, Poland
  • Otwock, Poland
  • Wieliszew, Poland
• Spain
  • Barcelona, Spain
  • Elche, Spain
  • Jaén, Spain
  • Leganés, Spain
  • Madrid, Spain
  • Murcia, Spain
  • Málaga, Spain
  • Palma de Mallorca, Spain
  • Pozuelo de Alarcón, Spain
  • San Sebastián, Spain
  • Sótano, Spain
  • Valencia, Spain
  • Zaragoza, Spain
• United States
  • California
    • Loma Linda, California, United States
    • Whittier, California, United States
  • Delaware
    • Newark, Delaware, United States
  • Florida
    • Deerfield Beach, Florida, United States
    • Fort Lauderdale, Florida, United States
    • Orlando, Florida, United States
    • Tampa, Florida, United States
  • Georgia
    • Athens, Georgia, United States
    • Atlanta, Georgia, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Maryland
    • Bethesda, Maryland, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Tennessee
    • Chattanooga, Tennessee, United States
    • Knoxville, Tennessee, United States
    • Nashville, Tennessee, United States
  • Washington
    • Spokane, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Have histologically or cytologically confirmed advanced or metastatic non-small cell lung cancer (NSCLC) (Stage IIIb or greater)
• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Tumor cell programmed death-ligand 1 (PD-L1) score of tumor cells (TC)1-3 and immune cell PD-L1 score of tumor-infiltrating immune cells (IC)0-3 as determined by an immunohistochemistry (IHC) assay performed by the central laboratory on tissue obtained after the last line of therapy
• A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta- hCG]) at Screening within 14 days prior to study drug administration

Inclusion Criteria for Crossover:

• Participants must have been randomized to Arm A of the study and had radiographic disease progression according to RECIST 1.1
• Participants must have a mandatory biopsy at the time of disease progression according to RECIST 1.1 prior to crossing over. If not clinically feasible, discussion with Sponsor is required
• The first dose of atezolizumab in the crossover arm should be within 42 days of last dose but no less than 21 days from the last dose prior to crossing over

Exclusion Criteria:

• Received any of the following prescribed medications or therapies in the past:

  1. Anti-cluster of differentiation(CD)38 therapy, including daratumumab
  2. CD137 agonists, immune checkpoint inhibitors including but not limited to CTLA-4, anti-PD-1, and anti-PD-L1 therapies
• Known to be seropositive for human immunodeficiency virus (HIV)
• Prior allogeneic bone marrow transplantation or solid organ transplant
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Active hepatitis B, defined by a positive test for hepatitis B surface antigen [HBsAg] or prior history of hepatitis B, defined by presence of antibodies to hepatitis B core antigen [anti-HBc], regardless of hepatitis B surface antibody [anti-HBs] status; active hepatitis C or prior history of hepatitis C (anti-HCV positive), except in the setting of a sustained virologic response (SVR), defined as aviremia 12 weeks after completion of antiviral therapy. If hepatitis C virus (HCV) antibodies are detected, an HCV RNA test for viral load by polymerase chain reaction (PCR) should be performed at least 12 weeks after completion of antiviral therapy to rule out active infection

Exclusion Criteria for Crossover:

• Received any subsequent anti-cancer therapies from the time between the last dose of atezolizumab prior to the first administration of study drug after crossing over
• Whole brain radiation within 28 days or other radiotherapy within 14 days prior to first administration of study drug after crossing over

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm A: Atezolizumab; Participants in Treatment Arm A will receive Atezolizumab 1,200 milligram (mg) intravenously (IV) on Day 1 of every 21-day cycle. Participants with confirmed disease progression based on RECIST 1.1 may cross over to Arm B and receive daratumumab and atezolizumab, provided crossover eligibility criteria are met.	Drug: Atezolizumab; Participants will receive atezolizumab 1200 mg intravenously.
Experimental: Treatment Arm B: Atezolizumab and Daratumumab; Participants will receive daratumumab 16 milligram per kilogram [mg/kg] (Safety Run-in and Treatment Arm B) Intravenously (IV) weekly for 3 cycles (Day 1, 8 and 15), and Day 1 of every 21-day cycle thereafter. Atezolizumab will be administered at 1200 mg IV on Day 2 of Cycle 1 and on Day 1 of every 21-day cycle thereafter. Participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met.	Drug: Atezolizumab; Participants will receive atezolizumab 1200 mg intravenously.; Drug: Daratumumab; Participants will receive daratumumab 16 mg/kg intravenously.; Other Names: JNJ-54767414

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Overall Response Rate (ORR)	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'.	Up to 1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	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'.	Up to 1.5 years
Duration of Response (DoR)	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'.	Up to 1.5 years
Clinical Benefit Rate	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'.	Up to 1.5 years
Progression-Free Survival (PFS)	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'.	Up to 1.5 years
Overall Survival (OS)	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'.	Up to 1.5 years
Daratumumab Serum Concentration	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'.	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)
Atezolizumab Serum Concentration	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'.	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)
Number of Participants With Anti-Daratumumab Antibodies	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'.	Up to 1.5 years
Number of Participants With Anti-Atezolizumab Antibodies	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'.	Up to 1.5 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Collaborators: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2016
• Primary Completion (Actual): May 17, 2018
• Study Completion (Actual): September 26, 2019

Study Registration Dates

• First Submitted: December 9, 2016
• First Submitted That Met QC Criteria: January 13, 2017
• First Posted (Estimate): January 18, 2017

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: November 5, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Daratumumab; Atezolizumab
• Other Study ID Numbers: CR108256; 2016-002579-83 (EudraCT Number); 54767414LUC2001 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No