Clinical Trials /

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

NCT02709889

Description:

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:

Active, not recruiting

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

Trial 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

Trial Interventions

DrugSynonymsArms
Rovalpituzumab tesirineSC16LD6.5Rovalpituzumab tesirine

Trial Purpose

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 (GEP), neuroendocrine carcinoma (NEC), other NEC, and solid tumors other than the above.

Trial Arms

NameTypeDescriptionInterventions
Rovalpituzumab tesirineExperimentalRovalpituzumab tesirine 0.2-0.4 mg/kg will be administered intravenously on Day 1 of each 6-week cycle.
  • Rovalpituzumab tesirine

Eligibility Criteria

Inclusion Criteria:

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

- Measurable disease as defined by RECIST 1.1

- 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-PD-1, anti-PD-L1, or anti-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 (see Appendix 12.4) 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 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.

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:N/A
Minimum Eligible Age:N/A
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:1 year
Safety Issue:No
Description:

Secondary Outcome Measures

Measure:Objective response rate
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 48 months.
Safety Issue:No
Description:
Measure:Duration of response
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 48 months.
Safety Issue:No
Description:
Measure:Progression free survival
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 48 months.
Safety Issue:No
Description:
Measure:Overall survival
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 48 months.
Safety Issue:No
Description:
Measure:Clinical benefit rate
Time Frame:Baseline, every 6 weeks until 6 months, then every 12 weeks until disease progression, assessed up to 48 months.
Safety Issue:No
Description:
Measure:Maximum Plasma Concentration (Cmax)
Time Frame:Cycles 1, 2 and 4: day 1 (pre-dose, 30 min post-dose, 6 hours post-dose), 3, 8, 15, 29; Cycles 3, 5 and above: day 1, 8, 15, 29; up to 1 year.
Safety Issue:No
Description:
Measure:Area Under the Curve (AUC)
Time Frame:Cycles 1, 2 and 4: day 1 (pre-dose, 30 min post-dose, 6 hours post-dose), 3, 8, 15, 29; Cycles 3, 5 and above: day 1, 8, 15, 29; up to 1 year.
Safety Issue:No
Description:
Measure:Anti-therapeutic Antibodies (ATA)
Time Frame:Cycles 1, 2 and 4: day 1 (pre-dose, 30 min post-dose, 6 hours post-dose), 3, 8, 15, 29; Cycles 3, 5 and above: day 1, 8, 15, 29; up to 1 year.
Safety Issue:No
Description:

Trial Keywords