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

September 21, 2020 updated by: AbbVie

An Open-Label Study of Rovalpituzumab Tesirine in Subjects With Delta-Like Protein 3-Expressing Advanced Solid Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Ctr /ID# 155424
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic - Scottsdale /ID# 155419
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles /ID# 155429
      • San Francisco, California, United States, 94143-2204
        • Univ California, San Francisco /ID# 155409
      • West Hollywood, California, United States, 90048
        • Cedars-Sinai Medical Center - West Hollywood /ID# 155428
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Univ of Colorado Cancer Center /ID# 155415
      • Denver, Colorado, United States, 80218
        • Sarah Cannon Research Institute at HealthONE - Denver /ID# 155420
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida - Archer /ID# 155414
      • Tampa, Florida, United States, 33612-9416
        • Moffitt Cancer Center /ID# 170220
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital /ID# 155417
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky Chandler Medical Center /ID# 155423
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University /ID# 155412
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital /ID# 155411
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute /ID# 171044
    • Minnesota
      • Rochester, Minnesota, United States, 55905-0001
        • Mayo Clinic - Rochester /ID# 155416
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University-School of Medicine /ID# 155425
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of NJ /ID# 162010
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico /ID# 205054
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Comprehensive Cancer Center /ID# 162015
      • New York, New York, United States, 10021
        • Weill Cornell Medical College /ID# 155418
    • North Carolina
      • Durham, North Carolina, United States, 27710-3000
        • Duke University Medical Center /ID# 155421
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Univ Hosp Cleveland /ID# 155410
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University /ID# 162011
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Greenville Hospital System /ID# 155427
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research /ID# 162014
      • Fort Worth, Texas, United States, 76104-2150
        • Texas Oncology - Forth Worth /ID# 162045
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center /ID# 155413
    • Utah
      • Salt Lake City, Utah, United States, 84112-5500
        • University of Utah /ID# 155426
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists /ID# 162006
    • Washington
      • Vancouver, Washington, United States, 98684
        • Northwest Cancer Specialists, P.C. /ID# 155431

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Rovalpituzumab Tesirine
Rovalpituzumab 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.
Drug: Rovalpituzumab tesirine
Other Names:
  • SC16LD6.5
Drug: Dexamethasone
Dexamethasone will be provided through a participant's local prescription by Investigator or other provider (i.e., dexamethasone will not be provided by the Sponsor).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
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.
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).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
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.
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
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.
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).
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
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.
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.
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
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.
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.
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
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.
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.
Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 35.2 months.
Serum Concentrations of Rovalpituzumab Tesirine Over Time
Time Frame: Cycle 1: 0, 0.5, 6, 48, 168, 336, 672 hours postdose
Cycle 1: 0, 0.5, 6, 48, 168, 336, 672 hours postdose
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).
Number of participants treated across each dose level reported to potentially have ATAs against rovalpituzumab tesirine at any time during the study.
Day 1 and 42 days after last dose. The overall mean number of 6-week treatment cycles was 1 (range 1.0, 5.0).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AbbVie

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 23, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 27, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 27, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 2, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 16, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 19, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SCRX001-006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Time Frame

Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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