Pegzilarginase and Pembrolizumab for Extensive Disease Small Cell Lung Cancer

NCT03371979 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CAEB1102-101B; KEYNOTE PN758
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 22

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.

Conditions

Small-cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• 1. Phase 1: Incidence of treatment-related adverse events as assessed by CTCAE v4.0

  1\. Number of participants experiencing treatment-related adverse events as assessed by CTCAE v4.0.

  Estimated up to 6 months

• Phase 2: Efficacy determined by Objective Response Rate (ORR:CR+PR) per RECIST 1.1.

  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.

  Estimated up to 6 months

Secondary Outcomes (7)

• Objective Response Rate

  At 9, 18, and 27 weeks after first dose and every 12 weeks thereafter up to 24 months

• Clinical Benefit Rate

  At 18 and 27 weeks after first dose and every 12 weeks thereafter up to 24 months

• Time to Response

  At 9, 18, and 27 weeks after first dose and every 12 weeks thereafter up to 24 months

• Duration of Response

  At 18 and 27 weeks after first dose and every 12 weeks thereafter up to 24 months

• Progression free survival

  From first treatment up to 24 months

Study Arms (1)

Pegzilarginase plus Pembrolizumab

EXPERIMENTAL

Phase 1 \& 2

Drug: Pegzilarginase; Drug: Pembrolizumab

Interventions

Pegzilarginase DRUG

Administered IV

Also known as: AEB1102 (Co-ArgI-PEG)

Pegzilarginase plus Pembrolizumab

Pembrolizumab DRUG

Administered IV

Also known as: MK-3475, Keytruda

Pegzilarginase plus Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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 with specimens collected within 10 days prior to day 1 of cycle 1
• 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.

You may not qualify if:

• 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 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
• Has a diagnosis of an immunodeficiency, is receiving systemic steroid therapy (except for physiological dose levels), or immunosuppressive therapies
• 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
• 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
• 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

Sponsors & Collaborators

• Aeglea Biotherapeutics: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (22)

University of Alabama, Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Mid Florida Hematology and Oncology Centers

Orange City, Florida, 32763, United States

Location

Woodlands Medical Specialists, PA

Pensacola, Florida, 32503, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30307, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

The Valley Hospital, Luckow Pavilion

Paramus, New Jersey, 07652, United States

Location

Oncology Hematology Care Inc.

Cincinnati, Ohio, 45242, United States

Location

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Charleston Hematology Oncology Associates

Charleston, South Carolina, 29414, United States

Location

West Clinic

Germantown, Tennessee, 38138, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology-Memorial City

Houston, Texas, 77024, United States

Location

Texas Oncology-Tyler

Tyler, Texas, 75702, United States

Location

Oncology & Hematology Associates of SW Virginia

Blacksburg, Virginia, 24060, United States

Location

Fundacion De Investigacion, Hematology/Oncology

San Juan, 00927, Puerto Rico

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Josie Gayton

  Aeglea Biotherapeutics, Inc.

  STUDY DIRECTOR

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: November 20, 2017
• First Posted: December 13, 2017
• Study Start: December 21, 2017
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: November 4, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (21); PR (1)