Clinical Trials /

Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors

NCT02709889

Description:

The primary objective of this study is to assess the safety and tolerability of rovalpituzumab tesirine in subjects with specific delta-like protein 3-expressing advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors
  • Official Title: An Open-Label Study of Rovalpituzumab Tesirine in Subjects With Delta-Like Protein 3-Expressing Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: SCRX001-006
  • NCT ID: NCT02709889

Conditions

  • Malignant Melanoma
  • Medullary Thyroid Cancer
  • Glioblastoma
  • Large-Cell Neuroendocrine Carcinoma
  • Neuroendocrine Prostate Cancer
  • High Grade Gastroenteropancreatic Neuroendocrine Carcinoma
  • Other Neuroendocrine Carcinoma
  • Other Solid Tumors

Interventions

DrugSynonymsArms
Rovalpituzumab tesirineSC16LD6.5Rovalpituzumab Tesirine
DexamethasoneRovalpituzumab Tesirine

Purpose

The primary objective of this study is to assess the safety and tolerability of rovalpituzumab tesirine in subjects with specific delta-like protein 3-expressing advanced solid tumors.

Detailed Description

      This is a multicenter, open-label study involving multiple specific advanced solid tumor
      types, consisting of a dose escalation part A followed by an expansion part B. Cancer
      subtypes will be studied in separate disease-specific cohorts in both Parts. Eight separate
      cohorts will enroll malignant melanoma, medullary thyroid cancer (MTC), glioblastoma, large
      cell neuroendocrine carcinoma (LCNEC), neuroendocrine prostate cancer (NEPC), high-grade
      gastroenteropancreatic neuroendocrine carcinoma (GEP NEC), other NEC, and solid tumors other
      than the above.
    

Trial Arms

NameTypeDescriptionInterventions
Rovalpituzumab TesirineExperimentalRovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
  • Rovalpituzumab tesirine
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed, unresectable advanced solid malignancy with documented
             disease progression after at least 1 prior systemic therapy

          -  Disease is relapsed/refractory to prior standard systemic therapy or for which
             standard or curative therapy does not exist or is not considered appropriate by the
             Investigator.

          -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
             1.1

          -  Delta-like protein 3 (DLL3)-expressing malignancy based on central immunohistochemical
             (IHC) testing of representative baseline tumor tissue (archived tissue or on-study
             biopsy). Positive is defined as staining in ≥ 1% of tumor cells.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Minimum life expectancy of at least 12 weeks

          -  Subjects with a history of central nervous system (CNS) metastases must have
             documentation of stable or improved 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. Definitive treatment may include
             surgical resection, whole brain irradiation, and/or stereotactic radiation therapy.
             (Applicable to tumor types of non-CNS primary origin only)

          -  Recovery to Grade 1 of any clinically significant toxicity (excluding alopecia) prior
             to initiation of study drug administration

          -  Adequate hematologic and organ function as confirmed by laboratory values

          -  Last dose of any prior therapy administered by the following time intervals before the
             first dose of study drug:

               1. Chemotherapy, small molecule inhibitors, radiation, and/or other investigational
                  anticancer agents (excluding investigational monoclonal antibodies): 2 weeks.

               2. Immune-checkpoint inhibitors (e.g., anti-programmed death protein 1 [PD-1],
                  anti-programmed death-ligand 1 [PD-L1], or anti-cytotoxic T-lymphocyte-associated
                  protein 4 [CTLA-4]), monoclonal antibodies, antibody-drug conjugates,
                  radioimmunoconjugates, or T-cell or other cell-based therapies: 4 weeks (2 weeks
                  with documented disease progression).

          -  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:

          -  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 3 months) or
             neurological disorder (e.g., seizure disorder active within 3 months).

          -  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.

          -  Recent or ongoing serious infection, including:

               1. Any active grade 3 or higher (per National Cancer Institute Common Terminology
                  Criteria for Adverse Events version [NCI CTCAE] 4.03) viral, bacterial, or fungal
                  infection within 2 weeks of the first dose of the study drug. Routine
                  antimicrobial prophylaxis is permitted.

               2. Known seropositivity for or active infection by human immunodeficiency virus
                  (HIV).

               3. 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.

          -  Women who are pregnant or breastfeeding

          -  Systemic therapy with corticosteroids at >20 mg/day prednisone or equivalent within 1
             week prior to the first dose of study drug

          -  History of another invasive malignancy that has not been in remission for at least 3
             years. Exceptions to the 3year limit include non-melanoma skin cancer, curatively
             treated localized prostate cancer, ductal carcinoma in situ, and cervical cancer in
             situ on biopsy or squamous intraepithelial lesion on pap smear.

          -  Prior exposure to a pyrrolobenzodiazepine (PBD)-based drug, prior participation in a
             rovalpituzumab tesirine clinical trial, 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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Summary of Treatment-Emergent Adverse Events (TEAEs), by Dose and Neuroendocrine (NEC) or Non-NEC Disease Groups
Time Frame:From first dose of study drug through 30 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).
Safety Issue:
Description:The number of participants with TEAEs, serious TEAEs, study drug-related TEAEs, and study drug discontinuations or dose reductions due to TEAEs, summarized by dose received and neuroendocrine (NEC) or non-NEC disease groups. 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.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Safety Issue:
Description:ORR is defined as percentage of participants whose best overall response was either complete response (CR) or partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: A ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measure:Clinical Benefit Rate (CBR)
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Safety Issue:
Description:CBR is defined as the percentage of participants with best overall response (confirmed or unconfirmed) of CR, PR or stable disease (SD) per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: 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 progressed disease (PD), taking as reference the smallest sum diameters while on study. SD criteria must have met at least once after study entry at a minimum interval of 42 days (-7 days to allow for scheduled visit window per the protocol).
Measure:Duration of Response (DOR)
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Safety Issue:
Description:DOR is defined as the time from the first assessment on therapy of a CR or PR response (per RECIST v1.1) to the date of progressive disease or death. CR: Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: A ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not have progression were censored at the last non-missing response assessment on-therapy or baseline. Based on Kaplan-Meier estimates.
Measure:Progression Free Survival (PFS)
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Safety Issue:
Description:PFS is defined as the time from the first dose date to the date of disease progression or death. Participants who did not have progression or death are censored at the last non-missing response assessment on-therapy or baseline. Based on Kaplan-Meier estimates.
Measure:Overall Survival (OS)
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Safety Issue:
Description:Overall survival is defined as the time from the first dose date to death for any reason. Subjects who were alive at the clinical data cut-off are censored at the last known alive date. Based on Kaplan-Meier estimates.
Measure:Serum Concentrations of Rovalpituzumab Tesirine Over Time
Time Frame:Cycle 1: 0, 0.5, 6, 48, 168, 336, 672 hours postdose
Safety Issue:
Description:
Measure:Number of Participants With Anti-therapeutic Antibodies (ATA)
Time Frame:Day 1 and 42 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).
Safety Issue:
Description:Number of participants treated across each dose level reported to potentially have ATAs against rovalpituzumab tesirine at any time during the study.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:AbbVie

Last Updated

October 19, 2020