Clinical trial NCT01901653: Rovalpituzumab Tesirine (SC16LD6.5) in Recurrent Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Recurrent Small Cell Lung Cancer
Keywords: Small cell lung cancer
Lead sponsor: Stemcentrx
Sponsor class: INDUSTRY
First posted: 2013-07-17
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria

1. Provision of informed consent
2. Male or female ≥18 years of age
3. Histologic or cytologic confirmed diagnosis of small cell lung cancer, either limited or extensive disease at initial presentation is allowed
4. 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
5. Measurable disease (only for the phase II portion)
6. Eastern Cooperative Oncology Group (ECOG) Performance status 0-1
7. A minimum life expectancy of 12 weeks
8. 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
   * Aspartate aminotransferase (AST)/Alanine transferase (ALT) (SGOT/SGPT) \< 2.5 x ULN for the reference laboratory or \< 5 x ULN in the presence of liver metastases
   * Serum creatinine \< 1.5 x ULN
9. No 'active' CNS metastases. Prior CNS metastases are allowed, provided adequate palliative therapy has been administered and CNS disease control has been established prior to study entry.

   • A brain MRI scan, ≤ 28 days from day 1, is required
10. Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures and who have a negative serum pregnancy test within 1 week prior to initial study treatment. (See Appendix B)
11. Male patients willing to use adequate contraceptive. (See Appendix B)
12. At least 21 days must have elapsed prior to day 1 cycle 1, from chemotherapy, radiotherapy, immunotherapy or following major surgery and any surgical incision should be completely healed. At least 14 days must have elapsed prior to Day 1 Cycle 1 for "limited palliative radiotherapy", defined as a course of therapy encompassing \< 25% total bone marrow volume and not exceeding 30 Gy.
13. At least 14 days must have elapsed for chemotherapy regimens, biologic, and targeted therapy given continuously or on a weekly basis with limited potential for delayed toxicity.

Exclusion Criteria:

1. Patients who are pregnant or breastfeeding.
2. Active involvement of the Central Nervous System (CNS).
3. Uncontrolled infection or systemic disease.
4. 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.
5. 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.
6. 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.
7. Known hypersensitivity to any components of SC16LD6.5 study drug product.
8. 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.
9. Psychiatric disorder or social or geographic situation that would preclude study participation.
10. QT interval measurement corrected by Fridericia's formula (QTcF) interval of \>450 msec (males) or \>470 msec (females)

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Rovalpituzumab Tesirine
timeFrame: 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:
measure: Objective Response Rate (ORR)
timeFrame: From first dose of rovalpituzumab tesirine to last event, up through study completion (on average approximately 4 months).
measure: Duration of Response (DOR)
timeFrame: 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).
measure: Clinical Benefit Rate (CBR)
timeFrame: From first dose of Rovalpituzumab tesirine to last event timepoint, up through study completion (on avergae approximately 4 months).
measure: Progression-free Survival (PFS)
timeFrame: 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).
measure: Overall Survival
timeFrame: 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).
measure: Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine Antibody Drug Conjugate (ADC)
timeFrame: From Day 1 of first dose to End of Dose Cycle
measure: Area Under the Serum Concentration-time Curve (AUC) of Rovalpituzumab Tesirine ADC
timeFrame: From Day 1 of first dose to End of Dose Cycle
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
Study officials:
affiliation: SCRI Innovations
name: Donald Strickland, MD
role: STUDY_DIRECTOR
References:
citation: 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.