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

NCT01901653 | Completed Phase 1 Results

• 1 other identifier: SCRX16-001
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 8

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.

Conditions

Recurrent Small Cell Lung Cancer

Keywords

Small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Rovalpituzumab Tesirine

  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).

  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.

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  From first dose of rovalpituzumab tesirine to last event, up through study completion (on average approximately 4 months).

• 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).

• Clinical Benefit Rate (CBR)

  From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on avergae approximately 4 months).

• 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).

• 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).

Study Arms (1)

Rovalpituzumab tesirine

EXPERIMENTAL

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.

Drug: Rovalpituzumab tesirine (SC16LD6.5)

Interventions

Rovalpituzumab tesirine (SC16LD6.5) DRUG

Rovalpituzumab tesirine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent
• Male or female ≥18 years of age
• Histologic or cytologic confirmed diagnosis of small cell lung cancer, either limited or extensive disease at initial presentation is allowed
• Evidence of progressive disease during or following 1 or 2 prior chemotherapy regimens
• At least 1 prior regimen must have contained a platinum salt
• 'Adjuvant therapy' will constitute a prior treatment regimen
• No more than 2 prior regimens are allowed
• Measurable disease (only for the phase II portion)
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-1
• A minimum life expectancy of 12 weeks
• Adequate bone marrow, hepatic and renal function as evidenced by:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• Serum bilirubin \< 1.5 x ULN

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Stemcentrx: lead

Study Sites (8)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Blue Ridge Cancer Care

Roanoke, Virginia, 24014, United States

Location

Related Publications (1)

• Rudin CM, Pietanza MC, Bauer TM, Ready N, Morgensztern D, Glisson BS, Byers LA, Johnson ML, Burris HA 3rd, Robert F, Han TH, Bheddah S, Theiss N, Watson S, Mathur D, Vennapusa B, Zayed H, Lally S, Strickland DK, Govindan R, Dylla SJ, Peng SL, Spigel DR; SCRX16-001 investigators. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol. 2017 Jan;18(1):42-51. doi: 10.1016/S1470-2045(16)30565-4. Epub 2016 Dec 5.

  PMID: 27932068 DERIVED

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

rovalpituzumab tesirine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Senior Director, Clinical Operations
• Organization: AbbVie Stemcentrx

isobel.lakatos@abbvie.com

(650) 827-4879

Study Officials

• Donald Strickland, MD

  SCRI Innovations

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2013
• First Posted: July 17, 2013
• Study Start: July 1, 2013
• Primary Completion: November 28, 2016
• Study Completion: November 28, 2016
• Last Updated: August 9, 2018
• Results First Posted: July 11, 2018

Record last verified: 2018-07

Locations

US (8)