Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Recurrence

Small Cell Lung Carcinoma

Lung Neoplasms

Carcinoma

Disease Attributes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

All Drugs and Chemicals

Rovalpituzumab tesirine

Immunoconjugates

Immunologic Factors

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.

Rovalpituzumab tesirine (SC16LD6.5)

Donald Strickland, MD

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.

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

Phase I/II Open Label Dose Escalation Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of SC16LD6.5 as a Single Agent in Patients With Recurrent Small Cell Lung Cancer

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).

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).

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).

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).

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).

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.

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.

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.

Stemcentrx

SCLC Subjects: Rovalpituzumab tesirine 0.05 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 1 (SCLC)

SCLC Subjects: Rovalpituzumab tesirine 0.1 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 2 (SCLC)

SCLC Subjects: Rovalpituzumab tesirine 0.2 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 3 (SCLC)

SCLC Subjects: Rovalpituzumab tesirine 0.4 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 4 (SCLC)

SCLC Subjects: Rovalpituzumab tesirine 0.8 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 5 (SCLC)

SCLC Subjects: Rovalpituzumab tesirine 0.4 mg/kg on Day 1 of every 42-day cycle

Phase 1a: Cohort 6 (SCLC)

SCLC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle

Phase 1a: Cohort 7 (SCLC)

Phase 1a: Cohort 8 (SCLC)

LCNEC Subjects: Rovalpituzumab tesirine 0.2 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 8 (LCNEC)

SCLC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles; if eligible, retreatment with rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles. Ongoing subjects from Phase 1a who received an initial dose of 0.2 mg/kg on Day 1 of each 21-day cycle for 3 cycles, and if eligible, retreatment with rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles.

Phase 1b: Retreatment (SCLC)

LCNEC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles; if eligible, retreatment with rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles. Ongoing subjects from Phase 1a who received an initial dose of 0.2 mg/kg on Day 1 of each 21-day cycle for 3 cycles, and if eligible, retreatment with rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles.

Phase 1b: Retreatment (LCNEC)

SCLC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles; followed by maintenance with rovalpituzumab tesirine 0.1 mg/kg on Day 1 of every 42-day cycle

Phase 1b: Maintenance (SCLC)

LCNEC Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle for 2 cycles; followed by maintenance with rovalpituzumab tesirine 0.1 mg/kg on Day 1 of every 42-day cycle

Phase 1b: Maintenance (LCNEC)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

ECOGScale:Score-Description:0-Normalactivity.Fullyactive,abletocarryonallprediseaseperformancew/orestriction/1-Symptoms,but ambulatory.Restrictedinphysicallystrenuousactivity,butambulatoryandabletocarryoutworkofa light/sedentarynature(eg,light housework,office work)/2-In bed\<50%ofthetime.Ambulatoryandcapableofallselfcare,but unabletocarryoutanyworkactivities.Upandabout\>50%ofwakinghours/3-In bed\>50%ofthetime.Capableofonlylimitedselfcare,confinedtobed/chair\>50%ofwakinghours/4-100% bedridden.Completelydisabled.Cannotcarryonanyselfcare.Totallyconfinedtobed/chair/5-Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Senior Director, Clinical Operations

Rovalpituzumab tesirine (SC16LD6.5) will be administered intravenously (IV) to subjects with recurrent small cell lung cancer. Rovalpituzumab tesirine will be given on Day 1 of every 21-day or 42-day cycle.

Rovalpituzumab Tesirine

All subjects from Phase 1a Dose Escalation: Cohort 1 to 8 who received at least 1 dose of study drug.

Maximum Tolerated Dose (MTD) of Rovalpituzumab Tesirine

ORR unconfirmed by Investigator

ORR confirmed by Investigator

ORR unconfirmed by IRC

ORR confirmed by IRC

SCLC Subjects who received rovalpituzumab tesirine 0.2 mg/kg to 0.4 mg/kg

SCLC Subjects

LCNEC Subjects who received rovalpituzumab tesirine 0.2 mg/kg to 0.4 mg/kg

LCNEC Subjects

Subjects with at least one post-dose assessment. All LCNEC subjects were analyzed. No LCNEC subjects achieved CR or PR and, therefore, the ORR was 0%.

Objective Response Rate (ORR)

DOR by INV

DOR by IRC

Subjects with at least one post-dose assessment. No LCNEC subjects achieved CR or PR, therefore DOR was not analyzed.

Duration of Response (DOR)

CBR unconfirmed by INV

CBR confirmed by INV

CBR unconfirmed by IRC

CBR confirmed by IRC

Subjects with at least one post-dose assessment.

Clinical Benefit Rate (CBR)

PFS by INV

PFS by IRC

Progression-free Survival (PFS)

Overall Survival

All Subjects: Rovalpituzumab tesirine 0.05 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 1

All Subjects: Rovalpituzumab tesirine 0.1 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 2

All Subjects: Rovalpituzumab tesirine 0.2 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 3

All Subjects: Rovalpituzumab tesirine 0.4 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 4

All Subjects: Rovalpituzumab tesirine 0.8 mg/kg on Day 1 of every 21-day cycle

Phase 1a: Cohort 5

All Subjects: Rovalpituzumab tesirine 0.4 mg/kg on Day 1 of every 42-day cycle

Phase 1a: Cohort 6

All Subjects: Rovalpituzumab tesirine 0.3 mg/kg on Day 1 of every 42-day cycle

Phase 1a: Cohort 7

Phase 1a: Cohort 8

All subjects who received at least 1 dose of study drug, with evaluable data at each given timepoint. For Phase 1b, pharmacokinetic (PK) sampling was sparse; therefore, pharmacokinetic parameters were not estimated.

Spots Global Cancer Trial Database for Rovalpituzumab Tesirine (SC16LD6.5) in Recurrent Small Cell Lung Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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