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Pegzilarginase and Pembrolizumab for Extensive Disease Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT03371979
Recruitment Status : Active, not recruiting
First Posted : December 13, 2017
Last Update Posted : October 7, 2019
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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 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 2020
Estimated Study Completion Date : December 2020

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.



Information from the National Library of Medicine

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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 with specimens collected within 10 days prior to day 1 of cycle 1
  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 a study of an investigational agent or received the last dose of an investigational agent within 4 weeks prior to the first dose of treatment in this study (a shorter interval for kinase inhibitors or other short half-life drugs could be considered after approval from the Sponsor). Is currently participating in a study of an investigational device within 4 weeks of the first dose of treatment
  6. Has a diagnosis of an immunodeficiency, is receiving systemic steroid therapy (except for physiological dose levels), or immunosuppressive therapies
  7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer) that has undergone potentially curative therapy
  8. Has known central nervous system (CNS) metastases. However, patients with previously treated brain metastases may participate provided neurologic symptoms have stabilized, there is no evidence of new brain metastases or hemorrhage and they are not using steroids for brain metastases or for complications derived from their treatment for at least 7 days prior to the first dose of 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)
  20. Has had an allogenic tissue/solid organ transplant.

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


  Hide Study Locations
Locations
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United States, Alabama
University of Alabama, Mitchell Cancer Institute
Mobile, Alabama, United States, 36604
United States, Arizona
Arizona Oncology Associates, PC-HAL
Tempe, Arizona, United States, 85284
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
United States, Florida
Baptist Health Medical Group Oncology LLC
Miami, Florida, United States, 33176
Mid Florida Hematology and Oncology Centers
Orange City, Florida, United States, 32763
Woodlands Medical Specialists, PA
Pensacola, Florida, United States, 32503
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30307
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Cancer Specialists
Omaha, Nebraska, United States, 68130
United States, New Jersey
The Valley Hospital, Luckow Pavilion
Paramus, New Jersey, United States, 07652
United States, Ohio
Oncology Hematology Care Inc.
Cincinnati, Ohio, United States, 45242
United States, Oregon
Providence Cancer Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
UPMC Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Charleston Hematology Oncology Associates
Charleston, South Carolina, United States, 29414
United States, Tennessee
West Clinic
Germantown, Tennessee, United States, 38138
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology-El Paso Cancer Treatment Center Gateway
El Paso, Texas, United States, 79915
Texas Oncology-Memorial City
Houston, Texas, United States, 77024
Texas Oncology-McAllen South Second Street
McAllen, Texas, United States, 78503
Texas Oncology-Tyler
Tyler, Texas, United States, 75702
United States, Virginia
Oncology & Hematology Associates of SW Virginia
Blacksburg, Virginia, United States, 24060
United States, Washington
Northwest Cancer Specialists, PC
Vancouver, Washington, United States, 98684
Puerto Rico
Fundacion De Investigacion, Hematology/Oncology
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Aeglea Biotherapeutics
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Jim Joffrion Aeglea Biotherapeutics, Inc.

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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: October 7, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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, Immunological
Antineoplastic Agents