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Study of Rovalpituzumab Tesirine (SC16LD6.5) for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY)

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ClinicalTrials.gov Identifier: NCT02674568
Recruitment Status : Completed
First Posted : February 4, 2016
Results First Posted : October 23, 2019
Last Update Posted : July 7, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE January 29, 2016
First Posted Date  ICMJE February 4, 2016
Results First Submitted Date  ICMJE September 30, 2019
Results First Posted Date  ICMJE October 23, 2019
Last Update Posted Date July 7, 2020
Actual Study Start Date  ICMJE January 25, 2016
Actual Primary Completion Date October 19, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 30, 2019)
  • Objective Response Rate [ Time Frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks ]
    Objective response is defined as a participant with the best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1, prior to receiving any subsequent anticancer therapy and retreatment, and is confirmed by a consecutive response assessment at least 4 weeks (28 days) from the initial determination of CR/PR. Analyzed based on response assessments from both the Independent Review Committee (IRC) and investigators. CR: disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
  • Overall Survival [ Time Frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks ]
    Overall survival is defined as the time from the first dose date to death for any reason. Participants who were alive at the clinical data cut-off were censored at the last known alive date. Based on Kaplan-Meier estimates.
Original Primary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
  • Objective Response Rate [ Time Frame: 1.5 year ]
  • Overall survival for subjects [ Time Frame: 4 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2019)
  • Overall Response Rate [ Time Frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks ]
    Overall response rate is defined as the percentage of participants with a response of CR or PR, regardless of confirmation, per RECIST v 1.1 prior to receiving any subsequent anticancer therapy and retreatment. Any participants not exhibiting a response (CR or PR) as defined above were considered non-responders. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
  • Duration of Objective Response [ Time Frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks ]
    Duration of objective response is defined as the time from the date of first documented CR or PR of participants with a confirmed response to the documented date of progressive disease (PD) or death, whichever occurred first. Participants who neither progressed nor died are censored at the last evaluable disease assessment. Analyzed based on response assessments from both the IRC and investigators. Based on Kaplan-Meier estimates. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.)
  • Progression-Free Survival [ Time Frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks ]
    Progression-free survival is defined as the time from the first dose date to the documented date of PD or death, whichever occurred first. Participants who neither progressed nor died were censored at the last evaluable disease assessment. Analyzed based on response assessments from both the IRC and investigators. Based on Kaplan-Meier estimates. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.)
  • Clinical Benefit Rate [ Time Frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks ]
    Clinical benefit rate is defined as the percentage of participants with an overall response of CR or PR or stable disease (SD) with SD of a minimum duration of 42 days from the first dose date. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. (The appearance of one or more new lesions is also considered progression.)
  • Duration of Clinical Benefit [ Time Frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks ]
    Duration of clinical benefit is defined as time from the date of first documented CR or PR or SD of ≥ 42 days from first dose date (-7 days to allow for scheduled visit window per the protocol) to the documented date PD or death, whichever occurs first. Analyzed based on response assessments from both the IRC and investigators. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
  • Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit [ Time Frame: Cycle 1: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29. Cycle 2: Day 1, 30 minutes pre-infusion; Day 1, 30 minutes post-infusion; Day 3; Day 15; Day 29; End of Treatment (up to Day 29). ]
  • Number of Anti-Therapeutic Antibody (ATA) Positive Participants [ Time Frame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks ]
  • Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment [ Time Frame: From first dose of study drug through the end of the initial treatment period (84 ± 6 days) ]
    An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose: is fatal or life-threatening; results in death or hospitalization; is disabling/incapacitating or a congenital anomaly/birth defect; is medically significant. AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03 terminology: grade 1=mild; grade 2=moderate; grade 3=severe; grade 4 life-threatening; grade 5=death. TEAEs were defined as AEs that were newly occurring or worsened following study treatment.
  • Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment [ Time Frame: From first dose of study drug through the end of the initial treatment period (84 ± 6 days) ]
    TEAEs were defined as AEs that were newly occurring or worsened following study treatment.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
  • Clinical Benefit Rate [ Time Frame: 4 years ]
  • Duration of Response [ Time Frame: 4 years ]
  • Progression-free Survival [ Time Frame: 4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: February 3, 2016)
  • Number of subjects with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 4 years ]
  • Number of subjects with treatment-related changes in vital signs from baseline [ Time Frame: 4 years ]
  • Number of subjects with treatment-related laboratory abnormalities from baseline [ Time Frame: 4 years ]
  • Number of subjects with treatment-related electrocardiographic intervals change from baseline [ Time Frame: 4 years ]
  • Number of subjects with treatment-related electrocardiography parameters change from baseline [ Time Frame: 4 years ]
 
Descriptive Information
Brief Title  ICMJE Study of Rovalpituzumab Tesirine (SC16LD6.5) for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer
Official Title  ICMJE An Open-label, Single-Arm, Phase 2 Study Evaluating the Efficacy, Safety and Pharmacokinetics of Rovalpituzumab Tesirine (SC16LD6.5) for Third-line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY)
Brief Summary The purpose of this study is to determine the efficacy of rovalpituzumab tesirine as a third-line and later treatment for participants with relapsed or refractory delta-like protein 3 (DLL3) expressing small cell lung cancer (SCLC).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Small Cell Lung Cancer
Intervention  ICMJE Drug: Rovalpituzumab tesirine
Rovalpituzumab tesirine is a DLL3 targeted antibody drug conjugate (ADC).
Other Name: SC16LD6.5
Study Arms  ICMJE Experimental: Rovalpituzumab Tesirine
0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible participants.
Intervention: Drug: Rovalpituzumab tesirine
Publications * Morgensztern D, Besse B, Greillier L, Santana-Davila R, Ready N, Hann CL, Glisson BS, Farago AF, Dowlati A, Rudin CM, Le Moulec S, Lally S, Yalamanchili S, Wolf J, Govindan R, Carbone DP. Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study. Clin Cancer Res. 2019 Dec 1;25(23):6958-6966. doi: 10.1158/1078-0432.CCR-19-1133. Epub 2019 Sep 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 30, 2019)
342
Original Estimated Enrollment  ICMJE
 (submitted: February 3, 2016)
154
Actual Study Completion Date  ICMJE October 19, 2018
Actual Primary Completion Date October 19, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Adult aged 18 years or older
  2. Histologically confirmed SCLC with documented disease progression after at least 2 prior systemic regimens, including at least one platinum-based regimen
  3. DLL3-expressing SCLC based on central immunohistochemistry (IHC) assessment of banked or otherwise representative tumor tissue. Positive is defined as staining in ≥ 1% of tumor cells
  4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  6. Minimum life expectancy of at least 12 weeks
  7. Subjects with a history of central nervous system (CNS) metastases must have documentation of stable or improved status based on brain imaging for at least 2 weeks after completion of definitive treatment and within 2 weeks prior to first dose of study drug, off or on a stable dose of corticosteroids
  8. Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior to initiation of study drug administration
  9. Adequate hematologic and organ function as confirmed by laboratory values
  10. Last dose of any prior therapy administered by the following time intervals before the first dose of study drug:

    • Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks
    • Immune-checkpoint inhibitors (i.e., anti-PD-1, anti-PD-L1, or anti-CTLA-4): 4 weeks
    • Other monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies: 4 weeks (2 weeks with documented disease progression)
  11. Females of childbearing potential must have a negative beta human chorionic gonadotropin (β-hCG) pregnancy test result within 7 days prior to the first dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.

Exclusion Criteria:

  1. Any significant medical condition, including any suggested by screening laboratory findings that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 6 months) or neurological disorder (e.g., seizure disorder active within 6 months)
  2. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to their first dose of study drug
  3. Recent or ongoing serious infection, including:

    • Any active grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03) viral, bacterial, or fungal infection within 2 weeks of the first dose of the study drug. Routine antimicrobial prophylaxis is permitted.
    • Known seropositivity for or active infection by human immunodeficiency virus (HIV)
    • Active Hepatitis B (by surface antigen expression or polymerase chain reaction) or C (by polymerase chain reaction) infection or on hepatitis-related antiviral therapy within 6 months of first dose of study drug.
  4. Women who are breastfeeding
  5. Systemic therapy with corticosteroids at >20 mg/day prednisone or equivalent within 1 week prior to the first dose of study drug
  6. History of another invasive malignancy that has not been in remission for at least 3 years. Exceptions to the 3 year limit include nonmelanoma skin cancer, curatively treated localized prostate cancer, and cervical cancer in situ on biopsy or squamous intraepithelial lesion on pap smear
  7. Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, or known hypersensitivity to rovalpituzumab tesirine or excipient contained in the drug formulation, unless undergoing retreatment with rovalpituzumab tesirine in the context of this protocol
Sex/Gender  ICMJE Not Provided
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries France,   Germany,   Hungary,   Poland,   Spain,   United States
 
Administrative Information
NCT Number  ICMJE NCT02674568
Other Study ID Numbers  ICMJE SCRX001-002
2015-004506-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP