Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 3 for:    LUC2001

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03023423
Recruitment Status : Active, not recruiting
First Posted : January 18, 2017
Results First Posted : July 23, 2019
Last Update Posted : August 7, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Atezolizumab Drug: Daratumumab Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 23, 2016
Actual Primary Completion Date : May 17, 2018
Estimated Study Completion Date : September 15, 2020

Resource links provided by the National Library of Medicine


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 Name: JNJ-54767414




Primary Outcome Measures :
  1. Percentage of Participants With Overall Response Rate (ORR) [ Time Frame: Up to 1.5 years ]
    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'.


Secondary Outcome Measures :
  1. Number of Participants With Adverse Events [ Time Frame: Up to 1.5 years ]
    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'.

  2. Duration of Response (DoR) [ Time Frame: Up to 1.5 years ]
    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'.

  3. Clinical Benefit Rate [ Time Frame: Up to 1.5 years ]
    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'.

  4. Progression-Free Survival (PFS) [ Time Frame: Up to 1.5 years ]
    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'.

  5. Overall Survival (OS) [ Time Frame: Up to 1.5 years ]
    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'.

  6. Daratumumab Serum Concentration [ Time Frame: 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) ]
    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'.

  7. Atezolizumab Serum Concentration [ Time Frame: 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) ]
    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'.

  8. Number of Participants With Anti-Daratumumab Antibodies [ Time Frame: Up to 1.5 years ]
    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'.

  9. Number of Participants With Anti-Atezolizumab Antibodies [ Time Frame: 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'.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03023423


  Show 47 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Genentech, Inc.
Investigators
Layout table for investigator information
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:
Statistical Analysis Plan  [PDF] September 19, 2018
Study Protocol  [PDF] October 4, 2018


Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03023423     History of Changes
Other Study ID Numbers: CR108256
2016-002579-83 ( EudraCT Number )
54767414LUC2001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: January 18, 2017    Key Record Dates
Results First Posted: July 23, 2019
Last Update Posted: August 7, 2019
Last Verified: July 2019

Layout table for additional information
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Atezolizumab
Daratumumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs