Clinical trial NCT03023423: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2017-01-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Overall Response Rate (ORR)
timeFrame: Up to 1.5 years
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Up to 1.5 years
measure: Duration of Response (DoR)
timeFrame: Up to 1.5 years
measure: Clinical Benefit Rate
timeFrame: Up to 1.5 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 1.5 years
measure: Overall Survival (OS)
timeFrame: Up to 1.5 years
measure: Daratumumab Serum Concentration
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)
measure: Atezolizumab Serum Concentration
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)
measure: Number of Participants With Anti-Daratumumab Antibodies
timeFrame: Up to 1.5 years
measure: Number of Participants With Anti-Atezolizumab Antibodies
timeFrame: Up to 1.5 years
Other outcomes:
Locations:
city: Loma Linda
country: United States
state: California
city: Whittier
country: United States
state: California
city: Newark
country: United States
state: Delaware
city: Deerfield Beach
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Athens
country: United States
state: Georgia
city: Atlanta
country: United States
state: Georgia
city: New Orleans
country: United States
state: Louisiana
city: Bethesda
country: United States
state: Maryland
city: Oklahoma City
country: United States
state: Oklahoma
city: Chattanooga
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Spokane
country: United States
state: Washington
city: Bordeaux
country: France
city: Boulogne Billancourt
country: France
city: Caen Cedex
country: France
city: Creteil
country: France
city: Haut-Rhin
country: France
city: Montpellier
country: France
city: Nancy
country: France
city: Paris
country: France
city: Rennes cedex 9
country: France
city: Rouen
country: France
city: Suresnes
country: France
city: Vandoeuvre les Nancy
country: France
city: Budapest
country: Hungary
city: Szekesfehervar
country: Hungary
city: Tatabanya
country: Hungary
city: Lodz
country: Poland
city: Otwock
country: Poland
city: Wieliszew
country: Poland
city: Barcelona
country: Spain
city: Elche
country: Spain
city: Jaén
country: Spain
city: Leganés
country: Spain
city: Madrid
country: Spain
city: Murcia
country: Spain
city: Málaga
country: Spain
city: Palma de Mallorca
country: Spain
city: Pozuelo de Alarcón
country: Spain
city: San Sebastián
country: Spain
city: Sótano
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: