Clinical trial NCT02674568: 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: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Keywords: SCLC
Small Cell Lung Cancer
DLL#
Relapsed
Refractory
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-02-04
Enrollment: 342
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate
timeFrame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
measure: Overall Survival
timeFrame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
Secondary outcomes:
measure: Overall Response Rate
timeFrame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
measure: Duration of Objective Response
timeFrame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
measure: Progression-Free Survival
timeFrame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
measure: Clinical Benefit Rate
timeFrame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
measure: Duration of Clinical Benefit
timeFrame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
measure: Rovalpituzumab Tesirine Antibody-Drug Conjugate Plasma Concentrations by Study Visit
timeFrame: 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).
measure: Number of Anti-Therapeutic Antibody (ATA) Positive Participants
timeFrame: up to 122.4 weeks; mean (SD) duration of follow-up was 29.0 (23.77) weeks
measure: Number of Participants With Treatment-Related Adverse Events (TEAEs) During Initial Treatment
timeFrame: From first dose of study drug through the end of the initial treatment period (84 ± 6 days)
measure: Number of Participants With TEAEs Occurring in at Least 10% of All Participants During Initial Treatment
timeFrame: From first dose of study drug through the end of the initial treatment period (84 ± 6 days)
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.