Pegzilarginase and Pembrolizumab for Extensive Disease Small Cell Lung Cancer

Status: Active

Description

The main purpose of this Phase 1 / 2 study is to determine the safety and efficacy of pegzilarginase in combination with pembrolizumab in patients with ED-SCLC who have relapsed or progressive disease on or within 6 months of platinum-based chemotherapy.

Eligibility Criteria

Inclusion Criteria

  • Patient is able and willing to provide written informed consent
  • Be > 18 years of age on day of signing informed consent
  • Have histologically or cytologically confirmed SCLC that meets:
  • Extensive disease per criteria of the International Association for the Study of Lung Cancer (IASLC)-American Joint Committee on Cancer (AJCC) TNM staging system
  • Have not tolerated or have progressed or relapsed on or within 6 months of platinum-based chemotherapy
  • Have a performance status of ≤ 1 on the ECOG Performance Scale
  • Have measurable disease based on RECIST 1.1
  • Willing to undergo core needle or incisional biopsy to obtain fresh tumor tissue specimens
  • Demonstrate adequate organ function as evidenced by laboratory testing
  • Female child-bearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication
  • Sexually active male or female must be surgically sterile post-menopausal, or must agree to use a physician-approved method of birth control during the study through a minimum of 120 days after the last study drug administration.

Exclusion Criteria

  • Has received more than 2 platinum-based regimens against SCLC
  • Has received pembrolizumab, or prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody as part of any previous therapy, including trials
  • Has participated in Merck MK-3475 (pembrolizumab) clinical trials
  • Has received pegzilarginase as part of any previous therapy
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency, is receiving systemic steroid therapy (except for physiological dose levels), or immunosuppressive therapies
  • Has a known additional malignancy that is progressing or requires active treatment (Exception: basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer)
  • Has known central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided they are:
  • Stable (without evidence of progression by imaging [using same imaging modality for each assessment] for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline)
  • Have no evidence of new or enlarging brain metastases
  • Are not using steroids for at least 7 days prior to trial treatment
  • Has known carcinomatous meningitis
  • Has an active autoimmune disease requiring systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections will not be excluded from the study. Patients with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
  • Has evidence of interstitial lung disease, history of non-infectious pneumonitis that required steroids, or current pneumonitis
  • Inadequately controlled hypertension (defined as systolic blood pressure ≥ 200 mmHg and/or diastolic blood pressure ≥ 120 mmHg) on more than one occasion in the month before planned day of infusion
  • Currently taking 3 or more anti-hypertensive medications
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac or vascular surgery within 6 months prior to day 1 of study treatment
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has a known history of Human Immunodeficiency Virus (HIV) (positive for HIV p24 antigen or HIV 1/2 antibodies)
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected)
  • Has a known history of active tuberculosis (Bacillus tuberculosis).

Locations & Contacts

Colorado

Aurora
University of Colorado Hospital
Status: Active
Name Not Available

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Jhanelle E. Gray
Phone: 813-745-6895
Email: jhanelle.gray@moffitt.org

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Active
Name Not Available
Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Contact: Siddhartha Devarakonda
Phone: 800-600-3606
Email: info@siteman.wustl.edu

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: In review
Name Not Available

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Aeglea Biotherapeutics

Trial IDs

Primary ID CAEB1102-101B; KEYNOTE PN758
Secondary IDs NCI-2017-02397
Clinicaltrials.gov ID NCT03371979