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)

Study Description

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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 IV; Drug: Dara-SC	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 approximately 132 participants will enroll in the study, including 6 participants in safety run in phase, 6 participants in the Dara-SC Phase 1b cohort, and 120 participants in the Phase 2 cohort. The Data Monitoring Committee (DMC) will review ongoing data, and may formulate recommendations on study conduct, including expansion of enrollment of some PD-L1 subgroups. 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 in the Phase 2 portion of the study. Additionally, the participants in the Phase 1b Dara-SC Cohort will be evaluated for safety. 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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	132 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
Estimated Primary Completion Date :	February 28, 2019
Estimated Study Completion Date :	October 14, 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Treatment Arm A: Atezolizumab; Participants in Treatment Arm A will receive Atezolizumab 1200 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 IV and atezolizumab, provided crossover eligibility criteria are met.	Drug: Atezolizumab; Participants will receive atezolizumab 1200 mg intravenously.
Experimental: Treatment Arm B: Atezolizumab and Daratumumab IV; Participants will receive daratumumab 16 milligram per kilogram [mg/kg] (Safety Run-in and Treatment Arm B) 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 IV; Participants will receive daratumumab 16 mg/kg intravenously.; Other Name: JNJ-54767414
Experimental: Phase 1b Cohort: Dara-SC and Atezolizumab; Participants will receive Dara-SC (subcutaneous formulation of daratumumab) by injection at a fixed dose of 1800 mg for 3 cycles (Day 1, 8 and 15), and Day 1 of every 21-day cycle thereafter. Atezolizumab will be administered at 1,200 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: Dara-SC; Participants will receive Dara-SC as a co-formulated drug product containing Recombinant Human Hyaluronidase PH20 (rHuPH20) (2000 Units per milliliter [U/mL]) and daratumumab (120 mg/mL) in a single vial (15 mL dose).; Other Name: JNJ-54767414

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants With Overall Response Rate (ORR) [ Time Frame: From randomization to end of study (an expected average of 3 years) ]
   ORR is 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. Per Response Evaluation Criteria In Solid Tumors Criteria for target lesions and assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), greater than or equal to (>=)30 percent (%) decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures :

1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Screening (28 days ) to end of treatment (30 days after the last dose) (Approximately 3 years) ]
2. Duration of Response (DoR) [ Time Frame: From randomization to the date of first documented evidence of Progressive Disease [PD] (an expected average of 3 years ]
   Duration of Response is defined as the duration from the date of the initial documentation of a response to the date of the first objectively documented evidence of progressive disease or death (At least 20% increase in the sum of the longest diameters of index lesions), whichever status is recorded first.
3. Percentage of Participants who Achieve Disease Control (CR, PR, or SD with duration of at least 16 weeks) Clinical Benefit Rate (CBR) [ Time Frame: From randomization to end of study (an expected average of 3 years) ]
   Clinical Benefit Rate is defined as the proportion of participants who achieve disease control (complete response [CR], Disappearance of all lesions; partial response [PR], greater than or equal to (>=) 30% decrease in the sum of the diameters of all index lesions; or stable disease [SD], less than (<) 30% decrease in sum of longest diameters of all index lesions with duration of at least 16 weeks).
4. Progression-Free Survival (PFS) [ Time Frame: From randomization to the date of first documented evidence of PD (an expected average of 3 years) ]
   PFS is defined as the duration from the date of randomization to the date of objectively documented progression or death due to any cause, whichever status is recorded first.
5. Overall Survival (OS) [ Time Frame: From randomization to the date of first documented evidence of PD (an expected average of 3 years) ]
   Overall Survival is defined as the duration from the date of randomization to the date of death due to any cause.
6. Maximum Observed Analyte Concentration (Cmax) of Daratumumab [ Time Frame: Predose and end of infusion Cycle 1 Day 1(C1D1), Predose-C2D1, C3D1, C3D15, end of infusion-C3D15; predose and end of infusion-C4D1, predose and end of infusion-C8D1; predose-C12D1, C16D1 up to end of treatment (30 days after the last dose) ]
   Maximum observed analyte concentration of daratumumab will be assessed.
7. Maximum Observed Analyte Concentration (Cmax) of Atezolizumab [ Time Frame: Predose and end of infusion-C1D1, end of infusion - C1D2, predose - C2D1, C3D1 ; pre-dose and end of infusion-C4D1, pre-dose and end of infusion-C8D1; predose-C12D1, C16D1 up to end of treatment (30 days after the last dose) ]
   Maximum observed analyte concentration of atezolizumab will be assessed.
8. Minimum Observed Analyte Concentration (Cmin) of Daratumumab [ Time Frame: Predose and end of infusion Cycle 1 Day 1(C1D1), Predose-C2D1, C3D1, C3D15, end of infusion-C3D15; predose and end of infusion-C4D1, predose and end of infusion-C8 D1; predose-C12D1, C16D1 up to end of treatment (30 days after the last dose) ]
   Minimum observed analyte concentration of daratumumab will be assessed.
9. Minimum Observed Analyte Concentration (Cmin) of Atezolizumab [ Time Frame: Predose and end of infusion-C1D1, end of infusion - C1D2, predose - C2D1, C3D1 ; pre-dose and end of infusion-C4D1, pre-dose and end of infusion-C8D1; predose-C12D1, C16D1 up to end of treatment (30 days after the last dose) ]
   Minimum observed analyte concentration of atezolizumab will be assessed.
10. Anti-Daratumumab Antibodies Concentration [ Time Frame: predose - C1D1, C2D1, C8D1, C12D1, C16D1 up to end of treatment (30 days after the last dose) ]
11. Anti-Atezolizumab Antibodies Concentration [ Time Frame: predose - C1D1, C2D1, C3D1, C4D1, C8D1, C12D1, C16D1 up to end of treatment (30 days after the last dose) ]
12. Number of Participants with Anti-Recombinant Human Hyaluronidase PH20 (rHuPH20) Antibodies [ Time Frame: Predose - C1D1, C2D1, C8D1, C12D1, C16D1 up to end of treatment (8 weeks after the last dose) ]
    Number of participants with anti-rHuPH20 antibodies will be reported. Plasma samples will be collected for determination of antibodies binding to rHuPH20.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
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 as determined by an immunohistochemistry (IHC) assay performed by the central laboratory on tissue obtained after the last line of therapy:

  1. Randomized phase of the study

     a) Participants with a tumor cell PD-L1 score of TC1-3 who are anti-PD-1 or anti-PD-L1 treatment naïve will be eligible for screening

  2. Phase 1b (Dara-subcutaneous [SC]+ atezolizumab cohort)

     1. Participants with a tumor cell PD-L1 score of TC0 who are anti-PD-1 or anti-PD-L1 treatment naïve will be eligible for screening
     2. Participants who have disease progression on or after anti-PD-1 or anti-PD-L1 therapy and with any tumor cell PD-L1 score (TC0-3) will be eligible for screening
• 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. Randomized Phase: Anti-CD38 therapy (including daratumumab), CD137 agonists, and immune checkpoint inhibitors including but not limited to anti-CTLA 4, anti PD-1, and anti-PD-L1 therapies
  2. Phase 1b (Dara-SC + atezolizumab cohort): Anti-CD38 therapy (including daratumumab), CD137 agonists, and immune checkpoint inhibitors with exception of anti-PD-1 or anti-PD-L1 agents
• 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

Contacts and Locations

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Contacts

Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:		JNJ.CT@sylogent.com

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Sponsors and Collaborators

Janssen Research & Development, LLC

Genentech, Inc.

Investigators

Study Director:	Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC

More Information

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Additional Information:

To learn how to participate in this trial please click here. 

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
Last Update Posted:	May 25, 2018
Last Verified:	May 2018

Studies a U.S. FDA-regulated Device Product:		No

Additional relevant 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