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Pegzilarginase and Pembrolizumab for Extensive Disease Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT03371979
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : April 27, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Aeglea Biotherapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Small-cell Lung Cancer Drug: Pegzilarginase Drug: Pembrolizumab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Pegzilarginase (AEB1102, Co-ArgI-PEG) in Combination With Pembrolizumab in the Treatment of Patients With Extensive Disease (ED) Small Cell Lung Cancer (SCLC)
Actual Study Start Date : December 21, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Pegzilarginase plus Pembrolizumab
Phase 1 & 2
Drug: Pegzilarginase
Administered IV
Other Name: AEB1102 (Co-ArgI-PEG)

Drug: Pembrolizumab
Administered IV
Other Names:
  • MK-3475
  • Keytruda




Primary Outcome Measures :
  1. 1. Phase 1: Incidence of treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Estimated up to 6 months ]
    1. Number of participants experiencing treatment-related adverse events as assessed by CTCAE v4.0.

  2. Phase 2: Efficacy determined by Objective Response Rate (ORR:CR+PR) per RECIST 1.1. [ Time Frame: Estimated up to 6 months ]

    1. Objective Response Rate (ORR:) per RECIST 1.1

    • The Objective Response Rate (ORR) is defined as the percentage of subjects whose best objective response (BOR) is either complete response (CR) or partial response (PR). The ORR will be derived from the BOR according to response evaluation criteria in solid tumors (RECIST) v1.1 as assessed by the Investigator.



Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: At 9, 18, and 27 weeks after first dose and every 12 weeks thereafter up to 24 months ]
    Percentage of patients whose cancer achieves either complete response (CR) or partial response (PR).

  2. Clinical Benefit Rate [ Time Frame: At 18 and 27 weeks after first dose and every 12 weeks thereafter up to 24 months ]
    Percentage of patients who have achieved CR, PR or Stable Disease (SD), lasting at least 8 weeks.

  3. Time to Response [ Time Frame: At 9, 18, and 27 weeks after first dose and every 12 weeks thereafter up to 24 months ]
    Time (weeks) from first treatment to the first documented CR or PR.

  4. Duration of Response [ Time Frame: At 18 and 27 weeks after first dose and every 12 weeks thereafter up to 24 months ]
    Time (weeks) from first documented CR or PR, until disease progression (PD).

  5. Progression free survival [ Time Frame: From first treatment up to 24 months ]
    Time (weeks) from first treatment to first observation of PD or death from any cause.

  6. Overall Survival [ Time Frame: From first treatment up to 24 months ]
    Time (weeks) from first treatment to death due to any cause.

  7. Phase 2: Incidence of treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: From first treatment up to 24 months ]
    Number of participants experiencing treatment-related adverse events as assessed by CTCAE v4.0.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Patient is able and willing to provide written informed consent
  2. Be > 18 years of age on day of signing informed consent
  3. Have histologically or cytologically confirmed SCLC that meets:

    1. Extensive disease per criteria of the International Association for the Study of Lung Cancer (IASLC)-American Joint Committee on Cancer (AJCC) TNM staging system
    2. Have not tolerated or have progressed or relapsed on or within 6 months of platinum-based chemotherapy
  4. Have a performance status of ≤ 1 on the ECOG Performance Scale
  5. Have measurable disease based on RECIST 1.1
  6. Willing to undergo core needle or incisional biopsy to obtain fresh tumor tissue specimens
  7. Demonstrate adequate organ function as evidenced by laboratory testing
  8. 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
  9. 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.

Key Exclusion Criteria:

  1. Has received more than 2 platinum-based regimens against SCLC
  2. 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
  3. Has participated in Merck MK-3475 (pembrolizumab) clinical trials
  4. Has received pegzilarginase as part of any previous therapy
  5. 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
  6. Has a diagnosis of immunodeficiency, is receiving systemic steroid therapy (except for physiological dose levels), or immunosuppressive therapies
  7. 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)
  8. Has known central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided they are:

    1. 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)
    2. Have no evidence of new or enlarging brain metastases
    3. Are not using steroids for at least 7 days prior to trial treatment
  9. Has known carcinomatous meningitis
  10. 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
  11. Has evidence of interstitial lung disease, history of non-infectious pneumonitis that required steroids, or current pneumonitis
  12. 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
  13. Currently taking 3 or more anti-hypertensive medications
  14. Prior history of hypertensive crisis or hypertensive encephalopathy
  15. 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
  16. 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
  17. Has a known history of Human Immunodeficiency Virus (HIV) (positive for HIV p24 antigen or HIV 1/2 antibodies)
  18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected)
  19. Has a known history of active tuberculosis (Bacillus tuberculosis).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03371979


Contacts
Contact: Aeglea Clinical Department 1.855.509.9921 oncology@aegleabio.com

Locations
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30307
Contact: Taofeek Owonikoko, MD         
Principal Investigator: Taofeek Owonikoko, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Shirish Gadgeel, MD         
Principal Investigator: Shirish Gadgeel, MD         
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Hirva Mamdani, MD         
Principal Investigator: Hirva Mamdani, MD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Siddartha Devarakonda, MD         
Principal Investigator: Siddartha Devarakonda, MD         
United States, Oregon
Providence Cancer Center Recruiting
Portland, Oregon, United States, 97213
Contact: Rachel Sanborn, MD         
Principal Investigator: Rachel Sanborn, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: David Spigel, MD         
Principal Investigator: David Spigel, MD         
Puerto Rico
Fundacion De Investigacion, Hematology/Oncology Recruiting
San Juan, Puerto Rico, 00927
Contact: Mirelis Acosta-Rivera, MD         
Principal Investigator: Mirelis Acosta-Rivera, MD         
Sponsors and Collaborators
Aeglea Biotherapeutics
Merck Sharp & Dohme Corp.
Investigators
Study Director: Jim Joffrion Aeglea Biotherapeutics, Inc.

Responsible Party: Aeglea Biotherapeutics
ClinicalTrials.gov Identifier: NCT03371979     History of Changes
Other Study ID Numbers: CAEB1102-101B; KEYNOTE PN758
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: April 27, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents