Rovalpituzumab Tesirine (SC16LD6.5) in Recurrent Small Cell Lung Cancer

Phase 1

Completed

Conditions: Recurrent Small Cell Lung Cancer

Interventions: Drug: Rovalpituzumab tesirine (SC16LD6.5)

Registration Number: NCT01901653

Lead Sponsor: Stemcentrx

Brief Summary: The purpose of this study is to assess the safety and tolerability of rovalpituzumab tesirine (SC16LD6.5) at different dose levels in patients with small cell lung cancer whose cancer has progressed or recurred following standard chemotherapy. Once a safe and tolerable dose is determined, the anti-cancer activity of SC16LD6.5 will be assessed by measuring the extent of tumor shrinkage. SC16LD6.5 is an antibody-drug conjugate (ADC). The antibody (SC16) targets a protein that appears to be expressed on the surface of most small cell lung cancers that have been assessed using an immunohistochemical assay. The drug, D6.5, is a very potent form of chemotherapy, specifically a DNA-damaging agent, that is cell cycle independent. ADC's theoretically provide more precise delivery of chemotherapy to cancer cells, possibly improving effectiveness relative to toxicities.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 82

Inclusion Criteria

Not provided

Exclusion Criteria

Patients who are pregnant or breastfeeding.
Active involvement of the Central Nervous System (CNS).
Uncontrolled infection or systemic disease.
Clinically significant cardiac disease not well controlled with medication (e.g., congestive heart failure, symptomatic coronary artery disease e.g. angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months.
Chemotherapy regimens within the last 21 days (or within 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens, biologic, and targeted therapy given continuously or on a weekly basis with limited potential for delayed toxicity within the last 14 days.
No concurrent systemic chemotherapy or anticancer biologic therapy is allowed. Note: Patients on hormonal treatment for breast cancer or prostate cancer may continue on treatment and enter into study.
Known hypersensitivity to any components of SC16LD6.5 study drug product.
Patients with known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both), a history of solid organ or bone marrow transplantation would generally be considered to have met exclusion criteria, however exceptions may be considered on a case-by-case basis by the medical monitor.
Psychiatric disorder or social or geographic situation that would preclude study participation.
QT interval measurement corrected by Fridericia's formula (QTcF) interval of >450 msec (males) or >470 msec (females)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rovalpituzumab tesirine	Rovalpituzumab tesirine (SC16LD6.5)	Rovalpituzumab tesirine will be administered as a single agent, at increasing dose levels as permitted based on real-time assessment of safety and tolerability, intravenously over 30 minutes. Doses will be repeated on Day 1 of each 21-day or 42-day cycle until either unacceptable toxicity or evidence of disease progression occurs.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of Rovalpituzumab Tesirine	The DLT period was defined as either 21 or 42 days following the first dose of Rovalpituzumab tesirine during dose escalation (Phase 1a), depending on Cycle length.	MTD was determined by testing increasing doses from 0.05 mg/kg up to 0.8 mg/kg on Day 1 of every 21-day or 42-day cycle, Phase 1a cohorts 1 to 8. MTD will be defined as the dose level immediately below the dose level at which ≥ 2 of the first 3 subjects per cohort (or ≥ 2 of 6 subjects) during the first cycle experience a study drug related dose limiting toxicity (DLT).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	From first dose of rovalpituzumab tesirine to last event, up through study completion (on average approximately 4 months).	Overall response was assessed at each visit post-baseline based on a subject's lesion measurements or assessments (complete response \[CR\], partial response \[PR\], stable disease \[SD\], progressive disease \[PD\], or not evaluable as defined by RECIST v1.1, plus an additional category of early death). The best overall response was then determined. A subject was defined as having an objective response if they had a best overall response of CR or PR prior to receiving any subsequent anticancer therapy; confirmed response is confirmation of CR or PR at least 4 weeks from the initial determination per RECIST v1.1. Subjects with a post-baseline assessment were included in the calculations for objective response rate (ORR). Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).
Clinical Benefit Rate (CBR)	From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on avergae approximately 4 months).	Clinical Benefit is defined as a subject with best Overall Response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) prior to receiving any subsequent anticancer therapy; as defined by RECIST version 1.1. CBR is defined as the proportion of subjects with Clinical Benefit based on assessment of overall response. CBR will be presented as a number and percentage with 95% confidence bounds. Any subjects not exhibiting a response (CR or PR or SD) are considered non-responders. Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).
Duration of Response (DOR)	From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on average approximately 4 months, but up to 6.51 months).	Duration of response (DOR) was defined as the number of months from the initial CR or PR to the time of disease progression or death, whichever occurred first. Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).
Overall Survival	From first dose of Rovalpituzumab tesirine to last event, up through study completion (on average approximately 5-7 months, but up to 14.6 months).	Overall survival (OS) was defined as the time from the first day of study treatment to death. Subjects who were alive were censored at the date of last known alive.
Progression-free Survival (PFS)	From first dose of rovalpituzumab tesirine to last event timepoint, up through study completion (approximately 4 months on average, but up to 14.46 months).	Progression-free survival (PFS) was defined as the number of months from the first day of study drug administration to disease recurrence or progression, or death on study. Outcome is based on data reported by Investigator (INV); available and evaluable radiographic scans were collected retrospectively for review by an Independent Review Committee (IRC).
Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)	From Day 1 of first dose to End of Dose Cycle	The maximum serum concentration (Cmax; measured in μg/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing cycle.
Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC	From Day 1 of first dose to End of Dose Cycle	The area under the serum concentration-time curve (AUC; measured in μg•d/mL) is a method of measurement to determine the total exposure of a drug in blood serum.

Trial Locations

Locations (8): University of Alabama at Birmingham
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Birmingham, Alabama, United States
Florida Cancer Specialists
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Sarasota, Florida, United States
University of Chicago Medical Center
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Chicago, Illinois, United States
Memorial Sloan Kettering Cancer Center
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New York, New York, United States
Duke University Medical Center
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Durham, North Carolina, United States
Tennessee Oncology
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Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
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Houston, Texas, United States
Blue Ridge Cancer Care
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Roanoke, Virginia, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States